We report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reduced-intensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was 53 years (range 21–72 years). A total of 49 (38%) recipients had a sibling donor and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was assigned to all patients with a score of 0 in 40 (31%), of 1–2 in 45 (35%) and ⩾3 in 43 (34%) patients. The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was 41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI score of 0, 1–2 or ⩾3 was 16, 24 and 42%, respectively. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1–2) and 24 and 32% (score ⩾3), respectively. On multivariate analysis, HCT-CI was an independent variable affecting 3-year NRM, DFS and OS (P-value=0.04, 0.01 and <0.01, respectively). Although the disease stage at the time of transplant was an additional independent predictive variable on transplant outcomes, recipient age (>/<50 years) did not have a significant predictive impact. In MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of stratifying patients with a high risk of inferior transplant outcomes.
Allogeneic hematopoietic SCT (allo-HSCT) offers a potentially curative option for patients with poor-risk myelodysplastic syndrome (MDS) and AML. The majority of patients with AML and MDS are older, and many present with associated comorbidity rendering them ineligible for myeloablative approaches. More recently, a significant reduction in regimen-related toxicity and non-relapse mortality (NRM) with reduced-intensity conditioning (RIC) regimens has enabled allogeneic transplantation to be extended to this group of patients.1, 2, 3, 4, 5, 6 Despite these advances, transplant-related morbidity and mortality, particularly in elderly patients with advanced disease, remain significant.
There is a need to improve the characterization of patient- and transplant-specific variables that potentially predict outcome to improve survival after allo-HSCT.7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Recent literature has indicated that performance status of transplant recipients, rather than recipient age per se, may be a better indicator of the ability of a patient to tolerate allo-HSCT. The Charlson comorbidity index, adapted for HSCT, has been shown to predict NRM in patients receiving allogeneic HSCT. In the setting of HLA-matched sibling allo-HSCT, it has been shown that a high Charlson comorbidity index correlates with inferior outcomes in patients receiving either myeloablative or non-myeloablative allo-HSCT.17 This association was also observed in recipients of unrelated donor transplants regardless of regimen intensity.18 Sorror et al. have reported on the utility of a hematopoietic cell transplantation-specific comorbidity index (HCT-CI). In a validation study with 1055 recipients of T-cell-replete myeloablative or non-myeloablative allogeneic transplantation, the HCT-CI was shown to correlate with both NRM and overall survival (OS).19 More recently, the same group has shown in a risk stratification-based study that the use of disease risk status together with the HCT-CI provided improved prognostic delineation of patients with AML or MDS receiving allogeneic HSCT. In particular, in patients with high-risk disease MDS or AML undergoing RIC HSCT, patients with an HCT-CI of ⩾3 had a 2-year OS of only 29%.20
Various groups have used in vivo T-cell depletion with either alemtuzumab (Campath-1H) or anti-thymocyte globulin to lower the incidence of both acute GVHD (aGVHD) and chronic GVHD (cGVHD)6, 21, 22, 23, 24, 25 with the aim of reducing NRM.
There are presently limited data available on the utility of the HCT-CI in the setting of T-cell-depleted RIC HSCT, and it remains unclear as to whether the HCT-CI has a similar prognostic utility in this setting. Herein, we report a retrospective analysis of 128 consecutive patients with high-risk MDS and AML who received T-cell-depleted RIC allo-HSCT from sibling and volunteer donors to determine the predictive value of the HCT-CI on overall transplant outcomes.
Patients and methods
We performed a single-center analysis of 128 consecutive patients with poor-risk MDS and AML treated between 1999 and 2005. The median recipient age was 53 years (range 21–72 years). The diagnostic criteria were defined according to the World Health Organization classification.26 All patients had advanced disease as defined by MDS (RAEB I or II) or AML (CR2 or greater). Cytogenetic risk was assigned to MDS patients in accordance with the international prognostic scoring system and to AML patients according to the UK MRC AML risk stratification.27, 28 Poor-risk cytogenetics were identified in 27% of patients. The median number of cycles of chemotherapy administered pretransplant was 3 (range 1–9) for the AML group and 2 (range 0–9) for the MDS group.
The RIC regimen consisted of fludarabine (150 mg/m2 i.v. in divided doses over 5 days from days −9 to −5), BU (8 mg/kg orally over 2 days on days −3 and −2) and alemtuzumab (100 mg i.v. over 5 days from day −8 to −4) (FBC) in 95 patients, FBC with i.v. BU (6.4 mg/kg i.v. over 2 days) in 32 patients, and fludarabine (150 mg/m2 i.v. over 5 days), melphalan (140 mg/m2 i.v.) and alemtuzumab (100 mg i.v. over 5 days) (FMC) in 1 patient. CYA was administered for GVHD prophylaxis, commenced at day −1 and tapered from day +56 in the absence of GVHD. The indication for RIC included age >50 years (n=84), invasive pulmonary aspergillosis within 3 months of transplant (n=24), impaired organ function (n=43), earlier autologous HSCT (n=6) and iron overload (n=1). In total, 30 patients had more than one relative contraindication for myeloablative conditioning.
All donor–recipient pairs were matched for HLA-A, -B, -C, -DRB1 and DQB1 by high-resolution allelic testing. A sibling donor was used in 49 (38%) and volunteer-unrelated donor (VUD) in 79 (62%) transplants, with a 1 Ag mismatch donor in 29 patients (17 HLA class 1 mismatch and 12 HLA class 2 mismatch). A further five patients received stem cells from a two Ag mismatch donor. PBSCs were administered to 95 (74%) patients. Standard nursing care and post-transplant prophylaxis were administered as described earlier.6
The HCT-CI was used to assign a pretransplant comorbidity score to all patients.19 A score of 0 was identified in 40 (31%), score 1 in 23 (18%), score 2 in 22 (17%) and ⩾3 in 43 (34%) patients. The most frequent comorbidities identified were a reduction in pulmonary diffusion capacity <80% (n=46) or cardiac ejection fraction <50% (n=14), infection requiring treatment after day 0 (n=20), ischemic heart disease (n=2), arrhythmia (n=2), renal dysfunction (n=2) and other comorbidity (n=12).
Differences between patient groups were evaluated using the χ2-test for categorical data, and the Mann–Whitney test for continuous data. OS and relapse-free survival curves were estimated by the Kaplan–Meier method in the entire study population and in univariate analysis (the log-rank test was used to compare survival curves between different subgroups).
To calculate relapse incidence, NRM and the incidence of aGVHD and cGVHD, a competing risk model was used. In each case, death (before the event under study) was used as the competing event (NRM was therefore derived from the relapse-competing risk analysis). The effect of any possible risk factor on either relapse or NRM was still estimated by using a Cox model where relapse was treated as a censoring event for the end point ‘death’ and vice versa.
The Cox proportional hazards model was used to assess the independent effect of age, sex, disease group (MDS vs AML), HCT-CI (0 vs 1–2 vs ⩾3), cytogenetic risk, disease status at time of transplant (CR vs active disease), donor type (sibling vs VUD), HLA disparity, source of stem cells (PBSC vs BM), as well as stem cell dose on transplant outcomes. On multivariate analysis, independent variables with P>0.1 were sequentially excluded from the model. The P-value was set at P<0.05 for statistical significance.
Neutrophil and plt engraftment were defined as neutrophils >0.5 × 109 per liter on the first two consecutive days and plts >20 × 109 per liter for 5 days without transfusions. The median time to neutrophil and plt engraftment was 13 days (range 8–57 days) and 18 days (range 0–121 days), respectively. Primary graft failure was identified in 4 (3%) patients.
There were 33 deaths attributable to NRM. The cumulative incidence of NRM at 1 and 3 years was 25 and 31%, respectively. NRM was caused by to GVHD in 4 patients, bacterial infection in 13, viral infection in 11, multiorgan failure in 2, veno-occlusive disease of the liver in 1 and by other causes in 2 patients.
On univariate analysis (Table 1), both disease status at transplant and HCT-CI significantly influenced the NRM. An advanced disease status was associated with an inferior NRM when compared with early disease status (3-year TRM: 50 vs 28%, P<0.01). The 3-year NRM for patients with an HCT-CI score of 0, 1–2 or ⩾3 was 16, 24 and 42%, respectively (Figure 1a). However, although patients with an HCT-CI score of ⩾3 had a significantly worse NRM (P=0.02) when compared with those with an HCT-CI score of 0, there was no significant difference in the NRM between patients with a score of 1–2 and those with either an HCT-CI score of 0 (P=0.33) or a score ⩾3 (P=0.11). In addition, recipient age, donor source (sibling vs VUD) and the presence of HLA disparity had no influence on NRM.
On multivariate analysis (Table 2), disease status at transplant and HCT-CI were independent variables predicting NRM. The hazard ratio (HR) for NRM was 2.70 (95% CI 1.25–5.83, P=0.01) for those with advanced disease at the time of transplant when compared with those with early disease. When compared with patients with an HCT-CI of 0, the HR was 1.72 (95% CI 0.64–4.67) for those with an HCT-CI of 1–2 and 3.18 (95% CI 1.24–8.17) for those with an HCT-CI ⩾3.
The cumulative incidence of Grade II–IV aGVHD was 30%, with the specific incidence of grade IV as 2%. Patients surviving at least 100 days post transplant were analyzed for cGVHD. The cumulative incidence of chronic limited GVHD at 3 years was 23%, with an incidence of chronic extensive GVHD of 15%. There was no correlation between the HCT-CI score and GVHD.
OS and DFS
The median follow-up of the study group was 2.8 years (range 0.5–6.1 years). The 3-year disease-free survival (DFS) was 41% and OS was 46%. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1–2), and 24 and 32% (score ⩾3), respectively. Figure 1 shows the effect of HCT-CI on DFS and OS, respectively. Patients with HCT-CI scores of 1–2 and ⩾3 had a significantly inferior OS to patients with an HCT-CI score of 0 (P<0.01, P<0.01, respectively). However, there was no statistically significant difference in OS between HCT-CI scores 1–2 and ⩾3 (P=0.52). A similar association was seen in DFS (score 0 vs 1–2, P=0.03), (score 0 vs ⩾3, P<0.01) and (score 1–2 vs ⩾3, P=0.35).
On multivariate analysis, HCT-CI was an independent variable affecting both DFS and OS (P=0.01 and P<0.01, respectively). Advanced disease at the time of transplant also showed an adverse effect on OS in the multivariate model (HR: 1.96, 95% CI 1.08–3.56; P=0.03). Advanced recipient age (> 50 years) did not have a significant influence on DFS (HR 1.55, 95% CI 0.92–2.61; P=0.10) and had only a borderline significant influence on OS (HR 1.78, 95% CI 1.00–3.14; P=0.05) in the multivariate analysis.
The use of RIC regimens and improved supportive care has enabled allogeneic HSCT to be carried out in older patients with comorbidities. Regardless of the intensity of conditioning or the variation in transplant regimens used, only modest differences in OS have been reported.29, 30, 31, 32 Additional improvements in transplant outcomes may, however, be achieved through identification of prognostic variables and improved patient selection. Reduced-intensity regimens are frequently used in patients with comorbidities. However, formal analysis of these comorbidities on transplant outcome is rarely performed.19, 21, 33 The HCT-CI was specifically developed for use in recipients of HSCT whereby it showed an improved predictive value in identifying patients receiving myeloablative and non-myeloablative HSCT who had a subsequent inferior NRM and survival.19 There is, however, a lack of data on the use of comorbidity scores in the T-cell-depleted allo-HSCT setting.
We have previously described the impact of the HCT-CI on the outcomes of a cohort of MDS patients (with both high- and low-risk disease) receiving an unrelated donor alemtuzumab-based RIC allo-HSCT,23 with no association between the HCT-CI and NRM and only a borderline association with OS. This study includes 31 patients from the previous report, but focuses on high-risk MDS and AML patients who have received an alemtuzumab-based RIC allo-HSCT from either a sibling or an unrelated donor.
A high HCT-CI score of 2 or more was observed in 51% of our cohort of patients, with the most frequent comorbidities being impairment of the pulmonary or cardiac function at the time of transplant and infection requiring treatment with antimicrobial agents at day 0 of transplant. Although the cohort with an HCT-CI score of 1–2 did not have a significantly inferior NRM when compared with the HCT-CI score 0 patients in our study, an HCT-CI score of ⩾3 correlated with a significantly increased risk of NRM (42% at 3 years), consistent with previously reported analyses of non-T-cell-depleted transplant cohorts.19 This indicates that the HCT-CI identifies a distinct cohort of patients (HCT-CI ⩾3) at the highest risk of transplant-related mortality. Taking into account the substantial treatment-related mortality of this sub-cohort, and in view of the recent emergence of several novel therapeutic agents in the treatment of both MDS and AML, prospective clinical studies are required to reassess the role of allogeneic HSCT in patients with high-risk disease and high comorbidities.
In addition, the HCT-CI was able to distinguish cohorts of patients with HCT-CI scores of 1–2 and ⩾3, who had a significantly inferior DFS and OS when compared with patients with no overt comorbidities (HCT-CI score 0). However, unlike the observations within non-T-cell-depleted allo-HSCT, there was no significant difference in either DFS or OS when comparing recipients with an HCT-CI score of 1–2 and those with a higher score of 3. This suggests that the HCT-CI score is a less specific predictor of disease-free and OS in alemtuzumab-treated patients. These observations could in part be explained by the fact that, owing to the high disease risk of the cohort, there was no significant difference in relapse incidence between any of the HCT-CI subgroups of patients.
The association between older age and inferior outcome is well documented in the literature, in particular with myeloablative conditioning.9, 24, 34, 35, 36 However, a number of recent studies of RIC allo-HSCT have shown age to not be a significant factor affecting outcome.5, 23, 32, 37 In this study, although an advanced recipient age of more than 50 years showed an independent correlation with poorer OS (P=0.05), the use of the HCT-CI seemed to be a much stronger predictor of post-transplant outcomes.
We report a low incidence of grade IV aGVHD (2%) within a cohort of patients in which a high proportion (62%) received VUD stem cells. In addition, the cumulative incidence of limited and extensive cGVHD was low at 23 and 15%, respectively, of the patients. Conversely, within this cohort of patients with advanced disease, alemtuzumab was associated with a higher relapse rate, reported at 38% at 3 years. A high incidence of viral complications has also been reported with the use of T-cell depletion.4, 38 Death due to viral illness occurred in 11 (23%) patients who died as a result of NRM: CMV pneumonitis (n=4), adenovirus (n=3), hepatitis B (n=1) and respiratory virus (n=3).
This study confirms observations from several other studies that disease burden at the time of transplantation is one of the most important predictors of outcome.12, 32, 39, 40, 41 The presence of active disease at the time of transplantation remained the strongest predictor of inferior transplant outcome, indicating that this cohort of patients should be considered for alternative therapeutic strategies. The role of dose-escalated conditioning regimens or sequential chemotherapy followed by RIC HSCT has been investigated by other groups in this context, with promising results.42
In summary, this retrospective analysis shows that in MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of identifying patients with a high risk of inferior transplant outcome. New therapeutic strategies need to be developed for patients with high-risk disease and increased comorbidities.
Conflict of interest
The authors declare no conflict of interest.
Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.
McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.
Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 2002; 99: 1071–1078.
Wong R, Giralt SA, Martin T, Couriel DR, Anagnostopoulos A, Hosing C et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood 2003; 102: 3052–3059.
Ho AY, Pagliuca A, Kenyon M, Parker JE, Mijovic A, Devereux S et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood 2004; 104: 1616–1623.
de Witte T, Hermans J, Vossen J, Bacigalupo A, Meloni G, Jacobsen N et al. Haematopoietic stem cell transplantation for patients with myelo-dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2000; 110: 620–630.
Sierra J, Perez WS, Rozman C, Carreras E, Klein JP, Rizzo JD et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood 2002; 100: 1997–2004.
Arnold R, de Witte T, van Biezen A, Hermans J, Jacobsen N, Runde V et al. Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group. Bone Marrow Transplant 1998; 21: 1213–1216.
Castro-Malaspina H, Harris RE, Gajewski J, Ramsay N, Collins R, Dharan B et al. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood 2002; 99: 1943–1951.
Anderson JE, Appelbaum FR, Schoch G, Gooley T, Anasetti C, Bensinger WI et al. Allogeneic marrow transplantation for myelodysplastic syndrome with advanced disease morphology: a phase II study of busulfan, cyclophosphamide, and total-body irradiation and analysis of prognostic factors. J Clin Oncol 1996; 14: 220–226.
Kebriaei P, Kline J, Stock W, Kasza K, Le Beau MM, Larson RA et al. Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant 2005; 35: 965–970.
Guardiola P, Runde V, Bacigalupo A, Ruutu T, Locatelli F, Boogaerts MA et al. Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood 2002; 99: 4370–4378.
Runde V, de Witte T, Arnold R, Gratwohl A, Hermans J, van Biezen A et al. Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1998; 21: 255–261.
Copelan EA, Penza SL, Elder PJ, Ezzone SA, Scholl MD, Bechtel TP et al. Analysis of prognostic factors for allogeneic marrow transplantation following busulfan and cyclophosphamide in myelodysplastic syndrome and after leukemic transformation. Bone Marrow Transplant 2000; 25: 1219–1222.
Yakoub-Agha I, de La Salmoniere P, Ribaud P, Sutton L, Wattel E, Kuentz M et al. Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. J Clin Oncol 2000; 18: 963–971.
Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004; 104: 1550–1558.
Sorror ML, Maris MB, Storer B, Baron F, Sandmaier BM, Maloney DG et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004; 104: 961–968.
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.
Sorror M, Sandmaier B, Storer B, 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.
van Besien K, Artz A, Smith S, Cao D, Rich S, Godley L et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5728–5738.
Tauro S, Craddock C, Peggs K, Begum G, Mahendra P, Cook G et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol 2005; 23: 9387–9393.
Lim ZY, Ho AY, Ingram W, Kenyon M, Pearce L, Czepulkowski B et al. Outcomes of alemtuzumab-based reduced intensity conditioning stem cell transplantation using unrelated donors for myelodysplastic syndromes. Br J Haematol 2006; 135: 201–209.
Remberger M, Storer B, Ringden O, Anasetti C . Association between pretransplant Thymoglobulin and reduced non-relapse mortality rate after marrow transplantation from unrelated donors. Bone Marrow Transplant 2002; 29: 391–397.
Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.
Jaffe E, S HNL, Stein H, Vardiman JW (eds). WHO Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues IARC Press: Lyon, 2001.
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.
Burnett AK, Wheatley K, Goldstone AH, Stevens RF, Hann IM, Rees JH et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002; 118: 385–400.
Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb HJ et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia 2005; 19: 2304–2312.
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.
Scott BL, Sandmaier BM, Storer B, Maris MB, Sorror ML, Maloney DG et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 2006; 20: 128–135.
Shimoni A, Hardan I, Shem-Tov N, Yeshurun M, Yerushalmi R, Avigdor A et al. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia 2006; 20: 322–328.
Parimon T, Au DH, Martin PJ, Chien JW . A risk score for mortality after allogeneic hematopoietic cell transplantation. Ann Intern Med 2006; 144: 407–414.
Anderson JE, Appelbaum FR, Schoch G, Gooley T, Anasetti C, Bensinger WI et al. Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors. Blood 1996; 87: 51–58.
O'Donnell MR, Long GD, Parker PM, Niland J, Nademanee A, Amylon MD et al. Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelodysplasia. J Clin Oncol 1995; 13: 2973–2979.
Ferrant A, Labopin M, Frassoni F, Prentice HG, Cahn JY, Blaise D et al. Karyotype in acute myeloblastic leukemia: prognostic significance for bone marrow transplantation in first remission: a European Group for Blood and Marrow Transplantation study. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Blood 1997; 90: 2931–2938.
Corradini P, Zallio F, Mariotti J, Farina L, Bregni M, Valagussa P et al. Effect of age and previous autologous transplantation on nonrelapse mortality and survival in patients treated with reduced-intensity conditioning and allografting for advanced hematologic malignancies. J Clin Oncol 2005; 23: 6690–6698.
Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1 H in delaying immune reconstitution. Blood 2002; 99: 4357–4363.
Appelbaum FR, Clift RA, Buckner CD, Stewart P, Storb R, Sullivan KM et al. Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse. Blood 1983; 61: 949–953.
Michallet M, Thomas X, Vernant JP, Kuentz M, Socie G, Esperou-Bourdeau H et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant 2000; 26: 1157–1163.
Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant 2000; 26: 397–404.
Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ . Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5675–5687.
Wendy Ingram is supported by the Leukaemia Research Fund, UK
About this article
Cite this article
Lim, Z., Ingram, W., Brand, R. et al. Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML. Bone Marrow Transplant 45, 633–639 (2010). https://doi.org/10.1038/bmt.2009.236
- reduced-intensity conditioning
Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality
Biology of Blood and Marrow Transplantation (2018)
Prognostic Scoring Systems in Allogeneic Hematopoietic Stem Cell Transplantation: Where Do We Stand?
Biology of Blood and Marrow Transplantation (2017)
Bone Marrow Transplantation (2016)
Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis
Modified EBMT Pretransplant Risk Score Can Identify Favorable-risk Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for AML, Not Identified by the HCT-CI Score
Clinical Lymphoma Myeloma and Leukemia (2015)