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Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.

ABSTRACT: Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TBI (relative risk [RR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI.

SUBMITTER: Copelan EA

PROVIDER: S-EPMC4329042 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.

Copelan Edward A EA Avalos Belinda R BR Ahn Kwang Woo KW Zhu Xiaochun X Gale Robert Peter RP Grunwald Michael R MR Hamadani Mehdi M Hamilton Betty K BK Hale Gregory A GA Marks David I DI Waller Edmund K EK Savani Bipin N BN Costa Luciano J LJ Ramanathan Muthalagu M Cahn Jean-Yves JY Khoury H Jean HJ Weisdorf Daniel J DJ Inamoto Yoshihiro Y Kamble Rammurti T RT Schouten Harry C HC Wirk Baldeep B Litzow Mark R MR Aljurf Mahmoud D MD van Besien Koen W KW Ustun Celalettin C Bolwell Brian J BJ Bredeson Christopher N CN Fasan Omotayo O Ghosh Nilanjan N Horowitz Mary M MM Arora Mukta M Szer Jeffrey J Loren Alison W AW Alyea Edwin P EP Cortes Jorge J Maziarz Richard T RT Kalaycio Matt E ME Saber Wael W

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20141217 3

Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hu ...[more]

PMID: 25528388

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Project description:Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n = 36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n = 60: 35 first complete remission [CR], 18 second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14 g/m(2)/day treosulfan i.v. on days -6 to -4, 30 mg/m(2)/day fludarabine i.v. on days -6 to -2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n = 27) or unrelated (n = 69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n = 10) at the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS (41% versus 79%) at 2 years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.

Dataset Information

Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.

Publications

Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.

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