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Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report. Blood Adv 2020 Jul 14;4(13):3180-3190

Date

07/15/2020

Pubmed ID

32663298

Pubmed Central ID

PMC7362362

DOI

10.1182/bloodadvances.2019001266

Scopus ID

2-s2.0-85088320644 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

Author List

Zhou Z, Nath R, Cerny J, Wang HL, Zhang MJ, Abdel-Azim H, Agrawal V, Ahmed G, Al-Homsi AS, Aljurf M, Alkhateeb HB, Assal A, Bacher U, Bajel A, Bashir Q, Battiwalla M, Bhatt VR, Byrne M, Cahn JY, Cairo M, Choe H, Copelan E, Cutler C, Damlaj MB, DeFilipp Z, De Lima M, Diaz MA, Farhadfar N, Foran J, Freytes CO, Gerds AT, Gergis U, Grunwald MR, Gul Z, Hamadani M, Hashmi S, Hertzberg M, Hildebrandt GC, Hossain N, Inamoto Y, Isola L, Jain T, Kamble RT, Khan MW, Kharfan-Dabaja MA, Kebriaei P, Kekre N, Khera N, Lazarus HM, Liesveld JL, Litzow M, Liu H, Marks DI, Martino R, Mathews V, Mishra A, Murthy HS, Nagler A, Nakamura R, Nathan S, Nishihori T, Olin R, Olsson RF, Palmisiano N, Patel SS, Patnaik MM, Pawarode A, Perales MA, Politikos I, Popat U, Rizzieri D, Sandmaier BM, Savani BN, Seo S, Shah NN, Uy GL, Valcárcel D, Verdonck LF, Waller EK, Wang Y, Weisdorf D, Wirk B, Wong E, Yared JA, Saber W

Authors

Gulrayz Ahmed MBBS Assistant Professor in the Medicine department at Medical College of Wisconsin
Mehdi Hamadani MBBS Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MBBS, MS Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD, MS Emeritus Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Busulfan
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Melphalan
Transplantation Conditioning