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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.
Biol Blood Marrow Transplant. 2017 Sep; 23(9):1555-1566.BB

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.

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Authors+Show Affiliations

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea. Electronic address: khlee2@amc.seoul.kr.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Hematology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Section of Infectious Diseases, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Division of Hematology and Cellular Therapy, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of Korea.

Division of Hematology and Cellular Therapy, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of Korea.

Division of Hematology and Cellular Therapy, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of Korea.

Hematology-Oncology, Department of Internal Medicine, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.

Hematology-Oncology, Department of Internal Medicine, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.

Pub Type(s)

Clinical Trial, Phase II

Journal Article

Multicenter Study

Language

eng

PubMed ID

28552421

Clinical Trial Links

Allogeneic HCT Using Uniform Conditioning Regimen Regardless of Donors (MS, MU, or HF) for AML in Remission

Haploidentical NK Cells After Pemetrexed in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

Citation

Lee, Kyoo-Hyung, et al. "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." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 23, no. 9, 2017, pp. 1555-1566.

Lee KH, Lee JH, Lee JH, et al. 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. Biol Blood Marrow Transplant. 2017;23(9):1555-1566.

Lee, K. H., Lee, J. H., Lee, J. H., Kim, D. Y., Park, H. S., Choi, E. J., Ko, S. H., Seol, M., Lee, Y. S., Kang, Y. A., Jeon, M., Baek, S., Kang, Y. L., Kim, S. H., Yun, S. C., Kim, H., Jo, J. C., Choi, Y., Joo, Y. D., & Lim, S. N. (2017). 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. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 23(9), 1555-1566. https://doi.org/10.1016/j.bbmt.2017.05.025

Lee KH, et al. 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. Biol Blood Marrow Transplant. 2017;23(9):1555-1566. PubMed PMID: 28552421.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - 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. AU - Lee,Kyoo-Hyung, AU - Lee,Je-Hwan, AU - Lee,Jung-Hee, AU - Kim,Dae-Young, AU - Park,Han-Seung, AU - Choi,Eun-Ji, AU - Ko,Sun-Hye, AU - Seol,Miee, AU - Lee,Young-Shin, AU - Kang,Young-A, AU - Jeon,Mijin, AU - Baek,Seunghyun, AU - Kang,You-Lee, AU - Kim,Sung-Han, AU - Yun,Sung-Cheol, AU - Kim,Hawk, AU - Jo,Jae-Cheol, AU - Choi,Yunsuk, AU - Joo,Young-Don, AU - Lim,Sung-Nam, Y1 - 2017/05/25/ PY - 2017/03/01/received PY - 2017/05/22/accepted PY - 2017/5/30/pubmed PY - 2018/4/26/medline PY - 2017/5/30/entrez KW - Acute myeloid leukemia KW - Allogeneic hematopoietic cell transplantation KW - Antithymocyte globulin KW - Busulfan KW - Fludarabine KW - HLA-haploidentical family donor KW - HLA-matched sibling donor KW - HLA-matched unrelated donor SP - 1555 EP - 1566 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 23 IS - 9 N2 - 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. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/28552421/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(17)30491-3 DB - PRIME DP - Unbound Medicine ER -