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. 2020 Jul 14;4(13):3180-3190.
doi: 10.1182/bloodadvances.2019001266.

Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report

Zheng Zhou  1 , Rajneesh Nath  2 , Jan Cerny  3 , Hai-Lin Wang  4 , Mei-Jie Zhang  4   5 , Hisham Abdel-Azim  6 , Vaibhav Agrawal  7 , Gulrayz Ahmed  8 , A Samer Al-Homsi  9 , Mahmoud Aljurf  10 , Hassan B Alkhateeb  11 , Amer Assal  12 , Ulrike Bacher  13 , Ashish Bajel  14 , Qaiser Bashir  15 , Minocher Battiwalla  16 , Vijaya Raj Bhatt  17 , Michael Byrne  18 , Jean-Yves Cahn  19 , Mitchell Cairo  20 , Hannah Choe  21 , Edward Copelan  22 , Corey Cutler  23 , Moussab B Damlaj  24 , Zachariah DeFilipp  25 , Marcos De Lima  26 , Miguel Angel Diaz  27 , Nosha Farhadfar  28 , James Foran  29 , César O Freytes  30 , Aaron T Gerds  31 , Usama Gergis  32 , Michael R Grunwald  22 , Zartash Gul  33 , Mehdi Hamadani  4 , Shahrukh Hashmi  34   35 , Mark Hertzberg  36 , Gerhard C Hildebrandt  37 , Nasheed Hossain  38 , Yoshihiro Inamoto  39 , Luis Isola  40 , Tania Jain  41 , Rammurti T Kamble  42 , Muhammad Waqas Khan  43 , Mohamed A Kharfan-Dabaja  44 , Partow Kebriaei  15 , Natasha Kekre  45 , Nandita Khera  46 , Hillard M Lazarus  47 , Jane L Liesveld  48 , Mark Litzow  49 , Hongtao Liu  50 , David I Marks  51 , Rodrigo Martino  52 , Vikram Mathews  53 , Asmita Mishra  54 , Hemant S Murthy  44 , Arnon Nagler  55   56 , Ryotaro Nakamura  57 , Sunita Nathan  58 , Taiga Nishihori  54 , Rebecca Olin  59 , Richard F Olsson  60   61 , Neil Palmisiano  62 , Sagar S Patel  63 , Mrinal M Patnaik  11 , Attaphol Pawarode  64 , Miguel-Angel Perales  65 , Ioannis Politikos  65 , Uday Popat  15 , David Rizzieri  66 , Brenda M Sandmaier  67 , Bipin N Savani  68 , Sachiko Seo  69 , Nirav N Shah  70 , Geoffrey L Uy  71 , David Valcárcel  72 , Leo F Verdonck  73 , Edmund K Waller  74 , Youjin Wang  75 , Daniel Weisdorf  76 , Baldeep Wirk  77 , Eric Wong  14 , Jean A Yared  78 , Wael Saber  4
Affiliations

Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report

Zheng Zhou et al. Blood Adv. .

Erratum in

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.

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Conflict of interest statement

Conflict-of-interest disclosure: R.N. serves on the advisory boards of, was paid travel fees to the advisory board, and is a consultant for Actinum, Astellas, Daiichi Sankyo. N.N.S. has received honoraria and/or travel support from Incyte, Celgene, and Miltenyi Biotec; serves on scientific advisory boards for Kite, Celgene, and Cellectar; has equity ownership in Geron, Exelexis, Oncosec, and Cell Vault;, and has received institutional research support for clinical trials from BMS and Miltenyi Biotec. D.R. is an advisory board member for AbbVie, Agios, Jazz Novartis, Sanofi, Teva; a consultant advisory board member for AROG, Bayer, Pfizer; a speaker, advisory board member for Celgene and Gilead; and a speaker, advisory board member, consultant, and has received research funding from Stemline. I.P. is a data and safety monitoring board member for ExcellThera; and has received an educational grant from Merck. M.-A.P. is an ad hoc advisory board member for AbbVie, Bellicum, Bristol-Myers Squibb; a member of the scientific advisory board for MolMed and Nex-Immune; is a consultant for Merck; and has received research funding from Incyte (clinical trial) and Kite/Gilead (clinical trial). R.F.O. reports personal fees from AstraZeneca, outside the submitted work. M. Hertzberg receives speaker fees from and is on the advisory boards for Takeda and Roche; is on the advisory board for MSD; and receives speaker fees from Celgene. M.R.G. is a consultant for Agios, AbbVie, Amgen, Cardinal Health, Celgene, Incyte, Merck, Pfizer, Travagene, and Daischi Dankyo; owns stock in Medtronic; and receives research funding from Farma Therapeutics, Amgen, Genetech, Incyte, Janssen, and Novartis. U.G. receives speaker bureau and travel expense reimbursements from Incyte; research support, speaker bureau, and travel expense reimbursements from Jazz; speaker bureau and travel expense reimbursements from Astellas; and speaker bureau and travel expense reimbursements from Merck. A.T.G. receives grant/research support from Incyte, CTI Biopharma, and Sierra Oncology; and is on the advisory boards for PharmEssentia, CTI Biopharma, Promedior, Kartos, and Pfizer. M.D.L. received research grants from Pfizer and Celgene and is on the advisory boards for Kadmon, Pfizer, Incyte, and BMS. J.C. serves on the advisory boards for and receives travel expense reimbursements for Jazz Pharmaceuticals, Dallcal-Sankyo, and Incyte Inc. V.R.B. receives consulting fees from Rigel, Agios, Incyte, Omeros, and Takeda; has a partnership for health analytic research, LLC, and AbbVie; receives research funding (institutional) from Incyte, Jazz, Tolero Pharmaceuticals, Inc, and the National Marrow Donor Program; and receives drug support for a trial from Oncoceutics. A.A. is on the advisory board of Boston Biomedical and Incyte; receives research funding from Incyte; and is a consultant for Alpha Insights. B.M.S. is a consultant for Kiadis, Actinium Pharmaceutical, and Bristol-Meyers Squibb; has received research funding for clinical trials from Bellicum for clinical trials they sponsor; is a consultant for and has received funds from Actinium Pharmaceutical for trials they sponsor; and her spouse has equity in Oncoresponse, Inipharm, Blaze Bioscience, and AbbVie. G.L.U. is a consultant to Jaz, Astellas, and Genentech; and receives research funding from Macrogenics. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Adjusted survival curve comparing FM vs FB RIC on OS (full cohort).
Figure 2.
Figure 2.
FM vs FB on AML transplant outcomes. Adjusted survival: OS (A) and LFS (B). CIF curves: relapse (C) and NRM (D).
Figure 3.
Figure 3.
Early overall mortality (1 – OS) (≤3 months) comparing FM vs FB based on patient-, disease-, and transplant-related characteristics (full cohort).
Figure 4.
Figure 4.
Late overall mortality (1 – OS) (>3 months) comparing FM vs FB based on patient-, disease-, and transplant-related characteristics (full cohort).
See this image and copyright information in PMC

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