Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission

Kyoo-Hyung Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Han-Seung Park, Eun-Ji Choi, Sun-Hye Ko, Miee Seol, Young-Shin Lee, Young-A Kang, Mijin Jeon, Seunghyun Baek, You-Lee Kang, Sung-Han Kim, Sung-Cheol Yun, Hawk Kim, Jae-Cheol Jo, Yunsuk Choi, Young-Don Joo, Sung-Nam Lim, Kyoo-Hyung Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Han-Seung Park, Eun-Ji Choi, Sun-Hye Ko, Miee Seol, Young-Shin Lee, Young-A Kang, Mijin Jeon, Seunghyun Baek, You-Lee Kang, Sung-Han Kim, Sung-Cheol Yun, Hawk Kim, Jae-Cheol Jo, Yunsuk Choi, Young-Don Joo, Sung-Nam Lim

Abstract

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.

Keywords: Acute myeloid leukemia; Allogeneic hematopoietic cell transplantation; Antithymocyte globulin; Busulfan; Fludarabine; HLA-haploidentical family donor; HLA-matched sibling donor; HLA-matched unrelated donor.

Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Source: PubMed

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