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Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015



This is the sixth special report that the European Society for Blood and Marrow Transplantation regularly publishes on the current practice and indications for haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred in the field of haematopoietic SCT over the last years. Cord blood units as well as haploidentical donors have been increasingly used as stem cell sources for allo-SCT, thus, augmenting the possibility of finding a suitable donor for a patient. Continuous refinement of conditioning strategies has also expanded not only the number of potential indications but also has permitted consideration of older patients or those with co-morbidity for a transplant. There is accumulating evidence of the role of haematopoietic SCT in non-haematological disorders such as autoimmune diseases. On the other hand, the advent of new drugs and very effective targeted therapy has challenged the role of SCT in some instances or at least, modified its position in the treatment armamentarium of a given patient. An updated report with revised tables and operating definitions is presented.


This report is the sixth report from the European Society for Blood and Marrow Transplantation (EBMT) classifying allogeneic and autologous haematopoietic SCT (HSCT) procedures according to prevailing clinical practice in Europe.1, 2, 3, 4, 5 Since the first report, major changes have occurred in clinical practice based on new scientific and technical developments. This includes the recognition of new indications but also changed indications for HSCT based on important developments in results of HSCT in non-haematological malignancies, including autoimmune diseases, and on novel non-transplant treatment strategies of haematological and non-haematological malignancies. New strategies based on cord blood stem cells (CB) or haploidentical donors have significantly expanded the accessibility of allo-SCT (allo-HSCT) approaches. Limitations for the transplant procedures such as age and co-morbidities have been modified because of the introduction of reduced-intensity conditioning (RIC) regimens. The updated proposed indications are presented in Tables 1 and 2. As in the previous reports, we have attempted to summarize the opinions and practice of clinicians working in transplant centres in Europe in 2015. The EBMT recommendations are based on existing prospective clinical trials, registry data and expert opinion, but not on a formal extensive review of the literature. Therefore, some recommendations have been made based upon analogy, inference and expertise. Each section of the recommendations has been discussed within the appropriate working party of the EBMT. The EBMT recommendations are not meant to decide for an individual patient whether a transplant is the correct choice of procedure. It is also outside the scope of this report to classify indications based on the use of a particular conditioning regimen or a particular stem cell source. The classifications are aimed to give guidance and have to be considered together with the risk of the disease, the risk of the transplant procedure and the results of non-transplant strategies. When the recommendations are interpreted, it is important, besides a possible survival gain, to assess issues of quality of life and late effects into the risk assessment strategy. Such effects are especially important in children and adolescents.

Table 1 Proposed classification of transplant procedures for adults—2015
Table 2 Proposed classification of transplant procedures for children—2015


Haematopoietic stem cell transplant (HSCT)

HSCT refers to any procedure where haematopoietic stem cells of any donor type and any source are given to a recipient with the intention of repopulating and replacing the haematopoietic system in total or in part. Stem cells can be derived from BM, PB or CB. The goal of the procedure should be defined beforehand and a documented informed consent of the patient (and donor) obtained before the procedure.

Donor categories

Donor type is categorized as autologous, syngeneic, HLA-identical sibling donor, other family donor or unrelated donor. A well-matched unrelated donor (MUD) is defined as a 10/10 or 8/8 identical donor based on HLA high-resolution typing for class I (HLA-A, -B, -C) and II (HLA-DRB1, -DQB1). A mis-matched unrelated donor (MMUD) refers to an adult unrelated donor mismatched in at least one Ag or allele at HLA-A, -B, -C or –DR.6 There is growing evidence that not all HLA mismatches are created equal. Permissive HLA mismatches seem to confer similar transplant-related outcomes when compared with matched donor sources, presumably reflecting the inability of the T cell to recognize an intrinsic HLA sequence difference.7 A non-permissive HLA allele mismatch combination leads to a poorer outcome.8, 9, 10 MUD transplants increase donor availability but take time to organize because of donor screening and graft retrieval.

A haploidentical donor is defined as a family member where only one HLA haplotype is genetically identical with the patient. The advantages of transplantation from a haploidentical donor include the availability for almost all patients, choice of best donor from a panel of candidate family members, no undue delay in obtaining the graft and easy access to donor-derived cellular therapies if needed after the SCT procedure. Major drawbacks used to be the very strong graft-vs-host and host-vs-graft alloresponses11 with a high incidence of severe GVHD and graft rejection after the HSCT. From the 1980s onwards, attempts to overcome the HLA barrier focused on strengthening myeloablation and immunosuppression in the conditioning regimen12, 13 or on partially depleting the graft of T cells using anti-thymocyte globulin or the T10B9 monoclonal Ab in conjunction with in vivo immunotoxin14 and with post-transplantation CY and steroids. A major advance came with strategies comprising myeloablative conditioning based on TBI followed by transplantation of a mega-dose of extensively T-cell-depleted mobilized PBSC. This ensured a high engraftment rate in the absence of GVHD and has given similarly good results in both children and adults with high-risk acute leukaemia than MUD HSCT.15, 16, 17, 18, 19 In recent years, interest in T-cell-replete full haplotype-mismatched HSCT was reawakened by new strategies for GVHD prophylaxis. The use of high-dose post-transplantation CY to prevent graft rejection and GVHD after nonmyeloablative conditioning and T-cell-replete BM transplantation has been extensively pioneered by the Baltimore and Seattle groups and has given promising results in terms of PFS and OS in particular in patients with lymphoid malignancies with acceptable rates of graft failure, GVHD and non-relapse mortality (NRM).20, 21, 22

International registries often lack complete information on HLA typing reports of unrelated donor transplants. To understand the impact of incomplete HLA characterization, the Center for International Blood and Marrow Transplant Research (CIBMTR)23 analysed 14 797 unrelated donor HSCT (1995–2006) using multivariable regression modelling adjusting for factors affecting survival and identified three groups with significantly different outcomes; well-matched cases had either no identified HLA mismatch and informative data at 4 loci or allele matching at HLA-A, -B and -DRB1, partially matched pairs had a defined, single-locus mismatch and/or missing HLA data, and mismatched cases had 2 allele or Ag mismatches. Multivariate 5-year survival estimates were significantly different for the previously established groups of patients and the authors suggested that these proposed HLA sub-groupings could be used when complete HLA typing was not available. Furthermore, this improved categorization of HLA matching status could standardize interpretations of prior unrelated donor HSCT experience. This classification should only be used for retrospective analysis purposes but not to prospectively classify the degree of mismatching between a given donor and patient.

Stem cell sources

There are three commonly used sources of haematopoietic stem cells: BM, cytokine-mobilized PB progenitor cells (PBSC), and CB cells.

For autologous HSCT (auto-HSCT), PBSC is the preferred choice because of a more rapid haematopoietic reconstitution. In cases of insufficient mobilization with G-CSF-based regimens, in many patients, an adequate harvest can be achieved with the use of inhibitors of the interaction between CX chemokine receptor 4 (CXCR4) and stromal derived factor-1 alpha (SDF-1), such as plerixafor.24, 25, 26 For allo-HSCT, all three stem cell sources are used and have their specific advantages and disadvantages. PBSCs are associated with more rapid engraftment but are associated also with an increased risk of chronic GVHD compared with BM.27 The higher risk for chronic GVHD might therefore make PB HSCT a less attractive option for children, or for some patients with early stage disease. In some countries, it is prohibited to give G-CSF to donors who are <18 years old. Furthermore, the additional graft-vs-malignancy effect seen in patients with chronic GVHD is not applicable for patients with non-malignant conditions such as severe aplastic anaemia (SAA). BM is therefore seen as the preferred choice in SAA when using ATG-based conditioning regimens.28, 29 The donor’s preferences must also be taken into account as there are differences in the side effects experienced by the donors from a BM or PBSC harvest.

Unrelated CB cells are commonly used when patients lack an HLA-identical sibling or a MUD. An additional advantage is that CB cells can be obtained rapidly and may therefore be a better option when a patient needs an urgent HSCT. The indications for the use of CB as a source for stem cells in children are identical to the indications listed in Table 2 for MUD transplants. CB units should be selected by HLA matching and cell dose. The most important factor influencing outcome is the cell dose and a minimum dose of 2.5–3 × 107 nucleated cells/kg body weight of recipient at collection or 2 × 107 nucleated cells/kg at infusion is recommended; a higher dose of >4 × 107 nucleated cells/kg is needed for SAA patients. HLA disparity should not exceed two of six defined by HLA-A, -B Ag and HLA-DRB1 allele typing. According to registry analyses, outcomes of unrelated CB HSCT in children and adults with acute leukaemia are comparable with MUD BM transplants.30, 31 In adults with relapsed/refractory lymphoproliferative disorders, unrelated CB HSCT achieves comparable outcomes than those of RIC unrelated HSCT.32

To overcome the cell-dose limitation, Barker et al.33 pioneered the use of double cord blood transplant, sequentially infusing 2 CB units instead of 1. The results were encouraging, with all patients engrafting neutrophils in a median of 23 days (range, 15–41). The requirements of cell dose and number of HLA disparities for the double units are the same as for single units. Thus, no more than two of six HLA disparities should exist between each CB unit and the patient. Interestingly, the incidence of acute GVHD seems to be higher after double cord blood transplant although this fact does not impact on NRM34 and the relapse rate is lower35 in comparison with a single unit cord blood transplant. A registry analysis suggested that in patients with acute leukaemia being allografted with a myeloablative conditioning regimen, double cord blood transplant seems to be a associated to a lower relapse rate in comparison with matched related donors, MUD and 1-Ag MMUD although NRM is higher, thus rendering no significant differences in terms of leukaemia-free survival (LFS), supporting the use of two partially HLA-matched CB units when patients lack an HLA-matched donor.36 Several single centre and retrospective analysis support the use of RIC regimens in the setting of cord blood transplant.37, 38, 39, 40

Combined transplantation of a single CB unit with CD34+ stem cells from a HLA-mismatched auxiliary donor (haplo-cord) reliably reduces the time to neutrophil engraftment, in comparison with other CB strategies, to approximately day +12.41, 42, 43 In addition, haplo-cord provides comparable overall outcomes to other donor sources while allowing the use of single CB units with relatively low cell content, and expands donor availability reducing CB cell dose requirements.

Nowadays, and with a patient being a potential candidate for an allo-HSCT who lacks a HLA well-matched donor (HLA identical sibling/MUD), physicians are faced with the need to select amongst different options: MMUD, CB or haploidentical transplants. Despite the large number of phase II and observational studies, the dearth of randomized trials makes the prioritization of an alternative donor difficult and the decision may in part reflect the research agenda of the transplantation centre because no one source of stem cells is clearly superior to another. If a donor is urgently required, CB and haploidentical transplantation have the advantage over adult volunteer MMUD. If upfront costs are a concern, haploidentical family members have a clear advantage over CB and MMUD. For patients with prior infectious problems, CB may be the less desirable stem cell source because of the delayed haematopoietic recovery and immune reconstitution. Finally, not all mismatches in the MMUD setting are equal.

Reduced intensity conditioning (RIC) regimens

The hypothesis that graft-vs-tumour effects are capable of eradicating malignant disorders led to the development of RIC regimens that made allo-HSCT an accessible therapeutic option for older and medically infirm patients who previously were not considered candidates for high-dose conditioning. Not even nowadays, has full consensus on how to define a RIC regimen been achieved by the HSCT community. The EBMT definition considers that any regimen with 50% or less equivalence to a standard conditioning regimen is considered reduced intensity. This includes not only the 50% reduction of the total dose of a given drug (or TBI), but also the use of a single drug in a standard dose but without other drugs (or TBI) usually included in the standard protocol ( RIC regimens are being increasingly used in the last years and represent more than 70% of all transplantation procedures in some disease categories. Most of these regimens have been evaluated in phase 1 or 2 trials only, but there is a paucity of randomized phase 3 trials in the field.

Retrospective registry-based studies comparing myeloablative conditioning protocols with RIC regimens44, 45, 46 indicate that the latter are associated with a lower NRM but with a higher relapse rate after the procedure thus, not significantly modifying long-term outcome of these patients both in terms of PFS and OS. In children with AML, NRM, relapse rate, PFS and OS were not significantly different between myeloablative protocols and RIC regimens.47 In refractory/relapsed Hodgkin lymphoma (HL), children and adolescents had a better PFS because of a higher relapse rate after a RIC-allo that was not accompanied by a higher NRM in the myeloablative setting.48 A randomized prospective clinical trial performed in young patients with AML in first remission49 indicates that RIC regimens result in a similar incidence of NRM and reduced toxic effects compared with standard conditioning without affecting survival outcomes, and thus could be preferentially used in this setting. The role of reduced intensity is yet to be defined in the younger population of patients and additional prospective clinical trials are needed.

Risk factors for outcome

The initial analysis performed by Gratwohl50 indicated that the main risk factors for outcome after HSCT were the stage of the disease, the age of the patient, the time interval from diagnosis to transplant and, for allo-HSCT, the donor/recipient histocompatibility and the donor/recipient sex combination (EBMT score). NRM increases and survival rates decrease with advanced disease stage, increasing age, increasing time from diagnosis to transplant, increase in HLA disparities, and for male recipients having a female donor. All components should be integrated into the risk assessment and the decision making for a transplant. In the case of transplant for non-malignant diseases, such as for autoimmune disorders, NRM and PFS were shown to vary according to original diseases, centre activity and conditioning.51, 52, 53 More recently and with the development of non-myeloablative regimens and improvements in the supportive care after myeloablative protocols, more patients with co-morbidities are being offered allo-HSCT. Investigators from the Fred Hutchinson Cancer Research Center in Seattle developed the HSCT-specific co-morbidity index (HCT—CI) that integrates chronic medical conditions, which are important in predicting NRM in HSCT patients, thus producing a new scoring system that also assesses survival probabilities after allo-HSCT.54 Further refinement of this HCT-CI indicates that Karnofsky status at transplantation is an independent prognostic factor,55 that HCT-CI is predictive of survival across different haematological malignancies56, 57, 58 and that, as expected, age is a poor prognostic factor with a bigger negative impact in those patients with higher HCT-CI.59 Patients without co-morbidities usually tolerate non-myeloablative and myeloablative conditioning regimens equally well, whereas those with co-morbidities (whether young or old) have better survival after RIC protocols. The calculation of the transplantation-associated risk in a given patient is of capital importance nowadays taking into consideration the fair competition existing between a potentially curative but more toxic treatment approach (for example, HSCT) and a non-curative but less toxic and better-tolerated strategy (for example, targeted therapy).

The impact of a quality system on the outcome of HSCT

JACIE (Joint Accreditation Committee of ISCT Europe and EBMT) was started in Europe at the end of the 1990s. JACIE pursues improving the outcome of HSCT by doing it within a standardized and approved quality management system. There is increasing evidence that adherence to standardized quality management policies within an accredited program improves the outcome of allo-HSCT.60, 61

Categorization of transplant procedures

An important aim of the EBMT indication documents has been to classify indications and to give advice about the settings where these types of transplants ought to be performed. These have been classified as ‘standard of care’, ‘clinical option’, ‘developmental’ or ‘generally not recommended’.

Standard of care (S)

Indications categorised as ‘standard of care’ are reasonably well defined and results compare favourably (or are superior) to those of non-transplant treatment approaches. Obviously, defining an indication as the standard of care does not mean an HSCT is necessarily the optimal therapy for a given patient in all clinical circumstances. ‘Standard of care’ transplants may be performed in a specialist centre with experience with HSCT procedures and an appropriate infrastructure as defined by the JACIE guidelines.

Clinical option (CO)

The Clinical Option (CO) category is based on the fact that, for many indications, the number of patients will be low and therefore randomized studies comparing conventional treatment and HSCT are difficult to perform. Results of small patient cohorts treated for this disease by HSCT show efficacy and acceptable toxicities of the procedure. The broad range of available transplant techniques combined with the variation of patient factors such as age and co-morbidity makes interpretation of these data difficult. Our current interpretation of existing data for indications placed in this category supports HSCT as a valuable option for individual patients after careful discussions of risks and benefits with the patient but the value of HSCT needs further evaluation for groups of patients. Transplants for indications under this heading should be performed in a specialist centre with major experience with HSCT procedures, with an appropriate infrastructure as defined by JACIE guidelines.

Developmental (D)

Indications have been classified as developmental if there is limited experience with this indication in combination with the type of transplant and when additional research is needed to define the role of HSCT. These transplants should be done within the framework of a clinical protocol. Such a protocol can either be a randomized comparison of two or more approaches to treatment or a small pilot series undertaken by transplant units with acknowledged expertise in the management of that particular disease or that type of HSCT. The category also covers fundamentally new approaches to the management of a disease that, in a different stage, may already be classified under the standard of care or clinical option. Protocols for ‘developmental’ transplants will have been approved by local research ethics committees and must comply with current international standards. Rare indications where formal clinical trials are not possible should be performed within the framework of a structured registry analysis, ideally an EBMT non-interventional/observational study. It is implied that the results of the study are intended for presentation to and/or publication for the medical community at large. Centres performing transplants under the category of ‘developmental’ should meet JACIE standards. The document for Rules and Regulations for EBMT Clinical Trials could also be used as a guideline (

Generally not recommended (GNR)

The GNR category can include early disease stages when results of conventional treatment do not normally justify the additional risk of NRM, or when the disease is so advanced that the chance of success is so small that the risk of the harvest procedure for the normal donor is difficult to justify. GNR may not apply to specific situations where a syngeneic donor exists. This category also includes HSCT for a disease in a phase or status in which patients are conventionally not treated by HSCT. Therefore, there will be some overlap between GNR and D, and further research might be warranted within prospective clinical studies for some of these indications. GNR does not exclude that centres with a focus on a certain disease can investigate HSCT in these situations.

Data reporting

Reporting of transplant data is mandatory for EBMT members and the minimum amount of data to be reported is contained in the MED-A form. To fully assess the impact of certain transplant strategies for specific indications, reporting of data on a larger case record form (MED-B data) is encouraged.

Evidence grading

There has been no attempt to perform a formal evidence review as the basis for the indication classification but a broad classification has been made as described below. In this classification, results from other therapeutic strategies than HSCT have also been taken into account.

  1. 1

    Evidence from at least one well-executed randomized trial

  2. 2

    Evidence from at least one well-designed clinical trial without randomization; cohort or case-controlled analytic studies (preferably from more than one centre); multiple time-series studies; or dramatic results from uncontrolled experiments

  3. 3

    Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports from expert committees.

Status of transplants in specific diseases in adults

The updated classification of HSCT procedures in adults is shown in Table 1.

Acute myeloid leukaemia (AML)

Adult patients with AML should always be considered for a HSCT, either allo-HSCT or auto-HSCT. Progress has been made with the two modalities in the recent years so that previous guidelines necessitate updating. Patients with good prognosis AML by cytogenetics/molecular markers such as patients with core binding factor leukaemia (t(8;21), inv(16) or t(16;16)), patients with mono- and even biallelic gene mutation in the CCAAT/enhancer binding protein α gene (CEBPA), and patients with mutation in NPM1 but no FlT3ITTD for whom any transplant in first CR (CR1) was previously not recommended should now be evaluated for consolidation with an auto-HSCT in CR1 if in molecular remission with no marker detectable in the leukapheresis products; or for an allogeneic transplant with an HLA identical sibling but not with an alternative donor. These recommendations come from numerous reports, including studies of the EBMT,62 and the meta-analysis of several randomized studies63 on 2983 patients analysed for CEBPA mutational status, which showed that relapse-free survival was significantly superior in patients receiving an allo-HSCT or an auto-HSCT in CR1 as compared with chemotherapy (P<0.001), with a trend for a better OS (P<0.12). As confirmation is still needed, auto- and allo-HSCT with a genoidentical donor in these patients is at present a CO, awaiting classification as standard of care.

Patients in CR1 but clinically slow responders (needing more than one course of induction to achieve CR1, or as a surrogate marker an interval from diagnosis greater than 40 days), and/or with other poor prognosis indicators such as M5 or M6 by FAB classification, poor cytogenetics defined as a complex karyotype (more than three abnormalities) or monosomy 7, inv(3)(q21q26), t(6;11)(q27;q23), t(6;9)(p23;q34) or t(11;19)(q23;p13.1)64 and/or those with the FLT3ITD or MLL molecular mutation, should be allografted with the best available donor including genoidentical family members, unrelated donors, CB and haploidentical donors, as part of a standard of care approach; auto-HSCT is not recommended.

All other patients in CR1 with other cytogenetic abnormalities or normal karyotype belonging to the intermediate risk category are candidates for all kinds of HSCT from a well HLA-matched related or unrelated donor. Auto-HSCT has recently regained interest, thanks to several improvements such as reduced NRM with the introduction of IV BU in the pre-transplant regimen,65 better monitoring of MRD by immunophenotyping66 and molecular biology such as WT1 overexpression67 and, possibly, with the introduction of maintenance therapy post autologous transplantation.68 Analyses of other molecular markers as indicators of AML subsets with distinct prognosis are increasingly being used for decision purposes, but are still under validation.69, 70 At the present time, some therapeutic trials evaluate risk-adapted and MRD-directed transplant strategies where MRD-negative patients are autografted and MRD-positive patients allografted. In these patients, allo-HSCT is standard of care and auto-HSCT remains a clinical option waiting for further assessment. However, although there are considerable data showing better outcome of allo-HSCT with genoidentical donors over auto-HSCT, there are no such data when comparing auto-HSCT to allogeneic transplantation with alternative donors. In addition to that, the quality of life is better after an autologous than an allogeneic transplant.71 Therefore, in MRD-negative patients, auto-HSCT is a clinical option while waiting for results of randomized studies, to possibly reach an upgrade in the categorization of transplant procedure. A recent retrospective study from CIBMTR72 has concluded that in the absence of a matched sibling donor, auto-HSCT may provide an acceptable alternative post-remission therapy for patients with AML in CR1.

Patients with AML 3 achieving CR2 and MRD negativity should be autografted (S), because the outcome is similar or better than after allogeneic transplantation.73, 74, 75

Acute lymphoid leukaemia (ALL)

The field of HSCT in adult ALL remains controversial. The introduction of more aggressive chemotherapy regimens from the models developed in children to adolescents and young adults has reduced the need for allogeneic transplantation in most patients younger than 35 years of age. In contrast, allo-HSCT remains the standard of care in high-risk patients such as slow remitters or steroid and/or chemotherapy-resistant patients, patients over 35 years of age and all patients following relapse post CR1. Regarding standard risk patients, a recent randomized study comparing the outcome of 433 adult ALL patients, according to a sibling donor vs no-donor comparison has resulted in a LFS at 5 years significantly better in the donor group: 60 vs 42% (hazard ratio: 0.60; P=0.01).76, 77

In a large EBMT retrospective study performed in 200378 on a total of 1402 patients allografted from 1990 to 2000 with a genoidentical donor, it was possible to identify three prognostic groups based on three prognostic factors: age (below and over 35 years), response to induction (rapid and slow remitters) and donor sex. Group 1 (good prognosis) included patients aged <35 years old, achieving CR1 with one induction course and to be transplanted with any other sex combination than female to male (score 0), group 2 (intermediate) with one adverse factor (score 1) and group 3 (bad prognosis) with two or three adverse criteria (scores 2 and 3). The 3-year LFS was 56%, 48% and 29% and the OS was 65%, 53% and 29%, respectively. Some recent studies have readdressed the question of auto-HSCT: for instance, a meta-analysis using data from 13 studies including 2962 patients,79 excluding Philadelphia chromosome-positive (Ph pos) patients, showed a survival benefit for those patients having a matched sibling donor and for patients younger than 35 years of age (OR=0.79, P=0.0003) but not for older ones (OR=1.01, P=0.9) because of the higher absolute risk of NRM for older patients. No beneficial effect of autografting was seen compared with chemotherapy in this analysis.

In this context, the place of autologous transplant is difficult to assess. In patients over the age of 55, a very recent retrospective EBMT study (Giebel S, personal communication) on 267 patients treated with a RIC-allo and 179 patients autografted in CR1, showed better results for auto-HSCT, with a probability of OS at 2 years of 44% for RIC-allo and 57% for auto-HSCT (P=0.02), owing to a significantly reduced NRM for auto-HSCT (23% vs 11%, respectively, P=0.002).

In Ph pos patients, a recent EBMT retrospective study80 indicates that results of auto-HSCT have significantly improved over time: the probability of OS at 3 years increased from 16% for transplants performed between 1996 and 2001 to 48% between 2002 and 2006 and 57% between 2007 and 2010 (P<0.0001); LFS was 11%, 39% and 52%, respectively (P<0.0001). Relapse incidence decreased from 70 to 45% and 45% (P=0.01), respectively, while NRM was 19%, 15% and 3% (P=0.08). In a multivariate analysis, year of auto-HSCT was the only independent factor influencing the risk of treatment failure (hazard ratio=0.37; P<0.001). In a subgroup of 22 patients treated with tyrosine kinase inhibitors (TKI) and being in complete molecular remission at the time of the autologous transplant, the LFS rate at 3 years was 65%. Data have been accumulated over time indicating that auto-HSCT at the time of MRD negativity obtained with the contribution of TKI is associated with good outcomes.

Adults with ALL with persistent or relapsing MRD are candidates for allo-HSCT in CR1 from either an HLA-identical sibling or an unrelated donor. Allo-HSCT for standard risk patients in CR1 should be performed whenever possible within a clinical protocol. Patients relapsing after chemotherapy and achieving CR2 are candidates for allo-HSCT from an HLA-identical sibling, an unrelated donor or other alternative donors such as CB or haploidentical donor. For patients with either Ph pos or Ph negative (Ph neg) ALL with negative MRD status, auto-HSCT is a clinical option. The role of maintenance therapy post autologous transplant remains unknown despite old favourable reports.81

Chronic myeloid leukaemia (CML)

HSCT remains the only curative treatment for CML. However, after the advent of TKI, allo-HSCT cannot be recommended to all patients with a suitable donor as first-line treatment after diagnosis. Imatinib should be the first-line therapy for all patients in chronic phase. Some patients in molecular remission after treatment with imatinib have remained in molecular remission for a median of 24 months after cessation of the drug.82 Patients with suboptimal response or failure to first-line therapy according to the European Leukaemia Net (ELN) guidelines should start a search for a suitable donor as early as possible (sibling or unrelated). They should receive treatment with second line TKI and are candidates to proceed to HSCT in optimal response as soon as possible if their EBMT risk score is 0–1 or in case of a prior loss of cytogenetic or haematological response to imatinib if their EBMT risk score is 0–4. If there is no haematological response to second line treatment, patients are candidates for allo-HSCT on any EBMT risk score (these patients may benefit from treatment with third line TKI prior to HSCT depending on ABL mutation analysis). Patients with ABL mutations known to be resistant to second generation TKI are candidates to undergo HSCT if their EBMT risk score is 0–4 after failing imatinib.

Patients in advanced phase referred for a HSCT could have therapy with TKI or intensive therapy±TKI as preparation for HSCT. HSCT should be performed as soon as possible after achieving second chronic phase without the need to achieve deep cytogenetic or molecular responses. Patients in second chronic phase are candidates for allo-HSCT from an HLA-identical sibling, an unrelated donor, or other alternative donors such as CB or haploidentical family donor. A patient with a syngeneic donor is always a candidate for a HSCT with standard conditioning. Auto-HSCT should only be recommended in the context of clinical studies.

Myeloproliferative disorders other than CML

Allo-HSCT is today the only curative option for patients with myeloproliferative disorders. Polycythaemia vera and essential thrombocythaemia are, in general, not indications for allo-HSCT unless the disease has progressed to myelofibrosis or secondary leukaemia.83

Owing to the lack of alternative therapeutic options, allo-HSCT is a reasonable treatment for primary myelofibrosis with intermediate II and high risk according to the Dynamic International Prognostic Index (DIPSS). Myelofibrosis post-essential thrombocythaemia or -polycythaemia vera and should also be considered an indication for allo-HSCT for all patients younger than 65 years of age.84 In younger patients, transplantation in intermediate I is justified in individual cases. The experience of allo-HSCT with low-risk DIPSS is limited and remains controversial. The available data do not support splenectomy prior to HSCT. The introduction of JAK inhibitors in the treatment of myelofibrosis may help to improve constitutional symptoms and to reduce spleen size before transplantation. Auto-HSCT is not recommended and should be performed only in a clinical trial.

Myelodysplastic syndromes (MDS)

Allo-HSCT is considered the treatment of choice for adult patients with MDS or AML evolved from MDS and offers a good chance of long-term disease-free survival, if the treatment is performed before progression of the disease or if the patient is transplanted in CR after chemotherapy. The International Prognostic Score System (IPSS) is a valuable tool to assess a patient’s prognosis without HSCT. Additional prognostic factors, such as multilineage dysplasia and transfusion requirement, may be considered as well.85 The results seem to be better in allo-HSCT if the blast count does not exceed 5% at the time of transplant. The practice in Europe is to treat MDS patients with excess of marrow blasts with remission-induction therapy, but this approach has not been substantiated by prospective clinical trials. Treatment with azacytidine before HSCT is another option to reduce the risk for relapse, but has not yet been proven. The decision to proceed with allo-HSCT should be based on the risk of the disease and the risk of the transplant procedure as estimated by the EBMT risk score. The results of a large European study show that auto-HSCT can be recommended in patients with good-risk cytogenetic characteristics.86

Chronic lymphocytic leukaemia (CLL)

Allo-HSCT from an HLA-identical sibling or MUD is a treatment option for young patients having previously been treated with and progressing after fludarabine-containing regimens and have poor-risk disease as defined by clinical and cytogenetic/molecular assessments.87 Mature phase-II studies and registry analyses have shown that allo-HSCT is the only therapy with curative potential. In contrast to conventional treatment, it can provide long-term disease control even in genetically unfavourable and refractory cases, and is clearly superior to any other salvage chemotherapy.88 The promising new class of BTK, PI3K and BCL2 inhibitors may be considered as treatment alternative in patients who are at high risk of treatment-related mortality.


Diffuse large B-cell lymphoma (DLBCL)

Auto-HSCT remains the standard of care for patients with chemosensitive relapse of DLBCL in the rituximab era.89, 90, 91 With regard to the value of auto-HSCT as consolidation after rituximab-containing first-line therapy of DLBCL, a survival benefit for HSCT could not be shown in several randomized phase-III trials.91, 92 Therefore, upfront autologous HSCT cannot be considered as treatment standard in DLBCL. Auto-HSCT is less effective in patients with chemorefractory DLBCL but can result in long-term survival in a significant minority of them.93

Patients who relapse after auto-HSCT for DLBCL have only limited effective treatment perspectives. Although the available evidence is largely based on registry studies, it appears that allo-HSCT can provide long-term disease control in up to 40% of patients with DLBCL who have failed auto-HSCT, in particular if performed in chemosensitive disease.94, 95 Accordingly, allo-HSCT should be considered as a rescue option in eligible patients with this condition.91 This notion is supported by a phase-II prospective study.96 The value of allogeneic in comparison with auto-HSCT in high-risk relapse or refractory status of DLBCL needs to be defined by further studies.

Follicular lymphoma (FL)

Although in the rituximab era still not proven by a prospective randomized trial, auto-HSCT is considered as standard treatment option in patients who are in first or subsequent relapse of FL.91, 97 In contrast, prospective phase-III trials from the pre-rituximab as well as from the rituximab era have failed to show a survival benefit of consolidating auto-HSCT performed in first FL remission,98 implying that upfront auto-HSCT in FL should be performed only within the framework of a prospective clinical trial.91, 97 Results of auto-HSCT in truly refractory FL are poor. These patients should be offered alternative approaches. Long-term follow-up of retrospective studies of auto-HSCT for relapsed FL concordantly show that disease recurrence becomes increasingly infrequent after 6–8 years of follow-up, indicating that auto-HSCT could have curative potential in a subset of patients with FL.99 Disease control after auto-HSCT might be further improved by rituximab maintenance as shown in a randomized phase-III clinical trial.100

FL generally appears to be highly sensitive to graft-vs-lymphoma effects, translating into a pronounced efficacy of allo-HSCT in terms of relapse prevention in this disease.101, 102 However, owing to the good efficacy of first-line immunochemotherapy and in the absence of valid predictors of adverse outcome, there is no place for allo-HSCT in FL in first remission. Similarly, investigators tend to prefer immunochemotherapy with or without auto-HSCT for second-line treatment of FL. A prospective trial randomizing autologous vs allo-HSCT in this condition had to be closed prematurely because of slow accrual.103 Supported by evidence from several retrospective uncontrolled studies, allo-HSCT therefore is reserved as a potentially curative option for those patients who have failed auto-HSCT or multiple therapy lines, or who have become refractory.91, 97, 104

Waldenström’s macroglobulinaemia (lymphoplasmacytic lymphoma with IgM gammopathy) (WM)

Small retrospective studies and a large registry analysis suggested that auto-HSCT might improve the outcome of WM when applied as first-line consolidation.105, 106 With the event of more effective agents, such as rituximab, purine analogues and bortezomib, this approach is increasingly questionable and should not be followed outside of clinical trials. In contrast, auto-HSCT is an option for salvage therapy in selected patients with chemosensitive disease who have not been exposed to numerous treatment lines.106, 107 There is circumstantial evidence (effects of DLI and chronic GVHD, plateau in the relapse curves, efficacy in refractory disease) from registry studies that graft-vs-lymphoma is effective in WM.108, 109 Thus, allo-HSCT has been advocated as a treatment option for younger individuals with aggressive clinical course.110 Although a clear definition of high-risk WM is missing, indications for allo-HSCT might be considered along the criteria for poor-risk CLL (purine analogue refractoriness and relapsed disease with TP53 lesion).87

Mantle cell lymphoma (MCL)

Auto-HSCT consolidation is considered as standard part of first-line treatment of younger (<60–65 years) patients with MCL.93 This is based on several uncontrolled studies and one prospective randomized trial comparing auto-HSCT consolidation with IFN maintenance in patients with MCL in first remission.111 This trial demonstrated that auto-HSCT provides a significant PFS benefit, and—after longer follow-up—also an OS benefit over IFN.112 The results of upfront auto-HSCT in MCL can be further improved by incorporation of rituximab and high-dose ara-C into the induction regimen as observed in prospective randomized trials and cohort studies.113, 114 A registry analysis suggested that the benefit of auto-HSCT may also be relevant in fit elderly patients (65–70 years).115 The prognosis of patients with relapsed or refractory MCL relapse is generally poor. Although the results of salvage auto-HSCT are inferior to first-line transplants, auto-HSCT remains a rescue option for transplant-naïve patients.93, 116, 117

Although merely supported by retrospective studies, in the absence of reasonable alternative treatment options, allo-HSCT seems to be the only modality capable of providing long-term disease control in patients with relapsed and even refractory MCL.117, 118 Therefore, it is consensus to recommend allo-HSCT to patients with MCL who relapse or become refractory after auto-HSCT or an appropriately intensive pre-treatment.93 In contrast, there is no evidence to support upfront allo-HSCT in MCL outside of clinical trials. It remains to be shown whether novel molecular drugs, such as B cell receptor kinase inhibitors, will affect HSCT indications in MCL or other B cell malignancies in the future.119

T-cell lymphomas

Peripheral T-cell lymphomas usually carry a very poor prognosis. On the basis of results from phase II trials and registry analyses, auto-HSCT as consolidation of a first response represents a reasonable treatment option,120, 121, 122 whereas its role in the relapse setting is less clear. It might be best supported in chemosensitive ALCL-type peripheral T-cell lymphomas without prior autologous transplantation.123 The value of allo-HSCT as first-line consolidation in peripheral T-cell lymphoma is still under investigation. In contrast, phase II trials and registry analyses strongly support the notion that allo-HSCT is effective in relapsed and refractory peripheral T-cell lymphoma and the only curative modality in this condition.122, 123, 124, 125, 126

Mycosis fungoides (MF) and Sézary syndrome are the most common forms of primary cutaneous T-cell lymphomas.127 Although early stage MF has an excellent outcome, patients with EORTC/ISCL stages IIB to IV MF and Sézary syndrome have a dismal prognosis with conventional therapy, with median survivals of only 1–3 years from the time of diagnosis.128, 129, 130 Auto-HSCT can induce cutaneous T-cell lymphoma responses in these patients, but they are almost universally very short-lived, with median time to progression of 2–3 months, and therefore it is generally not recommended as a therapeutic strategy.131 Conversely, allo-HSCT offers patients with advanced-stage MF and Sézary syndrome a clinically relevant and persistent graft-vs-MF/Sézary syndrome effect, leading to OS rates of 54% at 3 years, 46% at 5 years and 44% at 7 years,132, 133 which despite the lack of well-designed comparative trials, would suggest this to be an advantageous and potentially curative option for these patients compared with their outcomes with only conventional therapy.

Hodgkin lymphoma (HL)

Auto-HSCT is the standard therapy for patients with HL in first chemosensitive relapse or refractory to first-line therapy but sensitive to salvage therapy as shown by two prospective clinical trials.134, 135 In contrast, there is no evidence supporting auto-HSCT in first CR. For truly primary refractory patients, for patients in chemo-refractory relapse, and for those who relapse after a previous auto-HSCT, a second one has a limited likelihood to induce durable remission, but it may be an option in patients ineligible for allo-HSCT.136, 137

Prospective phase II trials as well as retrospective cohort comparisons and registry analyses suggest that allo-HSCT can prolong survival in comparison with the limited non-transplant options in patients who fail autologous HSCT but respond to salvage therapy.136, 138, 139 Accordingly, allo-HSCT can be considered as the standard treatment option in eligible patients with sensitive relapse after auto-HSCT.140 The value of allo-HSCT is less established in refractory HL, but may be considered in the absence of effective treatment alternatives.141

Multiple myeloma (MM)

Auto-HSCT is clearly indicated for patients less than 70 years of age who respond to first-line treatment. Age should be considered in conjunction with the patient’s general health and fitness. New agents, such as the proteasome inhibitors (bortezomib) or the immunomodulatory drugs such as lenalidomide (IMiDs) may change the place of auto-HSCT. Ongoing studies are comparing induction with a combination of new agents, such as proteasome inhibitor with IMiDs, followed by upfront auto-HSCT vs delayed transplantation. Therefore, the role of first-line auto-HSCT may be challenged in the future. Best results are seen in patients achieving good responses prior to HSCT but some non-responding patients also benefit from this approach. High activity shown by IMiDs and bortezomib before transplantation has recently led to their use as consolidation and maintenance therapies after auto-HSCT. Maintenance therapy with lenalidomide post auto-HSCT may be considered. Two studies demonstrated an improvement in PFS142, 143 but an increase in OS in only one study.143 Double auto-HSCT has been shown to be superior to one auto-HSCT although the benefit of the second transplant appears to be restricted to patients not achieving CR or very good PR with the first transplant; consolidation and maintenance with agents such as thalidomide may be an alternative for these patients. However, the vast majority of patients still relapse. The use of a further transplant after re-induction therapy is an option and may be of particular benefit in patients achieving a long treatment-free interval after their first transplant(s) (at least 18–24 months).144 TBI should not be used in the conditioning regimen because of increased toxicity without appreciable benefit.

Allo-HSCT is a treatment with curative potential, but is associated with considerable NRM and might be used in selected high-risk patients. The results of the combination of auto-HSCT followed by RIC-allo are inconsistent. Two studies with long-term follow-up of patients treated upfront reported a superior outcome compared with single or double auto-HSCT.145, 146 and a third study shows a trend for better outcome.147 However, three other studies with shorter follow-up have so far not shown any benefit. Longer follow-up is needed. Some phase II studies of relapsed patients show encouraging results and one that retrospectively compared HSCT and RIC-allo based on the availability of a matched donor showed better PFS with RIC-allo, however, with no difference at 2 years in OS.148 The combination of auto-HSCT and unrelated RIC-allo is currently being investigated. Similarly to the autologous transplantation setting, new agents are complementary, non-redundant therapies and should be combined in the management of suitable allogeneic patients.

AL amyloidosis

Patients with systemic immunoglobulin-light-chain (AL) amyloidosis have been treated by auto-HSCT since 1994. A study with matched controls showed that amyloidosis patients without severe heart failure benefited from high dose therapy and auto-HSCT. This was not confirmed in a randomized trial including patients with advanced cardiac amyloidosis.149 Many recently published studies reported an improved early mortality and consistently good haematologic responses.

Allo-HSCT might be considered as a clinical option in younger patients who relapsed or did not respond after HSCT and received at least one new drug (lenalidomide or bortezomib).

Acquired severe aplastic anaemia (SAA)

First-line allogeneic HLA identical sibling HSCT is considered for young and adult patients with SAA who have a matched sibling donor.150, 151, 152 EBMT data show that outcomes of patients aged 30–40 years and 40–50 years are the same. However, a careful assessment of co-morbidities prior to HSCT should be made to determine fitness for up-front HSCT in the age group of 35–50 years, instead of first-line immunosuppressive therapy (IST) with ATG (preferably with horse ATG) and CYA; it is also advised to seek further advice from an AA specialist centre.

Patients transplanted from matched sibling donors and aged<30 years should receive conditioning with high dose CY (200 mg/kg), and for patients aged 30–50 years a fludarabine-based regimen with lower dose CY (120 mg/kg) used.153 All patients should also receive in vivo T-cell depletion with ATG, or alemtuzumab if available, because this will decrease the likelihood of developing chronic GVHD. There is no indication for using radiation in the conditioning for HLA identical sibling HSCT.

Allogeneic unrelated HSCT using a well-matched donor is indicated after failure to respond to one course of IST. A fludarabine-based regimen is recommended.154 Assessment of response to IST is usually made at 3–6 months. BM is the recommended stem cell source for HSCT in SAA from sibling or unrelated donor HSCT for ATG-based conditioning regimens.28, 153, 155, 156 Studies are ongoing to determine whether there is any preferred stem cell source for alemtuzumab-based conditioning.

Alternative donor HSCT, using either CB cells157, 158 or a haploidentical family donor159, 160 or a mismatch 9/10 donor, may be considered in the absence of a matched sibling or unrelated donor after failure to respond to IST. All patients should be screened for donor-directed HLA antibodies as their presence would preclude using that donor because of a predicted high risk of graft rejection. For cord blood transplant, a minimum of 4 × 107/kg total nucleated cells (frozen) is recommended. The current EBMT AAWP approved protocol for either CB or haploidentical HSCT should be followed.

Paroxysmal nocturnal haemoglobinuria (PNH)

The indications for HSCT in PNH have changed since the introduction of C5 blocking monoclonal Ab therapy with eculizumab. The current indications for HSCT depend on the individual clinical manifestations of PNH, and are (i) AA/PNH syndrome, that is, PNH occurring in the presence of severe BM failure with a hypocellular BM (using the same factors of age, disease severity, and for UD HSCT failure to respond to one course of IST) and (ii) clonal evolution of PNH to MDS/AML.152, 161, 162 Severe recurrent thrombosis is no longer a mandatory indication for HSCT, but can be taken into consideration when discussing the patient’s treatment strategy and it may also be an option in patients who have poor haematological response to eculizumab (that is, remaining severely transfusion-dependent regardless of anti-complement treatment). HSCT is not indicated for recurrent haemolytic crises, except for patients in countries that cannot afford eculizumab treatment. If needed, expert advice should be sought from a PNH specialist centre. The timing of HSCT and conditioning regimen in AA/PNH is the same as for acquired SAA outlined above.

Constitutional SAA

There is increasing awareness that constitutional SAA, including Fanconi anaemia and dyskeratosis congenita (DC) may not only present in childhood but also in adults, often with more subtle clinical features of the syndrome.

Allo-HSCT is the only treatment able to restore normal haemopoiesis in patients with Fanconi anaemia. Patients who have a suitably matched donor and who are transfusion-dependent should be transplanted at a young age, as outcomes are best before the age of 10 years. For matched siblings, excellent survival has been obtained with low dose CY alone (60 mg/kg).163 In a recent very large EBMT study, the optimal conditioning regimen was an irradiation-free, fludarabine-based conditioning regimen.164 Standard doses of chemotherapy and/or irradiation should be absolutely avoided in Fanconi anaemia HSCT, because of the underlying defect in DNA repair. BM stem cells should be used in preference to PBSC, as the latter is an independent risk factor for later second malignancy. In the absence of a matched sibling donor, a suitably matched UD should be considered, also using a fludarabine-based regimen, but the addition of low-dose irradiation may be indicated (and also for those patients with clonal evolution) because of a higher risk of graft rejection.

For DC, most of published data concerning HSCT relate to X-linked DC and indicate high mortality from liver and respiratory failure, as a consequence of the more recently recognized clinical features of DC, namely pulmonary fibrosis and cirrhosis. There are only anecdotal reports of HSCT for autosomal dominant DC because of TERC or TERT mutations in association with SAA. The state of organ damage (lung, gastrointestinal, liver) is an important factor for the eligibility of the patient for HSCT. For all types of SAA associated with DC, a RIC regimen incorporating fludarabine is currently recommended.165, 166 Discussion with a specialist in BMF is advised regarding possible HSCT.

Solid tumours


Supported by a strong rationale from laboratory studies and apparently ‘convincing’ results of early phase II studies, in the nineties, high-dose chemotherapy with auto-HSCT was uncritically adopted as a potentially curative option for solid tumours. For this reason, randomized trials comparing high-dose therapy with conventional control arm were difficult to conduct. As a result, the number and size of clinical studies initiated (and often abandoned before completion) to prove or disprove its value was largely insufficient. In fact, after a quarter of century of clinical research and thousands of patients receiving high-dose therapy, the benefit of a greater escalation of dose of chemotherapy with auto-HSCT in solid tumours, with the possible exception of selected patients with breast cancer (BC) and germ cell tumours, is still unsettled.

Breast cancer (BC)

The role of auto-HSCT for primary BC at high risk of recurrence (at least four involved axillary lymph nodes) has been assessed by several randomized trials,167 recently evaluated by a meta-analysis of individual patient data.168 Overall, it was shown that high-dose therapy prolonged disease-free survival when used as adjuvant therapy, and showed a benefit on BC-specific survival and OS in selected cohorts of patients.169, 170 Whether auto-HSCT has benefit in the context of contemporary taxane-based regimens and targeted therapies is largely unknown. Seven phase III studies have been published in peer-reviewed journals.167, 171 Most of these trials showed improved PFS in the high-dose therapy arm, but only one an OS advantage. Six randomized trials, including 866 metastatic BC patients, have been analysed in the parallel meta-analysis of individual patient data,168 showing a significant improvement in PFS but no improvement in OS.

Overall, based on the randomized studies so far, meta-analyses and retrospective studies,172 auto-HSCT may still represent a therapeutic option for well-informed younger patients harbouring HER2-negative tumours and having gross involvement of axillary nodes (adjuvant setting) or highly chemosensitive disease (advanced setting).

Germ cell tumours

High-dose therapy is not recommended as first-line therapy in this setting.173 In relapsed germ cell tumour, high-dose therapy is considered to be a therapeutic option,174, 175 especially when poor prognostic factors are present.176 A randomized study comparing conventional dose therapy with high-dose therapy is planned. Auto-HSCT is a standard of care for patients who are (primary) refractory to platinum-based chemotherapy or for those with a second or further relapse, excluding primary mediastinal disease.173 Multiple intensified cycles with carboplatin/etoposide is recommended as the standard high-dose treatment for germ cell tumour also owing to concerns that using a three-drug regimen would require dose reductions of the two most active drugs in this disease.

Other solid tumours

Data from randomized phase III studies comparing high-dose vs conventional-dose chemotherapy for first-line treatment of advanced ovarian cancer and limited or extensive small cell lung cancer177, 178 have shown no statistically significant difference in PFS or OS. Limitations due to study design, difficulty in recruitment and toxicity may have accounted for the lack of favourable results, that were expected based on previous phase II and retrospective analyses179 of such highly chemosensitive diseases.

In other chemosensitive histologies, including sarcomas and central nervous system tumours, data regarding autologous transplantation in adult patients are limited, again based on clinical trials without randomization and retrospective analyses.179 For this reason, high-dose therapy cannot be recommended as standard of care and should be considered within prospective studies when available. High-dose therapy can be regarded as a potential clinical option in selected patients with Ewing’s sarcoma 180, 181 and medulloblastoma.182

Allogeneic setting

There is no clinical experience of allografting in renal cell cancer that is TKI- and mTOR-refractory; nowadays, allo-HSCT should be considered, in renal cell cancer183 and other solid tumours.184, 185 only in the context of prospective studies. Attempts to improve the therapeutic index of allo-HSCT in solid tumours by innovative clinical strategies are underway.186

Cell therapy

Despite the great potential, cell therapy programs for cancer control still have a marginal role in the management of patients with solid tumours, although its use in the setting of melanoma and other malignancies187, 188, 189 seems ready for development as a routine therapy. This is due to limitations inherent to the technologies and products employed, and to the financial and structural burdens that are associated with cell therapy.190 This issue should be regarded as a priority for medical oncology and cell therapy/transplantation societies.

The story of SCT in solid tumours demonstrates the importance of adopting an internationally co-ordinated approach to the investigation of this treatment modality. There needs to be an increased emphasis on prospective trials that are statistically robust and have well-defined criteria for patient selection. Only these will be able to demonstrate whether HSCT, alone or incorporated into programs with novel therapeutic modalities, is worthwhile in patients for whom conventional treatments have often limited impact on survival.

Autoimmune diseases (AD)

Auto-HSCT should be considered for patients with severe AD progressing despite standard established and/or approved therapy. It has shown long-term prolonged survival with various degrees of evidence according to each AD-specific conditions. Patients should be referred to a centre with JACIE accreditation or equivalent, where appropriate inter-disciplinary interaction with combined haematological and AD specialists allow selection and management of AD patients. Local or central biobanking, within regulatory requirements, is essential to provide adequate serum, plasma and cell samples in addition to biological samples according to each AD category and organ involvement at baseline, during the immunosuppression-free remission, and at potential relapse.

Adult patients with the underlying AD should be considered as indications for auto-HSCT, when presenting: a) severe systemic sclerosis and disease duration (i) of less than 5 years since onset of first non-Raynaud’s symptoms and a modified Rodnan skin score 15 plus respiratory (with a diffusing capacity of the lung for carbon monoxide and/or forced vital capacity 80% of predicted and evidence of interstitial lung disease on high resolution computed tomography scan), cardiac (with conduction or rhythm disturbance, pericarditis) or renal involvement or (ii) of less than 2 years and no major organ dysfunction as defined above provided they had a modified Rodnan skin score of at least 20 and an acute phase response (level I);191 b) multiple sclerosis in the relapsing-remitting phase, showing high clinical and MRI inflammatory activity, with rapid deterioration despite the use of one or more lines of approved treatments; the ‘malignant’ (Marburg) forms and the secondary progressive disease, only when some inflammatory activity is still evident, with clinical relapses and/or new T2 MRI lesions on two subsequent scans, and with a sustained and increased in disability in the previous year and with an EDSS upper limit of 6.5, except for the malignant form (level II);192, 193 c) systemic lupus erythematosus early in the disease course, with sustained or relapsed activity defined by a BILAG A category, with either kidney (with a creatinine clearance >30 ml/min/m2 on renal biopsy of less than 12 months showing evidence of WHO class III or IV glomerulonephritis), neurologic, cardiovascular or pulmonary, vasculitis or autoimmune cytopenias after at least 6 months of the best standard therapy, using mycofenolate mofetil or CY with or without anti-CD20 (level II);53 d) Crohn’s disease, refractory to immunosuppressive agents and anti-TNF monoclonal antibodies, with sustained endoscopic or CT scan-proven activity or extensive disease in which surgical resection would expose the patient to the risk of small bowel syndrome or with refractory colonic disease and perianal lesions where coloprotectomy with a definitive stoma not accepted by the patient (level II); e) autoimmune cytopenias with either immune thrombocytopenia, autoimmune haemolytic anaemia and Evans’ syndrome refractory to at least two lines of treatment (including rituximab and TPO-receptor agonists for immune thrombocytopenia) (level II); f) for other AD, including rheumatoid arthritis, systemic vasculitis, dermatomyositis and polymyositis can be considered as exceptional indications. Chronic demyelinating inflammatory polyneuropathy and neuromyelitis optica, type 1 diabetes mellitus, refractory type II coeliac disease, autism spectrum disorders potentially respond, but experience of auto-HSCT has been relatively recent and patients should only be treated on approved prospective clinical trials.

Syngeneic as an alternative to auto-HSCT may be considered with comparable risks and potential greater benefit according to donor-related issues. Allo-HSCT outside of a clinical trial is highly discouraged in all ADs except for patients with immune thrombocytopenia, autoimmune haemolytic anaemia and Evans’ syndrome refractory to at least two lines of treatment (including rituximab and TPO-receptor agonists for immune thrombocytopenia) under the CO criterion.52

Both for adult and paediatric indications, specific recommendations include patient selection, stem cell collection, graft manipulation, conditioning regimens and supportive care. Comprehensive cardiopulmonary screening and pre-transplant evaluation are critically important to exclude patients at high risk of NRM.194

Priming chemotherapy is recommended to enhance mobilization whilst maintaining disease control and to prevent potential flare, which may be a consequence of G-CSF alone (level I). The recommended mobilization regimen is CY at 2–4 g/m2 with uromixetan and cautious hyper hydration followed by G-CSF 5–10 mcg/kg (level II). A minimum dose of 2 × 106/kg CD34+ cells should be reinfused, irrespective of any graft manipulation (level II). Among the many conditioning regimens reported, the ADWP recommends CY 200 mg/kg with polyclonal or monoclonal anti-T-cell serotherapy generally, with CY 120 mg/kg, fludarabine 150 mg/kg and anti-T-cell serotherapy as an alternative in paediatrics and BEAM+anti-T-cell serotherapy in multiple sclerosis specifically. After HSCT, all patients should remain under the direct routine combined care of the transplant and the AD specialists for at least the first 100 days post transplant, and then on a quarterly basis for the first 2 years even if clinically stable. Thereafter, joint annual review as a minimum is recommended. Long-term annual data reporting, including late effects, of all AD patients after HSCT to registries is a minimum recommendation.52

Status of transplants in specific diseases in children and adolescents

More than 20% of allo-HSCT are performed in patients below 20 years. However, at least one-third of HSCTs in children are performed for rare indications. Clinical trials to improve outcomes after HSCT in children have been limited by small numbers and disease-specific complications. Distinct side and late effects are exclusively related to the vulnerability of the developing organism, including child-specific organ dysfunction, delayed hormonal development, growth retardation, dental and skeletal damage, and the high risk of malignancies in congenital disorders with chromosomal breakage syndromes. During the last years, better HLA matching with non-sibling donors, the evolution of RIC regimen, better supportive care and better diagnosis of infectious complications, dramatically reduced NRM. That enabled offering allo-HSCT at an earlier disease course with better performance status and not as ‘last chance for cure’. However, the burden of acute and especially chronic GVHD is still a major limitation for patients who do not identify well-matched donors and have to be considered for outweighing the risk of this procedure. In such situations, nowadays HSCT from haploidentical family donors or from an unrelated CB might be performed within clinical studies in highly experienced and specialized centres.

Acute myeloid leukaemia (AML)

Childhood AML is a rare and heterogeneous disease, cure rates with intensive chemotherapy and extensive supportive care are around 60%. Better outcomes are reported for patients with favourable prognostic markers.195 Hence, HSCT is not recommended as a front-line therapy for good-risk patients with AML.196, 197 Allo-HSCT from an HLA-identical sibling in CR1 remains an option for children defined as high risk as it was proven to be more efficient than chemotherapy in some comparative studies, with EFS ranging from 55 to 72%.198, 199 Infant AML and children with FAB M0, M6 or M7 AML, who stand very poor chances of cure by chemotherapy or by auto-HSCT, are indications for HSCT in first remission.200 Results in children with AML undergoing haploidentical HSCT have shown some effect of NK alloreactivity suggesting that haploidentical HSCT may have a role in early phase very high-risk AML patients.201, 202

Auto-HSCT has been used as consolidation in children with AML, in CR1 after induction therapy and represented a possible alternative for high-risk children lacking a matched donor. Nevertheless, results of paediatric studies comparing auto-HSCT to chemotherapy were conflicting and are currently not recommended outside prospective trials addressing new questions.203 Children who experience AML relapse and who reach second remission are candidates for any kind of allo-HSCT. To improve remission quality, and to reduce post-transplant relapse, several studies are on the way, exploring new immunological mechanisms and pharmaceutical developments.

Acute lymphoid leukaemia (ALL)

The indications for HSCT in children with ALL in CR1 are limited to the subpopulation of high-risk ALL. Most study groups define these patients as having estimated EFS of less than 50%. The risk factors indicating the usefulness of HSCT are known molecular biological markers or chromosomal abnormalities, and biological factors including poor prednisone response, and resistance to initial chemotherapy including persistence of MRD.204 MRD became the most important prognostic factor for ALL relapse in children and should be used for better discrimination of high-risk and very high-risk groups.205, 206 For the latter patients, allo-HSCT from matched sibling donors or a well-matched unrelated donor and for the highest risk category also a mismatched donor is an option. Also, infants with very high-risk features benefit from allo-HSCT and are candidates for both related and well-matched unrelated HSCT.207 ALL patients, who experience an early or very early marrow relapse, still have a dismal prognosis when treated with conventional chemotherapy.208 Although nearly 90% achieve a second remission, most of them subsequently develop progressive disease. Both matched sibling donor HSCT and well-matched unrelated donor HSCT are clearly indicated in these patients since the outcomes are similar.209, 210 If a matched sibling or a well-matched unrelated donor cannot be identified, other types of donors such as CB, mismatched unrelated donors or haploidentical family donors can be indicated.19, 211 In contrast to adults, PBSC from HLA-compatible sibling donors show no advantage for engraftment, relapse incidence and OS compared with BM and therefore BM is the preferred stem cell source for children.212

Non-Hodgkin lymphoma

Nearly all children and adolescents are cured with multidrug chemotherapy. Only few patients are eligible for allo-HSCT: patients with residual disease after re-induction therapy of contemporary chemotherapy-protocols or patients with early NHL relapses and patients with inadequate response or relapse of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.213, 214, 215 All other approaches should be discussed with the experts of the front line chemotherapy trials.

Chronic myeloid leukaemia (CML)

Although allo-HSCT is the only curative option for patients with CML, the introduction of specific TKI has substantially modified the treatment strategies for all age groups. As children and adolescents have to be treated for an indefinite time with TKI, it has become clear that toxicities may make long-term TKI therapy less attractive compared with allo-HSCT.216, 217 HSCT has long-term complications of growth failure, infertility, chronic GVHD, metabolic syndrome and secondary malignancies, whereas prolonged TKI may cause growth failure, hepatic and cardiac complications.216, 217, 218 Nowadays, it is accepted that all children and adolescents with CML-CP should initially be treated with imatinib and maintained with TKI therapy indefinitely if there is a good response.219, 220 No long-term results are evaluable to show whether children will stay in sustained complete molecular remission after TKI discontinuation. Further, it is considered that allo-HSCT with an HLA-identical sibling donor or closely matched unrelated donor is a clinical option for patients with treatment failure or recurrence after receiving salvage second-generation TKI treatment.221 Further, it is considered that allo-HSCT with an HLA-identical sibling donor or closely matched unrelated donor can be considered for patients with treatment failure or recurrence after receiving salvage second-generation TKI treatment. However, prospective cooperative studies are needed to address this complex issue in young patients with CML.220, 222

MDS, juvenile myelomonocytic leukaemia

Allo-HSCT from a sibling donor or a well-matched unrelated donor is the treatment of choice for children with primary MDS including juvenile myelomonocytic leukaemia, as well as secondary AML.223, 224, 225 The role of auto-HSCT in children with MDS remains controversial and is generally not recommended.

Inherited diseases

Primary immunodeficiencies

Primary immunodeficiencies are genetic disorders characterized by defective or impaired innate or adaptive immunity. Of these, severe combined immunodeficiencies are the most severe, leading to death in infancy or early childhood unless treated appropriately. Many other immunodeficiencies lead to decreased quality of life with premature death through childhood or early adulthood. Recurrent, persistent or opportunistic infections are the classic hallmarks of primary immunodeficiencies, although immunodysregulation or malignancies are increasingly recognized presentations. Allo-HSCT can cure most cellular immunodeficiencies affecting innate or adaptive immunity. Advances in a number of areas including earlier diagnosis, more accurate HLA-typing, an increasing range of stem cell sources, less toxic conditioning regimens and improved supportive care have enabled increasing successful outcomes, of over 90% survival in some conditions. Owing to the clinical heterogeneity of the patients, the several existing variants for each primary immunodeficiency associated with the need to carefully evaluate the patient’s clinical conditions, and the fact that drugs are used in different dosages, combinations and time schedules according to the disease, the age and the clinical condition of the patient.

HSCT for primary immunodeficiency should be performed in a centre regularly performing such transplants and actively participating within EBMT’s inborn errors working party. The guidelines for each particular inherited condition are published on the EBMT’s website and reviewed regularly by the Inborn Errors working party members.226 Allo-HSCT is indicated for severe primary immunodeficiencies from both HLA-identical and alternative donors, including umbilical CB.

Severe combined immunodeficiency

The diagnosis of SCID is a paediatric emergency, and these patients should undergo HSCT as soon as possible. An allo-HSCT results in a survival rate of more than 90% when carried out shortly after birth.227 Factors that influence prognosis include the age, the type of SCID (B lymphocyte+ vs B lymphocyte−), and the clinical state at the time of diagnosis, in particular the presence of viral respiratory infection, and the degree of HLA histocompatibility. In the presence of an HLA-identical family donor (20–30% of SCID patients), HSCT can be performed in certain SCID forms (particularly those with an absence of NK cells) without any conditioning regimen, and its course is characterized by the remarkable rarity of acute and chronic GVHD without any prophylaxis, and by the rapid development of T lymphocyte function after transplant. The restoration of B lymphocyte function nearly always occurs in patients with the B lymphocyte +ve form of SCID, but is absent in 40% of those with a B lymphocyte −ve form. In the absence of an HLA-identical family donor, HSCT from a partially HLA-compatible donor is recommended. In this respect, the use of a conditioning regimen has a positive effect on survival in the B lymphocyte—SCID group but not in other SCID groups. HSCT from unrelated HLA-compatible donors and unrelated umbilical CB and haploidentical HSCT from related donors (that is, one of the two parents) are alternative options, with improving outcomes.228

Other primary immunodeficiencies

Allo-HSCT can cure most of the T lymphocyte immunodeficiencies, Wiskott-Aldrich syndrome, phagocyte disorders such as leukocyte adhesion deficiency and chronic granulomatous diseases, haemophagocytic syndromes such as familial lymphohistiocytosis, and a growing number of other immunodeficiencies. These patients require conditioning. As for patients with SCID, prognostic factors include age at transplant, the type of primary immunodeficiency, and the clinical state at the time of diagnosis, in particular, the presence of viral respiratory infection, and the degree of HLA histocompatibility. Survival is similar using an HLA-identical family donor or HLA-matched unrelated donor.228 Patients transplanted at an early age have a better outcome than those transplanted when older.

Inherited diseases: metabolic diseases

Most of the metabolic diseases considered for HSCT are lysosomal storage diseases that rely on transfer of enzyme from donor-derived blood cells to the reticuloendothelial system and solid organs. The successful outcome of HSCT can be affected by the lack of engraftment (secondary rejection is comparatively common), the enzyme levels of the donor (lower if they are a sibling carrier of the disease), and the degree of sustained donor chimerism and possibly by the immune processes directed against the normal donor enzyme. CB transplantation is particularly successful in patients with Hurler's Syndrome.229 In diseases with the central nervous system involvement, amelioration is dependent on the replacement of recipient microglial cells by cells of donor origin. This process is slow and the time taken to process abnormal storage material produces a delay between transplant and disease stabilization. This can last up to 15 months, making it necessary to predict the quality of life 18 months beyond the first consideration of HSCT (allowing for a donor search, clinical assessment and conditioning).

Aplastic anaemia, pure red cell aplasia (Blackfan-Diamond) and Fanconi anaemia

An allo-HSCT with an HLA-identical family donor is the treatment of choice for children with acquired SAA. A course of intensive immunosuppressive therapy (ATG and CYA) is one option for patients who lack an HLA-compatible family donor. The search for an unrelated donor should be initiated before they receive the immunosuppressive therapy. An alternative option for children who lack an HLA-compatible family donor is upfront matched unrelated donor HSCT if a donor is readily available, as results of MUD HSCT in children are now similar to matched sibling HSCT.230, 231, 232, 233, 234 For children who fail their first course of immunosuppression, if a well-matched unrelated donor is identified, the transplant or a second course of immunosuppression should be given, according to clinical status. Children with Blackfan-Diamond anaemia having a matched sibling should be transplanted if they do not respond to steroids.235 Children with FA should be transplanted if they have a HLA-identical sibling donor or a well-matched unrelated donor. For patients who lack a well-matched donor, HSCT should be considered with a mismatched unrelated donor or with CB stem cells in the context of a clinical protocol.


The outcome of HSCT for thalassaemia has progressively improved with the identification of the Pesaro Classes of Risk and the development of new conditioning regimens and supportive therapies. Allo-HSCT from a healthy related sibling donor or a related CB represents the treatment of choice for young patients with homozygous thalassaemia. For patients who lack a sibling donor, a transplant from a well-matched unrelated donor is a possibility.29 Extended haplotype matching seems to impact positively on prognosis after unrelated donor HSCT.236, 237, 238, 239, 240 Developments of conventional therapy have improved both the quality and the duration of life for patients with sickle cell disease; however, today a prediction on the severity and onset of complications is not possible. For this reason, HSCT from an HLA-identical sibling or—for a small subset of patients—from a well-matched non-sibling donor should be offered.241, 242, 243, 244

Solid tumours

Neuroblastoma (stage 4 beyond the age of 1 year, or high-risk factors in lower stages) is still the only indication where the benefit of auto-HSCT has been demonstrated by randomized trials.245, 246 Although to date the published results do not demonstrate an unequivocal benefit for consolidation with HDT, children and adolescents with solid tumours might undergo auto-HSCT following high-dose chemotherapy within clinical research trials, preferably as part of first-line treatment strategies in the following situations: neuroblastoma (high risk, >CR1), Ewing’s Sarcoma (high risk or>CR1), Brain tumours: children with medulloblastoma and high-grade gliomas responsive to chemotherapy in an attempt to avoid or postpone radiotherapy, soft tissue sarcoma: stage IV or in responding relapse, germ cell tumours: after a relapse or with progressive disease and Wilm's tumour: relapse.

Generally, allo-HSCT in children with solid tumours should only be explored within prospective trials in highly experienced centres.

Autoimmune diseases

For paediatric patients, auto-HSCT is a CO for carefully selected subpopulations of patients with juvenile inflammatory arthritis with polyarticular course or polyarticular onset, no response to equivalent prednisone dose of 2 mg/kg/day (max 60 mg daily) for eight consecutive weeks, and inadequate response to, or intolerance to, at least two disease modifying antirheumatic drugs, including biological agents or unacceptable toxicity from disease modifying antirheumatic drugs or corticosteroid therapy (level II), for SSc, systemic lupus erythematosus, Crohn’s disease which requires special consideration and appropriate expertise in patient selection (level III), autoimmune cytopenia where no fully HLA compatible sibling or unrelated donor can be identified, or in patients with Evans’ syndrome with no 9/10 HLA matched unrelated donor (level II).


  1. 1

    Schmitz N, Gratwohl A, Goldman JM . Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders. Current practice in Europe in 1996 and proposals for an operational classification. Accreditation Sub-Committee of the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1996; 17: 471–477.

    CAS  PubMed  Google Scholar 

  2. 2

    Goldman JM, Schmitz N, Niethammer D, Gratwohl A . Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe in 1998. Accreditation Sub-Committee of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1998; 21: 1–7.

    CAS  PubMed  Google Scholar 

  3. 3

    Urbano-Ispizua A, Schmitz N, de Witte T, Frassoni F, Rosti G, Schrezenmeier H et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe. Bone Marrow Transplant 2002; 29: 639–646.

    CAS  PubMed  Google Scholar 

  4. 4

    Ljungman P, Urbano-Ispizua A, Cavazzana-Calvo M, Demirer T, Dini G, Einsele H et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe. Bone Marrow Transplant 2006; 37: 439–449.

    CAS  Google Scholar 

  5. 5

    Ljungman P, Bregni M, Brune M, Cornelissen J, de Witte T, Dini G et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant 2010; 45: 219–234.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007; 110: 4576–4583.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Ferrara GB, Bacigalupo A, Lamparelli T, Lanino E, Delfino L, Morabito A et al. Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain. Blood 2001; 98: 3150–3155.

    CAS  PubMed  Google Scholar 

  8. 8

    Bacigalupo A . A closer look at permissive HLA mismatch. Blood 2013; 122: 3555–3556.

    CAS  PubMed  Google Scholar 

  9. 9

    Pidala J, Wang T, Haagenson M, Spellman SR, Askar M, Battiwalla M et al. Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality. Blood 2013; 122: 3651–3658.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Fleischhauer K, Locatelli F, Zecca M, Orofino MG, Giardini C, De Stefano P et al. Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction. Blood 2006; 107: 2984–2992.

    CAS  Google Scholar 

  11. 11

    Beatty PG, Clift RA, Mickelson EM, Nisperos BB, Flournoy N, Martin PJ et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313: 765–771.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Trigg ME, Gingrich R, Goeken N, de Alarcon P, Klugman M, Padley D et al. Low rejection rate when using unrelated or haploidentical donors for children with leukemia undergoing marrow transplantation. Bone Marrow Transplant 1989; 4: 431–437.

    CAS  PubMed  Google Scholar 

  13. 13

    Bozdech MJ, Sondel PM, Trigg ME, Longo W, Kohler PC, Flynn B et al. Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection. Exp Hematol 1985; 13: 1201–1210.

    CAS  PubMed  Google Scholar 

  14. 14

    Henslee-Downey PJ, Parrish RS, Macdonald JS, Romond EH, Marciniak E, Coffey C et al. Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant. Transplantation 1996; 61: 738–745.

    CAS  PubMed  Google Scholar 

  15. 15

    Aversa F, Tabilio A, Velardi A, Terenzi A, Falzetti F, Carotti A et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23: 3447–3454.

    PubMed  PubMed Central  Google Scholar 

  17. 17

    Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood 2008; 112: 3574–3581.

    CAS  Google Scholar 

  18. 18

    Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A et al. Megadose transplantation of purified peripheral blood CD34+ progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 2001; 27: 777–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R et al. Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size. An analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group. Blood 2010; 115: 3437–3446.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Burroughs LM, O'Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ et al. Comparison of outcomes of HLA matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008; 14: 1279–1287.

    PubMed  PubMed Central  Google Scholar 

  22. 22

    Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant 2013; 19: 117–122.

    CAS  Google Scholar 

  23. 23

    Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C et al. Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transplant. 2008; 14: 748–758.

    PubMed  PubMed Central  Google Scholar 

  24. 24

    DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol 2009; 27: 4767–4773.

    CAS  Article  Google Scholar 

  25. 25

    DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009; 113: 5720–5726.

    CAS  Google Scholar 

  26. 26

    Duarte RF, Shaw BE, Marín P, Kottaridis P, Ortiz M, Morante C et al. Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. Bone Marrow Transplant 2011; 46: 52–58.

    CAS  PubMed  Google Scholar 

  27. 27

    Schmitz N, Eapen M, Horowitz MM, Zhang MJ, Klein JP, Rizzo JD et al. Long-term outcome of patients given transplants of mobilized blood or bone marrow: A report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. Blood 2006; 108: 4288–4290.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E et al. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 2007; 110: 1397–1400.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica 2014; 99: 811–820.

    PubMed  PubMed Central  Google Scholar 

  30. 30

    Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    PubMed  PubMed Central  Google Scholar 

  32. 32

    Rodrigues CA, Rocha V, Dreger P, Brunstein C, Sengeloev H, Finke J et al. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood. Haematologica 2014; 99: 370–377.

    PubMed  PubMed Central  Google Scholar 

  33. 33

    Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105: 1343–1347.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    MacMillan ML, Weisdorf DJ, Brunstein CG, Cao Q, DeFor TE, Verneris MR et al. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood 2009; 113: 2410–2415.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Rodrigues CA, Sanz G, Brunstein CG, Sanz J, Wagner JE, Renaud M et al. Analysis of risk factors for outcomes after unrelated cord blood transplantation in adults with lymphoid malignancies: a study by the Eurocord-Netcord and Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2009; 27: 256–263.

    PubMed  PubMed Central  Google Scholar 

  36. 36

    Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116: 4693–4699.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Rocha V, Rio B, Garnier F et al. Reduced intensity conditioning regimen in single unrelated cord blood transplantation in adults with hematological malignant disorders. A Eurocord-Netcord and SFGM-TC Survey [abstract] Blood (ASH Annual Meeting Abstracts) 2006; 108: 3143.

    Google Scholar 

  38. 38

    Miyakoshi S, Kami M, Tanimoto T, Yamaguchi T, Narimatsu H, Kusumi E et al. Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases. Transplantation 2007; 84: 316–322.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Cutler C, Stevenson K, Kim HT, Brown J, McDonough S, Herrera M et al. Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis. Bone Marrow Transplant 2011; 46: 659–667.

    CAS  Google Scholar 

  40. 40

    Brunstein CG, Eapen M, Ahn KW, Appelbaum FR, Ballen KK, Champlin RE et al. Reduced intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes. Blood 2012; 119: 5591–5598.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Fernández MN, Regidor C, Cabrera R, García-Marco JA, Forés R, Sanjuán I et al. Unrelated umbilical cord blood transplants in adults: Early recovery of neutrophils by supportive co-transplantation of a low number of highly purified peripheral blood CD34+ cells from an HLA-haploidentical donor. Exp Hematol 2003; 31: 535–544.

    PubMed  PubMed Central  Google Scholar 

  42. 42

    Sánchez-Ortega I, Arnan M, Patiño B, Herrero MJ, Querol S, Duarte RF . Early engraftment and full-donor chimerism after single-cord blood plus third-party donor dual transplantation in patients with high-risk acute leukemia. Bone Marrow Transplant 2014; 49: 145–147.

    PubMed  Google Scholar 

  43. 43

    Kwon M, Bautista G, Balsalobre P, Sánchez-Ortega I, Serrano D, Anguita J et al. Haplo-cord transplantation using CD34 cells from a third-party donor to speed engraftment in high-risk patients with hematologic disorders. Biol Blood Marrow Transplant 2014; 20: 2015–2022.

    CAS  PubMed  Google Scholar 

  44. 44

    Martino R, Iacobelli S, Brand R, Jansen T, van Biezen A, Finke J et al. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood 2006; 108: 836–846.

    CAS  Article  Google Scholar 

  45. 45

    Sureda A, Robinson S, Canals C, Carella AM, Boogaerts MA, Caballero D et al. Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2008; 26: 455–462.

    CAS  Google Scholar 

  46. 46

    Martino R, de Wreede L, Fiocco M, van Biezen A, von dem Borne PA, Hamladji RM et al. Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with &lt;10% BM blasts: a report from EBMT. Bone Marrow Transplant 2013; 48: 761–770.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Bitan M, He W, Zhang MJ, Abdel-Azim H, Ayas MF, Bielorai B et al. Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens. Blood 2014; 123: 1615–1620.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Claviez A, Canals C, Dierickx D, Stein J, Badell I, Pession A et al. Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation. Blood 2009; 114: 2060–2067.

    CAS  PubMed  Google Scholar 

  49. 49

    Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol 2012; 13: 1035–1044.

    PubMed  Google Scholar 

  50. 50

    Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 1998; 352: 1087–1092.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica 2010; 95: 284–292.

    PubMed  PubMed Central  Google Scholar 

  52. 52

    Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Cervera R et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2012; 47: 770–790.

    CAS  Google Scholar 

  53. 53

    Illei GG, Cervera R, Burt RK, Doria A, Hiepe F, Jayne D et al. Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus. Ann Rheum Dis 2011; 70: 2071–2074.

    PubMed  PubMed Central  Google Scholar 

  54. 54

    Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    CAS  Article  Google Scholar 

  55. 55

    Sorror M, Storer B, Sandmaier BM, Maloney DG, Chauncey TR, Langston A et al. Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 2008; 112: 1992–2001.

    PubMed  PubMed Central  Google Scholar 

  56. 56

    Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 2007; 25: 4246–4254.

    Google Scholar 

  57. 57

    Sorror ML, Storer BE, Maloney DG, Sandmaier BM, Martin PJ, Storb R . Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood 2008; 111: 446–452.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Saad A, Mahindra A, Zhang MJ, Zhong X, Costa LJ, Dispenzieri A et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 2014; 20: 402–408.

    PubMed  Google Scholar 

  59. 59

    Sorror ML, Storb RF, Sandmaier BM, Maziarz RT, Pulsipher MA, Maris MB et al. Comorbidity-Age Index: A clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol 2014; 32: 3249–3256.

    PubMed  PubMed Central  Google Scholar 

  60. 60

    Gratwohl A, Brand R, Niederwieser D, Baldomero H, Chabannon C, Cornelissen J et al. Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation. J Clin Oncol 2011; 29: 1980–1986.

    PubMed  PubMed Central  Google Scholar 

  61. 61

    Gratwohl A, Brand R, McGrath E, van Biezen A, Sureda A, Ljungman P et al. Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation. Haematologica 2014; 99: 908–915.

    PubMed  PubMed Central  Google Scholar 

  62. 62

    Gorin NC, Labopin M, Frassoni F, Milpied N, Attal M, Blaise D et al. Identical outcome after autologous or allogeneic genoidentical hematopoietic stem-cell transplantation in first remission of acute myelocytic leukemia carrying inversion 16 or t(8;21): a retrospective study from the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol 2008; 26: 3183–3188.

    PubMed  Google Scholar 

  63. 63

    Schlenk RF, Taskesen E, van Norden Y, Krauter J, Ganser A, Bullinger L et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood 2013; 122: 1576–1582.

    CAS  PubMed  Google Scholar 

  64. 64

    Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100: 4325–4336.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Nagler A, Labopin M, Gorin NC, Ferrara F, Sanz MA, Wu D et al. Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Haematologica 2014; 99: 1380–1386.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Terwijn M, van Putten WL, Kelder A, van der Velden VH, Brooimans RA, Pabst T et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42 A study. J Clin Oncol 2013; 31: 3889–3897.

    PubMed  PubMed Central  Google Scholar 

  67. 67

    Messina C, Candoni A, Carrabba MG, Tresoldi C, Sala E, Tassara M et al. Wilms tumor gene 1 transcript levels in leukapheresis of peripheral blood haematopoietic cells predict relapse risk in patients autografted for acute myeloid leukemia. Biol Blood Marrow Transplant 2014; 20: 1586–1591.

    CAS  PubMed  Google Scholar 

  68. 68

    Hourigan CS, McCarthy P, de Lima M . Back to the future! The evolving role of maintenance therapy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2014; 20: 154–163.

    Google Scholar 

  69. 69

    Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood 2011; 118: 6037–6042.

    CAS  Google Scholar 

  70. 70

    Pastore F, Dufour A, Benthaus T, Metzeler KH, Maharry KS, Schneider S et al. Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia. J Clin Oncol 2014; 32: 1586–1594.

    PubMed  PubMed Central  Google Scholar 

  71. 71

    Sun CL, Francisco L, Kawashima T, Leisenring W, Robison LL, Baker KS et al, Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood 2010; 116: 3129–3139.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Keating A, DaSilva G, Perez WS, Gupta V, Cutler CS, Ballen KK et al. Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research. Haematologica 2013; 98: 185–192.

    PubMed  PubMed Central  Google Scholar 

  73. 73

    Holter Chakrabarty JL, Rubinger M, Le-Rademacher J, Wang HL, Grigg A, Selby GB et al. Autologous is superior to allogeneic hematopoietic cell transplantation for acute promyelocytic leukemia in second complete remission. Biol Blood Marrow Transplant 2014; 20: 1021–1025.

    PubMed  Google Scholar 

  74. 74

    Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K et al. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood 2013; 121: 3095–3102.

    CAS  PubMed  Google Scholar 

  75. 75

    Watts JM, Tallman MS . Acute promyelocytic leukemia: What is the new standard of care? Blood Rev 2014; 28: 205–212.

    PubMed  Google Scholar 

  76. 76

    Wetzler M, Watson D, Stock W, Koval G, Mulkey FA, Hoke EE et al. Autologous transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation: results of CALGB Study 10001 (Alliance). Haematologica 2014; 99: 111–115.

    PubMed  PubMed Central  Google Scholar 

  77. 77

    Cornelissen JJ, van der Holt B, Verhoef GE, van't Veer MB, van Oers MH, Schouten HC et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 2009; 113: 1375–1382.

    CAS  PubMed  Google Scholar 

  78. 78

    Gorin NC, Labopin M, Polge E, Cordonnier C, Jouet JP, Michallet M et al. Risk assessment in adult acute lymphoblastic leukaemia before early haemopoietic stem cell transplantation with a geno-identical donor: an easy clinical prognostic score to identify patients who benefit most from allogeneic haemopoietic stem cell transplantation. Leukemia 2003; 17: 1596–1599.

    PubMed  Google Scholar 

  79. 79

    Gupta V, Richards S, Rowe J . Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood 2013; 121: 339–350.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Giebel S, Labopin M, Gorin NC, Caillot D, Leguay T, Schaap N et al. Improving results of autologous stem cell transplantation for Philadelphia-positive acute lymphoblastic leukaemia in the era of tyrosine kinase inhibitors: a report from the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Eur J Cancer 2014; 50: 411–417.

    PubMed  Google Scholar 

  81. 81

    Powles R, Sirohi B, Treleaven J, Kulkarni S, Tait D, Singhal S et al. The role of posttransplantation maintenance chemotherapy in improving the outcome of autotransplantation in adult acute lymphoblastic leukemia. Blood 2002; 100: 1641–1647.

    CAS  Google Scholar 

  82. 82

    Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 2007; 109: 58–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Alchalby H, Zabelina T, Stübig T, van Biezen A, Bornhäuser M, Di Bartolomeo P et al. Allogeneic stem cell transplantation for myelofibrosis with leukemic transformation. A Study of the MPN-Subcommittee of the CMWP of the EBMT. Biol Blood Marrow Transplant 2014; 20: 279–281.

    Google Scholar 

  84. 84

    Kröger N, Holler E, Kobbe G, Bornhäuser M, Schwerdtfeger R, Baurmann H et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 2009; 114: 5264–5270.

    PubMed  Google Scholar 

  85. 85

    Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23: 7594–7603.

    PubMed  Google Scholar 

  86. 86

    Oosterveld M, Suciu S, Verhoef G, Labar B, Belhabri A, Aul C et al. The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921). Leukemia 2003; 17: 859–868.

    CAS  PubMed  Google Scholar 

  87. 87

    Dreger P, Corradini P, Kimby E, Michallet M, Milligan D, Schetelig J et al. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia 2007; 21: 12–17.

    CAS  PubMed  Google Scholar 

  88. 88

    Herth I, Dietrich S, Benner A, Hegenbart U, Rieger M, Stadtherr P et al. The impact of allogeneic stem cell transplantation on the natural course of poor-risk chronic lymphocytic leukemia as defined by the EBMT consensus criteria: a retrospective donor versus no donor comparison. Ann Oncol 2014; 25: 200–206.

    CAS  PubMed  Google Scholar 

  89. 89

    Gisselbrecht C, Schmitz N, Mounier N, Singh GD, Linch DC, Trneny M et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol 2012; 30: 4462–4469.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90

    Mounier N, Canals C, Gisselbrecht C, Cornelissen J, Foa R, Conde E et al. High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 2012; 18: 788–793.

    PubMed  Google Scholar 

  91. 91

    Ghielmini M, Vitolo U, Kimby E, Montoto S, Walewski J, Pfreundschuh M et al. ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol 2013; 24: 561–576.

    CAS  PubMed  Google Scholar 

  92. 92

    Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol 2012; 13: 1250–1259.

    CAS  PubMed  Google Scholar 

  93. 93

    Robinson S, Dreger P, Caballero D, Corradini P, Geisler C, Ghielmini M et al. The EBMT/EMCL consensus project on the role of autologous and allogeneic stem cell transplantation in mantle cell lymphoma. Leukemia 2014; 29: 464–473.

    PubMed  Google Scholar 

  94. 94

    van Kampen RJ, Canals C, Schouten HC, Nagler A, Thomson KJ, Vernant JP et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin's lymphoma relapsing after an autologous stem-cell transplantation: An Analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol 2011; 29: 1342–1348.

    Google Scholar 

  95. 95

    Rigacci L, Puccini B, Dodero A, Iacopino P, Castagna L, Bramanti S et al. Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: A GITMO study. Ann Hematol 2012; 91: 931–940.

    PubMed  PubMed Central  Google Scholar 

  96. 96

    Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M et al. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol 2014; 15: 757–766.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97

    Montoto S, Corradini P, Dreyling M, Ghielmini M, Kimby E, Lopez-Guillermo A et al. Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party. Haematologica 2013; 98: 1014–1021.

    PubMed  PubMed Central  Google Scholar 

  98. 98

    Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A et al. Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood 2008; 111: 4004–4013.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99

    Rohatiner AZ, Nadler L, Davies AJ, Apostolidis J, Neuberg D, Matthews J et al. Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. J Clin Oncol 2007; 25: 2554–2559.

    PubMed  PubMed Central  Google Scholar 

  100. 100

    Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B et al. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: A Prospective Randomized Trial From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2013; 31: 1624–1630.

    CAS  PubMed  Google Scholar 

  101. 101

    van Besien K, Carreras J, Bierman PJ, Logan BR, Molina A, King R et al. Unrelated donor hematopoietic cell transplantation for non-hodgkin lymphoma: long-term outcomes. Biol Blood Marrow Transplant 2009; 15: 554–563.

    PubMed  PubMed Central  Google Scholar 

  102. 102

    Robinson SP, Canals C, Luang JJ, Tilly H, Crawley C, Cahn JY et al. The outcome of reduced intensity allogeneic stem cell transplantation and autologous stem cell transplantation when performed as a first transplant strategy in relapsed follicular lymphoma: an analysis from the Lymphoma Working Party of the EBMT. Bone Marrow Transplant 2013; 48: 1409–1414.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Tomblyn MR, Ewell M, Bredeson C, Kahl BS, Goodman SA, Horowitz MM et al. Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first complete response or first partial response. Biol Blood Marrow Transplant 2011; 17: 1051–1057.

    Google Scholar 

  104. 104

    Thomson KJ, Morris EC, Milligan D, Parker AN, Hunter AE, Cook G et al. T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma. J Clin Oncol 2010; 28: 3695–3700.

    Google Scholar 

  105. 105

    Dreger P, Schmitz N . Autologous stem cell transplantation as part of first-line treatment of Waldenstrom's Macroglobulinemia. Biol Blood Marrow Transplant 2007; 13: 623–624.

    PubMed  Google Scholar 

  106. 106

    Kyriakou C, Canals C, Sibon D, Cahn JY, Kazmi M, Arcese W et al. High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2010; 28: 2227–2232.

    CAS  PubMed  Google Scholar 

  107. 107

    Dimopoulos M, Kastrdis E, Owen RG, Kyle RA, Landgren O, Morra E et al. Treatment recommendations for patients with Waldenstrom macroglobyulinemia (WM) and related disorders: IWWM-7 consensus. Blood 2014; 124: 1404–1411.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. 108

    Kyriakou C, Canals C, Cornelissen JJ, Socie G, Willemze R, Ifrah N et al. Allogeneic stem-cell transplantation in patients with waldenstrom macroglobulinemia: report from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol 2010; 28: 4926–4934.

    PubMed  Google Scholar 

  109. 109

    Garnier A, Robin M, Larosa F, Golmard JL, Le GS, Coiteux V et al. Allogeneic hematopoietic stem cell transplantation allows long-term complete remission and curability in high-risk Waldenstrom's macroglobulinemia. Results of a retrospective analysis of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Haematologica 2010; 95: 950–955.

    PubMed  PubMed Central  Google Scholar 

  110. 110

    Buske C, Leblond V . How to manage Waldenstrom's macroglobulinemia. Leukemia 2013; 27: 762–772.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood 2005; 105: 2677–2684.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. 112

    Hoster E, Metzner B, Forstpointner R, Pfreundschuh M, Trumper L, Hallek M et al. Autologous stem cell transplantation and addition of rituximab independently prolong response duration in advanced stage mantle cell lymphoma. Blood (ASH Annual Meeting Abstracts) 2009; 114: 880.

    Google Scholar 

  113. 113

    Hermine O, Hoster E, Walewski J, Ribrag V, Brousse N, Thieblemont C et al. Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation (ASCT) increases overall survival when compared to 6 courses of CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: Final Analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net). Blood (ASH Annual Meeting Abstracts) 2012; 120: 151.

    Google Scholar 

  114. 114

    Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M et al. Long-term progression-free survival of mantle cell lymphoma following intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: A non-randomized phase-II multicenter study by the Nordic Lymphoma Group. Blood 2008; 112: 2687–2693.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Jantunen E, Canals C, Attal M, Thomson K, Milpied N, Buzyn A et al. Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol 2012; 23: 166–171.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116

    Tam CS, Bassett R, Ledesma C, Korbling M, Alousi A, Hosing C et al. Mature results of the MD Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood 2009; 113: 4144–4452.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117

    Fenske TS, Zhang MJ, Carreras J, Ayala E, Burns LJ, Cashen A et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality. J Clin Oncol 2014; 32: 273–281.

    PubMed  Google Scholar 

  118. 118

    Dietrich S, Tielesch B, Rieger M, Nickelsen M, Pott C, Witzens-Harig M et al. Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma. Cancer 2011; 117: 1901–1910.

    PubMed  Google Scholar 

  119. 119

    Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013; 369: 507–516.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Reimer P, Rudiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 2009; 27: 106–113.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. 121

    d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012; 30: 3093–3099.

    CAS  PubMed  Google Scholar 

  122. 122

    Dreyling M, Thieblemont C, Gallamini A, Arcaini L, Campo E, Hermine O et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol 2013; 24: 857–877.

    CAS  PubMed  Google Scholar 

  123. 123

    Smith SM, Burns LJ, van BK, Lerademacher J, He W, Fenske TS et al. Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. J Clin Oncol 2013; 31: 3100–3109.

    PubMed  PubMed Central  Google Scholar 

  124. 124

    Kyriakou C, Canals C, Finke J, Kobbe G, Harousseau JL, Kolb HJ et al. Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: A Retrospective Study From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2009; 27: 3951–3958.

    PubMed  PubMed Central  Google Scholar 

  125. 125

    Le Gouill S, Milpied N, Buzyn A, De Latour RP, Vernant JP, Mohty M et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol 2008; 26: 2264–2271.

    PubMed  PubMed Central  Google Scholar 

  126. 126

    Dodero A, Spina F, Narni F, Patriarca F, Cavattoni I, Benedetti F et al. Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect. Leukemia 2012; 26: 520–526.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. 127

    Bradford PT, Devesa SS, Anderson WF, Toro JR . Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood 2009; 113: 5064–5073.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128

    Whittaker SJ, Marsden JR, Spittle M, Russell-Jones R . Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Groups guidelines for the management of primary cutaneous T-cell lymphomas. Br J Dermatol 2003; 149: 1095–1107.

    CAS  PubMed  Google Scholar 

  129. 129

    Horwitz SM, Olsen EA, Duvic M, Porcu P, Kim YH . Review of the treatment of mycosis fungoides and sezary syndrome: a stage-based approach. J Natl Compr Canc Net 2008; 6: 436–442.

    Google Scholar 

  130. 130

    Benton EC, Crichton S, Talpur R, Agar NS, Fields PA, Wedgeworth E et al. A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome. Eur J Cancer 2013; 49: 2859–2868.

    CAS  PubMed  Google Scholar 

  131. 131

    Duarte RF, Schmitz N, Servitje O, Sureda A . Haematopoietic stem cell transplantation for patients with primary cutaneous T-cell lymphoma. Bone Marrow Transplant 2008; 41: 597–604.

    CAS  PubMed  Google Scholar 

  132. 132

    Duarte RF, Canals C, Onida F, Gabriel IH, Arranz R, Arcese W et al. Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2010; 28: 4492–4499.

    PubMed  Google Scholar 

  133. 133

    Duarte RF, Boumendil A, Onida F, Gabriel I, Arranz R, Arcese W et al. Long-term outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and sézary syndrome: a European society for blood and marrow transplantation lymphoma working party extended analysis. J Clin Oncol. 2014; 32: 3347–3348.

    PubMed  Google Scholar 

  134. 134

    Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet 1993; 341: 1051–1054.

    CAS  Google Scholar 

  135. 135

    Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet 2002; 359: 2065–2071.

    CAS  Google Scholar 

  136. 136

    Martinez C, Canals C, Sarina B, Alessandrino EP, Karakasis D, Pulsoni A et al. Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation. Ann Oncol 2013; 24: 2430–2434.

    CAS  PubMed  Google Scholar 

  137. 137

    Van Den Neste E, Casasnovas O, Andre M, Touati M, Senecal D, Edeline V et al. Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant. Haematologica 2013; 98: 1185–1195.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138

    Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M et al. Allogeneic stem cell transplantation after reduced intensityconditioning in patients with relapsed or refractory Hodgkin'slymphoma. Results of the HDR-ALLO study—a prospectiveclinical trial by the Grupo Espanol de Linfomas/ Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party ofthe European Group for Blood and Marrow Transplantation. Haematologica 2012; 97: 310–317.

    PubMed  PubMed Central  Google Scholar 

  139. 139

    Sarina B, Castagna L, Farina L, Patriarca F, Benedetti F, Carella AM et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood 2010; 115: 3671–3677.

    CAS  Google Scholar 

  140. 140

    Messer M, Steinzen A, Vervolgyi E, Lerch C, Richter B, Dreger P et al. Unrelated and alternative donor allogeneic stem cell transplantation in patients with relapsed or refractory Hodgkin's lymphoma: a systematic review. Leuk Lymphoma 2014; 55: 296–306.

    CAS  PubMed  Google Scholar 

  141. 141

    Marcais A, Porcher R, Robin M, Mohty M, Michalet M, Blaise D et al. Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin's lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Haematologica 2013; 98: 1467–1475.

    PubMed  PubMed Central  Google Scholar 

  142. 142

    Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1782–1791.

    CAS  Google Scholar 

  143. 143

    McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1770–1781.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144

    Jimenez-Zepeda VH, Mikhael J, Winter A, Franke N, Masih-Khan E, Trudel S et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transplant 2012; 18: 773–779.

    PubMed  PubMed Central  Google Scholar 

  145. 145

    Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007; 356: 1110–1120.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. 146

    Gahrton G, Iacobelli S, Bjorkstrand B, Hegenbart U, Gruber A, Greinix H et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood 2013; 121: 5055–5063.

    CAS  Google Scholar 

  147. 147

    Rosinol L, Perez-Simon JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ et al. A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 2008; 112: 3591–3593.

    CAS  PubMed  PubMed Central  Google Scholar 

  148. 148

    Patriarca F, Einsele H, Spina F, Bruno B, Isola M, Nozzoli C et al. Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 2012; 18: 617–626.

    CAS  PubMed  Google Scholar 

  149. 149

    Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med 2007; 357: 1083–1093.

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150

    Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009; 147: 43–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. 151

    Scheinberg P, Young NS . How I treat acquired aplastic anemia. Blood 2012; 120: 1185–1196.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. 152

    EBMT 2012 Handbook, 6th Edition, available at

  153. 153

    Bacigalupo A, Socié G, Schrezenmeier H, Tichelli A, Locasciulli A, Fuehrer M et al. Bone marrow versus peripheral blood matched sibling transplants, in acquired aplastic anemia: survival advantage for marrow in all age groups. Haematologica 2012; 97: 1142–1148.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154

    Bacigalupo A, Marsh JC . Unrelated donor search and unrelated donor transplantation in the adult aplastic anaemia patient aged 18-40 years without an HLA-identical sibling and failing immunosuppression. Bone Marrow Transplant 2013; 48: 198–200.

    CAS  Google Scholar 

  155. 155

    Marsh JC, Gupta V, Lim Z, Ho AY, Ireland RM, Hayden J et al. Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anaemia. Blood 2011; 118: 2351–2357.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. 156

    Marsh JC, Pearce RM, Koh MB, Lim Z, Pagliuca A, Mufti GJ et al. Retrospective study of Alemtuzumab versus ATG based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anaemia: a study from the British Society for Blood and Marrow Transplantation (BSBMT). Bone Marrow Transplant 2014; 49: 42–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Peffault de Latour R, Purtill D, Ruggeri A, Sanz G, Michel G, Gandemer V et al. Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anaemia. A study by Eurocord and the Aplastic Anaemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2011; 17: 78–85.

    Google Scholar 

  158. 158

    De Latour RP, Rocha V, Socie G . Cord blood transplantation in aplastic anaemia. Bone Marrow Transplant 2013; 48: 201–201.

    Google Scholar 

  159. 159

    Ciceri F, Lupo-Stanghellini MT, Korthof ET . Haploidentical transplantation in patients with acquired aplastic anaemia. Bone Marrow Transplantation 2013; 48: 183–185.

    CAS  PubMed  Google Scholar 

  160. 160

    Clay J, Kulasekarara AG, Potter V, Grimaldi F, McLornan D, Raj K et al. Non-myeloablative peripheral blood haploidentical stem cell transplantation for refractory severe aplastic anemia. Biol Blood Marrow Transplant 2014; 20: 1711–1716.

    PubMed  PubMed Central  Google Scholar 

  161. 161

    De Latour RP, Schrezenmeier H, Bacigalupo A, Blaise D et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica 2012; 97: 1666–1673.

    PubMed Central  Google Scholar 

  162. 162

    Brodsky RA . Paroxysmal nocturnal hemoglobinuria. Blood 2014; 124: 2804–2811.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. 163

    Medeiros C, Zaris-Neto J, Pasquini R . Bone marrow transplantation for patients with Fanconi anaemia: reduced doses of cyclophosphamide without irradiation as conditioning. Bone Marrow Transplant 1999; 24: 849–852.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. 164

    De Latour RP, Porcher R, Dalle J-H, Aljurf M, Korthof ET, Svahn J et al. Allogeneic haemopoietic stem cell transplantation in Fanconi anaemia: the European Group for Blood and Bone Marrow Transplantation experience. Blood 2013; 122: 4279–4286.

    Google Scholar 

  165. 165

    Gadalla SM, Sales-Bonfim C, Carreras J, Alter BP, Antin JH, Ayas M et al. Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenital. Biol Blood Marrow Transplant 2013; 19: 1238–1243.

    PubMed  PubMed Central  Google Scholar 

  166. 166

    Ayas M, Nassar A, Hamidieh AA, Kharfan-Dabaja M, Othman TB, Elhaddad A et al. Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure. Bone Marrow Transplant 2013; 48: 1168–1172.

    CAS  Google Scholar 

  167. 167

    Martino M, Bottini A, Rosti G, Generali D, Secondino S, Barni S et al. Critical issues on high-dose chemotherapy with autologous hematopoietic progenitor cell transplantation in breast cancer patients. Expert Opin Biol Ther 2012; 12: 1505–1515.

    CAS  PubMed  Google Scholar 

  168. 168

    Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Rodenhuis S et al. High dose chemotherapy with autologous stem cell support versus standard-dose chemotherapy: Overview of individual patient data from 15 randomized adjuvant therapy breast cancer trials. J Clin Oncol 2011; 29: 3214–3223.

    CAS  PubMed  PubMed Central  Google Scholar 

  169. 169

    Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C et al. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre Phase III trial. Lancet 2005; 366: 1935–1944.

    CAS  Google Scholar 

  170. 170

    Rodenhuis S, Bontenbal M, van Hoesel QG, Smit WM, Nooij MA, Voest EE et al. Efficacy of high-dose alkylating chemotherapy in HER2/ neu-negative breast cancer. Ann Oncol 2006; 17: 588–596.

    CAS  PubMed  Google Scholar 

  171. 171

    Pedrazzoli P, Martino M, Delfanti S, Generali D, Bregni M, Lanza F et al. High-dose chemotherapy with autologous hematopoietic stem cell transplantation in high-risk breast cancer patients. J Nat Cancer Inst 2014; 20: 501–506.

    CAS  Google Scholar 

  172. 172

    Martino M, Ballestrero A, Zambelli A, Secondino S, Aieta M, Bengala C et al. Long-term survival in patients with metastatic breast cancer receiving intensified chemotherapy and stem cell rescue: data from the Italian registry. Bone Marrow Transplant 2013; 48: 414–418.

    CAS  PubMed  Google Scholar 

  173. 173

    Simonelli M, Rosti G, Banna GL, Pedrazzoli P . Intensified chemotherapy with stem-cell rescue in germ-cell tumors. Ann Oncol 2012; 23: 815–822.

    CAS  PubMed  Google Scholar 

  174. 174

    Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R . High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 2007; 357: 340–348.

    CAS  PubMed  Google Scholar 

  175. 175

    Beyer J, Albers P, Altena R, Aparicio J, Bokemeyer C, Busch J et al. Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer. Ann Oncol 2013; 24: 878–888.

    CAS  PubMed  Google Scholar 

  176. 176

    Lorch A, Bascoul-Mollevi C, Kramar A, Einhorn L, Necchi A, Massard C et al. Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database. J Clin Oncol 2011; 29: 2178–2184.

    PubMed  Google Scholar 

  177. 177

    Ledermann JA . Lessons learned from a decade of clinical trials of high-dose chemotherapy in ovarian cancer. Int J Gynecol Cancer 2008; 18 (Suppl 1): 53–58.

    PubMed  Google Scholar 

  178. 178

    Leyvraz S, Pampallona S, Martinelli G, Ploner F, Perey L, Aversa S et al. A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial. J Natl Cancer Inst 2008; 100: 533–541.

    CAS  PubMed  Google Scholar 

  179. 179

    Pedrazzoli P, Ledermann JA, Lotz JP, Leyvraz S, Aglietta M, Rosti G et al. High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol 2006; 17: 1479–1488.

    CAS  PubMed  Google Scholar 

  180. 180

    NCCN guidelines version 1Bone cancer 2014.

  181. 181

    Ladenstein R, Pötschger U, Le Deley MC, Whelan J, Paulussen M, Oberlin O et al. Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol 2010; 28: 3284–3291.

    CAS  PubMed  PubMed Central  Google Scholar 

  182. 182

    Spreafico F, Massimino M, Gandola L, Cefalo G, Mazza E, Landonio G et al. Survival of adults treated for medulloblastoma using paediatric protocols. Eur J Cancer 2005; 41: 1304–1310.

    PubMed  Google Scholar 

  183. 183

    Barkholt L, Bregni M, Remberger M, Blaise D, Peccatori J, Massenkeil G et al. Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe. Ann Oncol 2006; 17: 1134–1140.

    CAS  PubMed  Google Scholar 

  184. 184

    Thiel U, Koscielniak E, Blaeschke F, Grunewald TG, Badoglio M, Diaz MA et al. Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment. Br J Cancer 2013; 109: 2523–2532.

    CAS  PubMed  PubMed Central  Google Scholar 

  185. 185

    Carnevale-Schianca F, Cignetti A, Capaldi A, Vitaggio K, Vallario A, Ricchiardi A et al. Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD. Blood 2006; 107: 3795–3803.

    CAS  PubMed  Google Scholar 

  186. 186

    Demirer T, Barkholt L, Blaise D, Pedrazzoli P, Aglietta M, Carella AM et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Clin Pract Oncol 2008; 5: 256–267.

    CAS  Google Scholar 

  187. 187

    Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive mieloablative chemoradiation preparative regimens. J Clin Oncol 2008; 26: 5233–5239.

    CAS  PubMed  PubMed Central  Google Scholar 

  188. 188

    Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29: 917–924.

    PubMed  PubMed Central  Google Scholar 

  189. 189

    Comoli P, Pedrazzoli P, Maccario R, Basso S, Carminati O, Labirio M et al. Cell therapy of stage IV nasopharyngeal carcinoma with autologous EBV-targeted cytotoxic T-lymphocytes. J Clin Oncol 2005; 23: 8942–8949.

    CAS  Google Scholar 

  190. 190

    Pedrazzoli P, Comoli P, Montagna D, Demirer T, Bregni M . Is adoptive T-cell therapy for solid tumors coming of age? Bone Marrow Transplant 2012; 47: 1013–1019.

    CAS  PubMed  Google Scholar 

  191. 191

    Van Laar J, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J et al. Autologous hematopoietic stem cell transplantation versus intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 2014; 311: 2490–2498.

    CAS  PubMed  Google Scholar 

  192. 192

    Saccardi R, Freedman MS, Sormani MP, Atkins H, Farge D, Griffith LM et al. A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper. Mult Scler 2012; 18: 825–834.

    CAS  PubMed  PubMed Central  Google Scholar 

  193. 193

    Mancardi G, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E et al. Autologous Haematopoietic Stem Cell Transplantation in Multiple Sclerosis: a phase II trial. Neurology 2015 (e-pub ahead of print).

  194. 194

    Burt RK, Oliveira MC, Shah SJ, Moraes DA, Simoes B, Gheorghiade M et al. Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis. Lancet 2013; 381: 1116–1124.

    PubMed  Google Scholar 

  195. 195

    Creutzig U, Zimmermann M, Dworzak MN, Ritter J, Schellong G, Reinhardt D . Development of a curative treatment within the AML-BFM studies. Klinische Padiatrie 2013; 225 (Suppl 1): S79–S86.

    PubMed  Google Scholar 

  196. 196

    Creutzig U, Zimmermann M, Ritter J, Henze G, Graf N, Loffler H et al. Definition of a standard-risk group in children with AML. Br J Haematol 1999; 104: 630–639.

    CAS  PubMed  Google Scholar 

  197. 197

    Niewerth D, Creutzig U, Bierings MB, Kaspers GJ . A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood 2010; 116: 2205–2214.

    CAS  PubMed  PubMed Central  Google Scholar 

  198. 198

    Burke MJ, Wagner JE, Cao Q, Ustun C, Verneris MR . Allogeneic hematopoietic cell transplantation in first remission abrogates poor outcomes associated with high-risk pediatric acute myeloid leukemia. Biol Blood Marrow Transplant 2013; 19: 1021–1025.

    PubMed  PubMed Central  Google Scholar 

  199. 199

    Klusmann JH, Reinhardt D, Zimmermann M, Kremens B, Vormoor J, Dworzak M et al. The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study. Haematologica 2012; 97: 21–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  200. 200

    Creutzig U, Zimmermann M, Bourquin JP, Dworzak MN, Kremens B, Lehrnbecher T et al. Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report. Leukemia 2012; 26: 654–661.

    CAS  PubMed  Google Scholar 

  201. 201

    Marks D, Khattry N, Cummins M, Goulden N, Green A, Harvey J et al. Haploidentical stem cell transplantation for children with acute leukaemia. Br J Haematol 2006; 134: 196–201.

    PubMed  PubMed Central  Google Scholar 

  202. 202

    Locatelli F, Pende D, Maccario R, Mingari MC, Moretta A, Moretta L . Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference. Clin Immunol 2009; 133: 171–178.

    CAS  PubMed  PubMed Central  Google Scholar 

  203. 203

    Hasle H . A critical review of which children with acute myeloid leukaemia need stem cell procedures. Br J Haematol 2014; 166: 23–33.

    PubMed  Google Scholar 

  204. 204

    Pulsipher MA, Peters C, Pui CH . High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant? Biol Blood Marrow Transplant 2011; 17 (1 Suppl): S137–S148.

    PubMed  PubMed Central  Google Scholar 

  205. 205

    Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol 2009; 27: 377–384.

    PubMed  PubMed Central  Google Scholar 

  206. 206

    Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grumayer R et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol 2013; 31: 2736–2742.

    PubMed  Google Scholar 

  207. 207

    Mann G, Attarbaschi A, Schrappe M, De Lorenzo P, Peters C, Hann I et al. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. Blood 2010; 116: 2644–2650.

    CAS  PubMed  Google Scholar 

  208. 208

    von Stackelberg A, Volzke E, Kuhl JS, Seeger K, Schrauder A, Escherich G et al. Outcome of children and adolescents with relapsed acute lymphoblastic leukaemia and non-response to salvage protocol therapy: a retrospective analysis of the ALL-REZ BFM Study Group. Eur J Cancer 2011; 47: 90–97.

    PubMed  Google Scholar 

  209. 209

    Peters C, Cornish JM, Parikh SH, Kurtzberg J . Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia. Pediat Clin North America 2010; 57: 27–46.

    Google Scholar 

  210. 210

    Schrauder A, von Stackelberg A, Schrappe M, Cornish J, Peters C . Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials. Bone Marrow Transplant 2008; 41 (Suppl 2): S71–S74.

    PubMed  Google Scholar 

  211. 211

    Beck JC, Cao Q, Trotz B, Smith AR, Weigel BJ, Verneris MR et al. Allogeneic hematopoietic cell transplantation outcomes for children with B-precursor acute lymphoblastic leukemia and early or late BM relapse. Bone Marrow Transplant 2011; 46: 950–955.

    CAS  PubMed  Google Scholar 

  212. 212

    Meisel R, Klingebiel T, Dilloo D . German/Austrian Pediatric Registry for Stem Cell Transplantation. Peripheral blood stem cells versus bone marrow in pediatric unrelated donor stem cell transplantation. Blood 2013; 121: 863–865.

    CAS  PubMed  Google Scholar 

  213. 213

    Burkhardt B, Reiter A, Landmann E, Lang P, Lassay L, Dickerhoff R et al. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group. J Clin Oncol 2009; 27: 3363–3369.

    PubMed  Google Scholar 

  214. 214

    Gross TG, Hale GA, He W, Camitta BM, Sanders JE, Cairo MS et al. Hematopoietic stem cell transplantation for refractory or recurrent non-Hodgkin lymphoma in children and adolescents. Biol Blood Marrow Transplant 2010; 16: 223–230.

    Google Scholar 

  215. 215

    Woessmann W, Peters C, Lenhard M, Burkhardt B, Sykora KW, Dilloo D et al. Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents—a Berlin-Frankfurt-Munster group report. Br J Haematol 2006; 133: 176–182.

    PubMed  PubMed Central  Google Scholar 

  216. 216

    Jaeger BA, Tauer JT, Ulmer A, Kuhlisch E, Roth HJ, Suttorp M . Changes in bone metabolic parameters in children with chronic myeloid leukemia on imatinib treatment. Med Sci Monit 2012; 18: 721–728.

    Google Scholar 

  217. 217

    Ulmer A, Tabea Tauer J, Glauche I, Jung R, Suttorp M . TK inhibitor treatment disrupts growth hormone axis: clinical observations in children with CML and experimental data from a juvenile animal model. Klinische Padiatrie 2013; 225: 120–126.

    CAS  PubMed  Google Scholar 

  218. 218

    Suttorp M, Claviez A, Bader P, Peters C, Gadner H, Ebell W et al. Allogeneic stem cell transplantation for pediatric and adolescent patients with CML: results from the prospective trial CML-paed I. Klinische Padiatrie 2009; 221: 351–357.

    CAS  PubMed  Google Scholar 

  219. 219

    Suttorp M, Eckardt L, Tauer JT, Millot F . Management of chronic myeloid leukemia in childhood. Current Hematologic Malignancy Reports 2012; 7: 116–124.

    PubMed  Google Scholar 

  220. 220

    Suttorp M, Yaniv I, Schultz KR . Controversies in the treatment of CML in children and adolescents: TKIs versus BMT? Biol Blood Marrow Transplant 2011; 17 (1 Suppl): S115–S122.

    PubMed  PubMed Central  Google Scholar 

  221. 221

    de la Fuente J, Baruchel A, Biondi A, de Bont E, Dresse MF, Suttorp M, Millot F . Managing children with chronic myeloid leukaemia (CML): Recommendations for the management of CML in children and young people up to the age of 18 years. Br J Haematol 2014; 167: 33–47.

    PubMed  Google Scholar 

  222. 222

    Millot F, Claviez A, Leverger G, Corbaciglu S, Groll AH, Suttorp M . Imatinib cessation in children and adolescents with chronic myeloid leukemia in chronic phase. Pediatr Blood Cancer 2014; 61: 355–357.

    PubMed  Google Scholar 

  223. 223

    Locatelli F, Crotta A, Ruggeri A, Eapen M, Wagner JE, Macmillan ML et al. Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: a EUROCORD, EBMT, EWOG-MDS, CIBMTR study. Blood 2013; 122: 2135–2141.

    CAS  PubMed  PubMed Central  Google Scholar 

  224. 224

    Madureira AB, Eapen M, Locatelli F, Teira P, Zhang MJ, Davies SM et al. Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation. Leukemia 2011; 25: 449–454.

    CAS  PubMed  Google Scholar 

  225. 225

    Strahm B, Nollke P, Zecca M, Korthof ET, Bierings M, Furlan I et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia 2011; 25: 455–462.

    CAS  PubMed  PubMed Central  Google Scholar 

  226. 226

  227. 227

    Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG et al. Neonatal diagnosis of Severe Combined Immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood 2011; 117: 3243–3246.

    CAS  PubMed  Google Scholar 

  228. 228

    Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P et al. Transplantation of haematopoietic stem cells and long term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol 2010; 126: 602–610.

    PubMed  Google Scholar 

  229. 229

    Boelens JJ, Aldenhoven M, Purtill D, Ruggeri A, Defor T, Wynn R et al. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood 2013; 121: 3981–3987.

    CAS  PubMed  PubMed Central  Google Scholar 

  230. 230

    Samarasinghe A, Webb DK . How I manage aplastic anaemia in children. Br J Haematol 2012; 157: 26–40.

    CAS  PubMed  Google Scholar 

  231. 231

    Samarasinghe S, Steward C, Hiwarkar P, Saif MA, Hough R, Webb D et al. Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience. Br J Haematol 2012; 157: 339–436.

    CAS  Google Scholar 

  232. 232

    Bhatnagar N, Wynn RF, Velangi M et al. Upfront matched and mismatched unrelated donor transplantation in paediatric idiopathic severe aplastic anaemia: A United Kingdom multicentre retrospective experience. Bone Marrow Transplant 2014; 49 (S1): 0004a.

    Google Scholar 

  233. 233

    Samarasinghe S, Marsh J, Dufour C . Immune suppression for childhood acquired aplastic anemia and myelodysplastic syndrome: where next? Haematologica 2014; 99: 597–599.

    CAS  PubMed  PubMed Central  Google Scholar 

  234. 234

    Dufour C, Pillon M, Carraro E, Bhatnagar N, Wynn R, Gibson B et al. Similar outcome of upfront unrelated and matched sibling donor hematopoietic stem cell transplantation in idiopathic aplastic anaemia of childhood and adolescence: A cohort controlled study on behalf of the UK Paediatric BMT Working Party of the Paediatric Diseases Working Party and of the Severe Aplastic Anaemia WP of the EBMT. Blood, Annual Scientific Meeting 2014, 256a.

  235. 235

    Fagioli F, Quarello P, Zecca M, Lanino E, Corti P, Favre C et al. Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry. Br J Haematol 2014; 165: 673–681.

    PubMed  Google Scholar 

  236. 236

    Locatelli F, Kabbara N, Ruggeri A, Ghavamzadeh A, Roberts I, Li CK et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood 2013; 122: 1072–1078.

    CAS  PubMed  Google Scholar 

  237. 237

    Gaziev J, Marziali M, Isgro A, Sodani P, Paciaroni K, Gallucci C et al. Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach. Blood 2013; 122: 2751–2756.

    CAS  Google Scholar 

  238. 238

    Lucarelli G, Isgro A, Sodani P, Gaziev J . Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia. Cold Spring Harb Perspect Med 2012; 2: a011825.

    PubMed  PubMed Central  Google Scholar 

  239. 239

    Galambrun C, Pondarre C, Bertrand Y, Loundou A, Bordigoni P, Frange P et al. French multicenter 22 year-experience of Stem Cell transplantation for Beta-Thalassemia Major: lessons and future directions. Biol Blood Marrow Transplant. 2013; 19: 62–68.

    PubMed  Google Scholar 

  240. 240

    Angelucci E, Baronciani D . Allogeneic stem cell transplantation for thalassemia major. Haematologica 2008; 93: 1780–1784.

    PubMed  Google Scholar 

  241. 241

    Matthes-Martin S, Lawitschka A, Fritsch G, Lion T, Grimm B, Breuer S et al. Stem cell transplantation after reduced-intensity conditioning for sickle cell disease. Eur J Haematol 2013; 90: 308–312.

    PubMed  Google Scholar 

  242. 242

    Lucarelli G, Gaziev J, Isgro A, Sodani P, Paciaroni K, Alfieri C et al. Allogeneic cellular gene therapy in hemoglobinopathies—evaluation of hematopoietic SCT in sickle cell anemia. Bone Marrow Transpl 2012; 47: 227–230.

    CAS  Google Scholar 

  243. 243

    Kamani NR, Walters MC, Carter S, Aquino V, Brochstein JA, Chaudhury S et al. Unrelated donor cord blood transplantation for children with severe sickle cell disease: Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biol Blood Marrow Transplant 2012; 18: 1265–1272.

    PubMed  PubMed Central  Google Scholar 

  244. 244

    Fernandes JF, Rocha V, Labopin M, Neven B, Moshous D, Gennery AR et al. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood 2012; 119: 2949–2955.

    CAS  PubMed  Google Scholar 

  245. 245

    Ladenstein R, Potschger U, Hartman O, Pearson AD, Klingebiel T, Castel V et al. 28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures. Bone Marrow Transplant 2008; 41 (Suppl 2): S118–S127.

    CAS  Google Scholar 

  246. 246

    Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol 2009; 27: 1007–1013.

    CAS  PubMed  PubMed Central  Google Scholar 

  247. 247

    Patel JP, Levine RL . How do novel molecular genetic markers influence treatment decisions in acute myeloid leukemia? Hematology Am Soc Hematol Educ Program 2012; 2012: 28–34.

    PubMed  Google Scholar 

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We are grateful for the advice and helpful comments received from a number of individuals across Europe specializing in the use of haematopoietic SCT. Special thanks to L. Garderet, O. Hermine, S, Montoto, E. Olavarria, S. Robinson, J. Schetelig, N. Schmitz, H. Schouten and A. Tanase.

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Sureda, A., Bader, P., Cesaro, S. et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant 50, 1037–1056 (2015).

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