Conditioning Regimens

400 cGy TBI with fludarabine for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation

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Abstract

Fludarabine and 200 cGy TBI are commonly used for reduced-intensity conditioning preceding allogeneic hematopoietic SCT (HSCT). However, graft rejection and disease relapse are significant causes of treatment failure with this regimen. We modified this regimen by escalating the TBI dose to 400 cGy in 40 patients with hematologic malignancies. Thirty-four patients achieved complete donor T-cell chimerism at a median of 40 days following HSCT. The incidences of grades II–IV and III–IV acute GVHD were 40 and 15%, respectively, whereas that of limited and extensive chronic GVHD were 12 and 20%, respectively. Two patients rejected their grafts and 12 relapsed. The 100-day mortality was 18%, 2-year transplant-related mortality 20% and overall survival was 58% at a median follow-up of 16 months. There were no significant survival differences between patients with lymphoid compared to myeloid malignancies. A dose of 400 cGy TBI administered with fludarabine is well tolerated and further study is needed to determine whether outcomes are superior to those with 200 cGy TBI.

Introduction

Allogeneic hematopoietic SCT (HSCT) using reduced-intensity conditioning (RIC) is effective for many patients who are at high risk of transplant-related mortality (TRM) with myeloablative allogeneic HSCT.1, 2, 3, 4, 5 This approach lowers non-relapse mortality rates post transplant. However, disease relapse remains an important cause of treatment failure, particularly for aggressive malignancies such as acute leukemia. Also, while RIC allogeneic HSCT may avoid many of the organ toxicities associated with myeloablative preparative regimens, the risk for developing GVHD and infection still remain significant.

Fludarabine and 200 cGy TBI is a commonly used preparative regimen for RIC allogeneic HSCT.6, 7 We observed a 14% graft rejection rate and a 43% incidence of disease relapse with this regimen at our institution. We hypothesized that these may be improved with escalation of the TBI dose, which was empirically increased to 400 cGy. This report presents our experience with this regimen and compares outcomes observed to our patients who had received fludarabine and 200 cGy TBI.

Patients and methods

Patient characteristics

From December 2003 through April 2007, 40 patients with hematologic malignancies underwent T-cell replete, RIC allogeneic HSCT with 400 cGy TBI and fludarabine at the Cleveland Clinic (Cleveland, OH, USA). Our analysis compared outcomes with 42 patients who received fludarabine and 200 cGy TBI from January 2000 through November 2003. All patients and donors were treated on RIC allogeneic HSCT protocols that were reviewed and approved by the Cleveland Clinic's Institutional Review Board with signed informed consent obtained from all patients before the transplant procedure.

Patient eligibility criteria included a documented diagnosis of a hematologic malignancy. In addition, they were required to have an HLA-matched related donor or an eight of eight HLA-matched unrelated donor by DNA-based typing (HLA-A, -B, -Cw, -DR) as previously described.8, 9, 10 There was no specific upper age limit. Other eligibility requirements included an ECOG performance status of 0 or 1 and a life expectancy of at least 100 days based on the attending physician's assessment. Patients were required to have a normal serum creatinine, a serum total bilirubin <2 mg/dl and AST <2 times the upper limit of normal. Patients were also required to have a left ventricular ejection fraction of at least 45% and an FEV1 and DLCO of 45% predicted. Patients were excluded from enrollment on an RIC allogeneic HSCT trial if they had central nervous system involvement with their disease, an HIV positive status, pregnancy or a concurrent medical or psychiatric illness that could not be controlled with appropriate therapy.

Treatment

Patients received fludarabine 30 mg/m2/day on days −5, −4 and −3 and then TBI 200 cGy on days −1 and 0 (total dose 400 cGy). The TBI dose was delivered using 6 MV photons prescribed to the midplane umbilicus at a dose rate of 5–10 cGy/min at depth. Although no selective lung blocking was used, thermoluminescent dosimetry was performed on each patient to verify final delivered radiation doses. Of note, the first three patients received the total 400 cGy dose on day −1. Due to delayed nausea in these patients, the protocol was amended and all subsequent patients received fractionated TBI as noted above. The donors received G-CSF 10 mcg/kg s.c. daily for PBSC mobilization. Leukapheresis began on the fifth day of G-CSF administration and continued for 2 or 3 days. The minimum number of PBSCs collected was 2.0 × 106 CD34+ cells per kg.

The GVHD prophylaxis for patients with matched sibling donor transplants consisted of CYA 100 mg twice daily starting day −1 and mycophenolate mofetil 500 mg three times per day starting day +1. Patients who had matched unrelated donor transplants were treated on a different protocol in which they received tacrolimus 0.03 mg/kg/day administered in a divided dose twice daily starting day −1 and mycophenolate mofetil 500 mg three times per day starting day +1. In the absence of GVHD, mycophenolate mofetil was discontinued on day +56, whereas CYA and tacrolimus were tapered beginning at day +100 until discontinuing by day +180. On day +5 itraconazole, amoxicillin and acyclovir were started. CMV monitoring was performed with the Digene hybrid capture DNA quantitative assay (Digene Corp., Gaithersburg, MD, USA). Prophylactic gancyclovir (5 mg/kg/day) was routinely administered until day +100 for those patients who were CMV seropositive or whose donors were CMV seropositive.

T-cell chimerism

Short tandem repeat analysis for T-cell chimerism was performed on peripheral blood samples as previously described.8 Specimens were collected initially on day +28, then every 2 weeks for 3 months, then monthly for 3 months, then every 3 months for 4 times, then every 4 months until 2 years post transplant (or more frequent if clinically indicated), then yearly.

Definitions

T-cell complete donor chimerism (CDC) was defined as achievement of 95% DNA of donor origin in the T-cell-enriched fraction. Mixed chimerism was defined as 1% and <95% DNA of donor origin in the T-cell-enriched fraction. Primary graft rejection was defined as severe pancytopenia with failure to ever achieve any donor-derived hematopoiesis. Secondary graft rejection was defined as the complete loss of donor-derived hematopoiesis after complete or mixed chimerism was achieved.

The GVHD grading was performed according to the standard criteria for acute11 and chronic GVHD.12 Relapse-free survival was defined as the time from the date of transplantation until that of first relapse, death or last follow-up. Overall survival was defined as the interval from the date of transplantation until that of death or last follow-up. TRM included patients dying from causes other than relapsed disease, which included GVHD, organ toxicity, infection, hemorrhage, secondary malignancy and graft rejection. Patients were censored for TRM at the time of relapse.

Statistical analysis

Categorical variables were summarized as frequencies and percentages and were compared between the 200 cGy and 400 cGy TBI groups with the χ2 test. Continuous variables were summarized as the median and range and compared between the TBI groups with the Wilcoxon rank sum test. Time-to-event variables without competing risks were estimated with the Kaplan–Meier method13 and compared using the log-rank test, whereas those variables with competing risks (acute and chronic GVHD, achievement of CDC, CMV, other infections, graft rejection, relapse, TRM, donor lymphocyte infusions and subsequent transplants) were estimated with the cumulative incidence method and compared using the Pepe–Mori test.14

Results

Patient pretransplant characteristics are shown in Table 1. Diagnoses were comparable between the 400 and 200 cGy TBI groups, with AML being the most common myeloid disease and non-Hodgkin's lymphoma (NHL) the most common lymphoid disease for each group. There were no significant differences in other baseline characteristics between the groups.

Table 1 Pretransplant characteristics

Achievement of T-cell CDC was similar between the two TBI groups (Table 2). The median times to achieve T-cell CDC was 57 days (range, 13–374 days) for the 200 cGy TBI patients and 40 days (range, 19–360 days) for the 400 cGy TBI patients (P=0.80). There were no differences between the patients who had achieved CDC and those who did not with regards to median CD34+ cell dose infused (200 cGy group: 6.66 vs 6.82 × 106/kg, respectively, P=0.59; 400 cGy group: 4.92 vs 5.20 × 106/kg, respectively, P=0.75) or median CD3+ cell dose infused (200 cGy group: 3.21 vs 3.81 × 108/kg, respectively, P=0.42; 400 cGy group: 4.11 vs 1.60 × 108/kg, respectively, P=0.13). The median times to achieve T-cell CDC for patients with lymphoid vs myeloid diseases were 41 (range, 13–286 days) vs 77 days (range, 19–374 days) in the 200 cGy TBI group (P=0.26) and 30 (range, 19–251 days) vs 61 days (range, 26–360 days) in the 400 cGy TBI group (P=0.29), respectively.

Table 2 Transplant and post transplant characteristics

The 200 cGy TBI group received a higher median CD34+ cell dose than those who received 400 cGy TBI (Table 2). However, there were no differences between the TBI dose groups in severity or incidence of acute or chronic GVHD, time to platelet and neutrophil engraftment, CMV reactivation/infection, other infections or non-infectious toxicities.

Although fewer 400 cGy TBI patients experienced graft rejection than that observed for the 200 cGy TBI group, this did not reach statistical significance (Table 2). The two 400 cGy TBI patients included one with AML who had primary graft rejection and died 2 months post transplant with relapsed disease and one with mantle cell lymphoma who had primary graft rejection and died at 2 months post transplant. The six 200 cGy TBI patients all had secondary graft rejection. These included two AML patients whose graft rejection occurred on days +55 and +125 post transplant in the setting of relapsed disease; a CLL patient who had initially achieved T-cell CDC but then developed graft rejection on day +135 in the setting of disease relapse and gancyclovir-resistant CMV viremia; and three chronic phase CML patients whose graft rejection occurred at 61, 129 and 140 days post transplant. There were no differences between the patients who had graft rejection and those who did not with regards to median CD34+ cell dose infused (200 cGy group: 6.43 vs 6.77 × 106/kg, respectively, P=0.96; 400 cGy group: 4.60 vs 4.94 × 106/kg, respectively, P=0.78) or median CD3+ cell dose infused (200 cGy group: 3.50 vs 3.23 × 108/kg, respectively, P=0.99; 400 cGy group: 1.48 vs 3.72 × 108/kg, respectively, P=0.11).

Response and survival data for specific diagnoses and TBI dose groups are shown in Table 3. Among the patients who received 400 cGy, there were 12 (30%) with disease relapse/progression. Seventeen (42%) deaths occurred, the majority being due to disease relapse (eight patients) followed by acute GVHD (two patients). Thirty patients in the 200 cGy TBI group died, the majority due to disease relapse (10 patients) followed by acute GVHD (6 patients) and chronic GVHD (6 patients). At current follow-up, there are no significant differences in overall and relapse-free survival between the 200 and 400 cGy groups. The TRM at 2 years for the two groups was 26 vs 20% (P=0.77), respectively. However, in the 200 cGy group, patients with lymphoid diseases had superior overall survivals compared to those with myeloid diseases (P=0.047; Figure 1). This difference was no longer observed upon escalating to 400 cGy TBI. Lymphoid malignancy patients treated with 200 cGy TBI also tended to have better relapse-free survival than those with myeloid diseases (P=0.07). In the 400 cGy TBI groups, no differences in relapse-free survival were observed between patients with lymphoid or myeloid diseases. Among those patients with myeloid malignancies the 2-year TRM was 42 vs 19% for the 200 and 400 cGy TBI groups, respectively (P=0.45). For patients with lymphoid malignancies the 2-year TRM was 13 vs 20%, respectively (P=0.71).

Table 3 Responses and survival for the different diagnoses and TBI dose groups
Figure 1
figure1

Kaplan–Meier curves for overall survival on the basis of TBI dose and disease category.

There were no significant differences between related and unrelated donors with regards to relapse-free survival, overall survival and TRM for the 200 cGy or the 400 cGy TBI groups. Graft rejection occurred in 4 (17%) of the 24 who had unrelated donors and 4 (7%) of 69 who had related donor transplants (P=0.25).

Six patients in the 400 cGy TBI group (two NHL, one Hodgkin lymphoma, two multiple myeloma, one myelodysplastic syndrome after a prior autologous HSCT for NHL) had received autologous HSCTs at a median of 24 months (range, 10–78 months) before RIC allogeneic HSCT. Five remain alive at a median of 24 months (range, 5–37 months) post transplant. Only one with Hodgkin lymphoma had a disease relapse and one NHL patient had a stable partial response. One multiple myeloma patient died from relapsed disease at 8 months post transplant. Eleven patients in the 200 cGy TBI group (four NHL, five multiple myeloma, two myelodysplastic syndrome after prior autologous HSCT for NHL and Hodgkin lymphoma) had prior autologous HSCTs at a median of 19 months (range, 3–47 months) before RIC allogeneic HSCT. Three remain alive at 45, 49 and 60 months after RIC allogeneic HSCT. For those who died, the causes of death included three disease relapses, two chronic GVHD, one pulmonary embolism, one pneumonia and one central nervous system hemorrhage at a median of 14 months (range, 4–40 months) post transplant.

In comparison to the patients who received 400 cGy TBI, those in the 200 cGy TBI group more often received second transplants after RIC allogeneic HSCT and more often tended to receive donor lymphocyte infusions post transplant (Table 2).

Discussion

Reduced-intensity conditioning has allowed allogeneic HSCT to be used for many patients who would otherwise not be candidates for transplantation due to older age or comorbidities.1, 2, 3, 4, 5, 15, 16, 17 The ideal regimen would provide sufficient immunosuppression to permit engraftment of donor hematopoietic stem cells, adequate intensity for disease cytoreduction and limited toxicity to normal host tissues. Differences in the intensity of such conditioning may also be appropriate depending on the specific diagnosis being treated and the disease status. More indolent diseases such as CLL and certain lymphomas7, 15 may be managed with less intense regimens, whereas more aggressive malignancies such as AML may require more intense conditioning.6, 17 However, AML patients receiving nonmyeloablative conditioning with only fludarabine and 200 cGy TBI have been reported to do well if the transplant is performed in first CR.18

Increasing dose intensity has been demonstrated to be important for improving disease control and enhancing establishment of long-term CDC after RIC allogeneic HSCT.19, 20 We escalated the TBI dose from 200 to 400 cGy in combination with fludarabine for RIC allogeneic HSCT. There were less relapses in our 400 cGy TBI group, but longer follow-up is needed to confirm the efficacy of this approach for specific disease subtypes. Although we observed fewer cases of graft rejection in the 400 cGy TBI group, this did not reach statistical significance. Escalated TBI doses have been successfully used for RIC allogeneic HSCT and may further enhance engraftment.21, 22 However, much of this experience has been with myeloid malignancies,21, 23, 24, 25 whereas almost half of our patients treated with 400 cGy TBI had lymphoid diseases. At the current follow-up, however, there have been no significant differences in survival outcomes between our myeloid and lymphoid malignancy patients.

Monitoring donor chimerism after RIC allogeneic HSCT has been used to assess for hematopoietic engraftment as well as to determine whether residual disease persists. Achievement of T-cell CDC post transplant has also been considered important to generate a graft vs malignancy effect.3, 26 We observed that most patients treated with 400 cGy TBI achieved T-cell CDC, but this did not significantly differ from those who received 200 cGy TBI. Factors such as the type of hematologic malignancy, amount of pretransplant therapy, source of hematopoietic stem cells, composition of the hematopoietic graft and whether patients received a related vs unrelated donor have been correlated with the development of CDC after RIC allogeneic HSCT.27, 28, 29 We have also previously reported that killer immunoglobulin-like receptor/ligand matching may influence the achievement of T-cell CDC and the development of graft rejection after RIC allogeneic HSCT.8 Strategies to enhance achievement of T-cell CDC may include increasing pretransplant conditioning intensity further and the use of prophylactic donor lymphocyte infusions.

Our results demonstrate that RIC allogeneic HSCT may also successfully salvage patients with recurrent disease after prior autologous HSCT. In our series with 400 cGy TBI, 83% of these patients remained alive at 2 years and 50% were without evidence of recurrent/progressive disease. These results compare favorably to outcomes of lymphoid malignancy patients from prior reports.30, 31 Escalón et al.32 had also reported that nonmyeloablative allogeneic HSCT is an effective option in lymphoma patients with chemosensitive or stable disease who experience disease recurrence following autologous transplantation.

We conclude that 400 cGy TBI administered with fludarabine for RIC allogeneic HSCT is well tolerated and further follow-up is needed to determine if outcomes are superior to those with 200 cGy TBI. The survival difference between patients with lymphoid and myeloid diseases who received 200 cGy TBI was no longer appreciated upon escalating to 400 cGy TBI. This may be due to more comparable relapse-free survivals between these disease groups when treated with 400 cGy TBI. Although this may potentially be due to better cytoreduction from increasing the TBI dose, patient selection may also have influenced outcomes. Future investigation of strategies to further intensify RIC may be appropriate, particularly for patients with myeloid diseases. In addition, prospective comparative trials will be needed to validate the results observed from phase II trials with RIC allogeneic HSCT and to help better define which RIC regimens are most appropriate for specific disease subtypes.

References

  1. 1

    Niederwieser D, Maris M, Shizuru J, Petersdorf E, Hegenbart U, Sandmaier B et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620–1629.

  2. 2

    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.

  3. 3

    Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.

  4. 4

    Giralt S, Thall PF, Khouri I, Wang X, Braunshweig I, Ippolitti C et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.

  5. 5

    McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier B, Molina A, Maloney D 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.

  6. 6

    Scott BL, Sandmaier BM, Storer B, Marris M, Sorror M, Maloney D 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.

  7. 7

    Maris MB, Sandmaier BM, Storer B, Agura E, Wade J, Maziarz R et al. Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for relapsed or refractory follicular lymphoma. Blood 2005; 106: 329a (abstract no. 1130).

  8. 8

    Sobecks RM, Ball EJ, Askar M, Theil K, Rybicki L, Thomas D et al. Influence of killer immunoglobulin-like receptor/HLA ligand matching on achievement of T-cell complete donor chimerism in related donor nonmyeloablative allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41: 709–714.

  9. 9

    Paul P, Apgar J, Ball EJ . HLA-DRB1* intron-primed sequencing for haploid genotyping. Clin Chem 2003; 49: 692–694.

  10. 10

    Paul P, Thomas D, Kawczak P, Good D, Cook DJ, Ball EJ . Resolution of cis-trans ambiguities between HLA-DRB1 alleles using single-strand conformation polymorphisms and sequencing. Tissue Antigens 2001; 57: 300–307.

  11. 11

    Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

  12. 12

    Vogelsang GB . How I treat chronic graft-versus-host disease. Blood 2001; 97: 1196–1201.

  13. 13

    Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1957; 53: 457–481.

  14. 14

    Pepe MS, Mori M . Kaplan–Meier, marginal or conditional probability curves in summarizing competing risk failure data. Stat Med 1993; 12: 737–751.

  15. 15

    Khouri IF, Keating M, Korbling M, Przepiorka D, Anderini P, O’Brien S et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817–2824.

  16. 16

    Chakraverty R, Peggs K, Chopra R, Milligan D, 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.

  17. 17

    Taussig D, Davies A, Cavenagh J, Oakervee H, Syndercombe-Court D, Kelsey S et al. Durable remissions of myelodysplastic syndrome and acute myeloid leukemia after reduced-intensity allografting. J Clin Oncol 2003; 21: 3060–3065.

  18. 18

    Hegenbart U, Niederwieser D, Sandmaier BM, Maris MB, Shizuru JA, Greinix H et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol 2006; 24: 444–453.

  19. 19

    de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 865–872.

  20. 20

    Champlin R, Khouri I, Saliba R, Cohen A, de Lima M, Giralt S . Dose matters: Improved disease control with increased cytoreduction in nonablative BMT for late chronic and accelerated phase CML. Blood 2001; 98: 478a (abstract no. 1996).

  21. 21

    Hallemeier C, Girgis M, Blum W, Brown R, Khoury H, Devine S et al. Long-term remissions in patients with myelodysplastic syndrome and secondary acute myelogenous leukemia undergoing allogeneic transplantation following a reduced intensity conditioning regimen of 550 cGy total body irradiation and cyclophosphamide. Biol Blood Marrow Transplant. 2006; 12: 749–757.

  22. 22

    Kahl C, Mielcarek M, Iwata M, Harkey M, Storer B, Torok-Storb B . Radiation dose determines the degree of myeloid engraftment after nonmyeloablative stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 826–833.

  23. 23

    Weisser M, Schleuning M, Ledderose G, Rolf B, Schnittger S, Schoch C et al. Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant 2004; 34: 1083–1088.

  24. 24

    Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland M, Heinecke A et al. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood 2005; 106: 3314–3321.

  25. 25

    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.

  26. 26

    Antin J, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings. Biol Blood Marrow Transplant 2001; 7: 473–485.

  27. 27

    Baron F, Baker J, Storb R, Gooley TA, Sandmaier BM, Maris MB et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004; 104: 2254–2262.

  28. 28

    Carvallo C, Geller N, Kurlander R, Srinivasan R, Mena O, Igarashi T et al. Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in solid tumor patients. Blood 2004; 103: 1560–1563.

  29. 29

    Valcarcel D, Martino R, Caballero D, Mateos MV, Pérez-Simón JA, Canals C et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 2003; 31: 387–392.

  30. 30

    Fung H, Cohen S, Rodriguez R, Smith D, Krishnan A, Somlo G et al. Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed. Biol Blood Marrow Transplant 2003; 9: 649–656.

  31. 31

    Baron F, Storb R, Storer B, Maris M, Niederwieser D, Shizuru J et al. Factors associated with outcomes in allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning after failed myeloablative hematopoietic cell transplantation. J Clin Oncol 2006; 24: 4150–4157.

  32. 32

    Escalón MP, Champlin RE, Saliba RM, Acholonu SA, Hosing C, Fayad L et al. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol 2004; 22: 2419–2423.

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Sobecks, R., Dean, R., Rybicki, L. et al. 400 cGy TBI with fludarabine for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 42, 715–722 (2008) doi:10.1038/bmt.2008.248

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Keywords

  • 400 cGy TBI
  • reduced-intensity conditioning allogeneic HSCT
  • hematologic malignancy

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