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

Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai Lin Wang, Mei Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A. Samer Al-Homsi, Mahmoud Aljurf, Hassan B. Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean Yves Cahn, Mitchell CairoHannah Choe, Edward Copelan, Corey Cutler, Moussab B. Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, C. Esar O. Freytes, Aaron T. Gerds, Usama Gergis, Michael R. Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C. Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T. Kamble, Muhammad Waqas Khan, Mohamed A. Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M. Lazarus, Jane L. Liesveld, Mark Litzow, Hongtao Liu, David I. Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S. Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F. Olsson, Neil Palmisiano, Sagar S. Patel, Mrinal M. Patnaik, Attaphol Pawarode, Miguel Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M. Sandmaier, Bipin N. Savani, Sachiko Seo, Nirav N. Shah, Geoffrey L. Uy, David Valc A. Arcel, Leo F. Verdonck, Edmund K. Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A. Yared, Wael Saber

Research output: Contribution to journalArticlepeer-review

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] 5 1.82, P , .001), but was marginally superior beyond 3 months (HR 5 0.87, P 5 .05). LFS was better with FM compared with FB (HR 5 0.89, P 5 .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR 5 3.85, P , .001). Long-term relapse was lower with FM (HR 5 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.

Original languageEnglish (US)
Pages (from-to)3180-3190
Number of pages11
JournalBlood Advances
Volume4
Issue number13
DOIs
StatePublished - Jul 14 2020

Bibliographical note

Funding Information:
The CIBMTR is supported primarily by grants from the National Institutes of Health, National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID) via a Public Health Service grant/cooperative agreement (U24CA076518); NHLBI and NCI (U24HL138660); NHLBI (OT3HL147741, R21HL140314, U01HL128568); Health Resources and Services Administration (HHSH250201700006C); Office of Naval Research (N00014-18-1-2888, N00014-17-1-2850); HRSA subaward (prime contract award SC1MC31881-01-00); NHLBI subawards (prime grant awards R01HL131731, R01HL126589); and subawards from NCI (prime grant awards 5P01CA111412, R01CA152108, 1R01CA231141), NHLBI (prime grant awards 5R01HL129472, 1R01HL131731), and National Institute of Allergy and Infectious Diseases (prime grant award 1U01AI126612). The CIBMTR was also supported by commercial funds from Actinium Pharmaceuticals Inc., Adaptive Biotechnologies, Allovir Inc., Amgen Inc., an anonymous donation to the Medical College of Wisconsin, Anthem Inc., Astellas Pharma US, Atara Biotherapeutics Inc., BARDA, Be the Match Foundation, bluebird bio Inc., Boston Children’s Hospital, Bristol Myers Squibb Co., Celgene Corp., Children’s Hospital of Los Angeles, Chimerix Inc., City of Hope Medical Center, CSL Behring, CytoSen Therapeutics Inc., Daiichi Sankyo Co. Ltd., Dana Farber Cancer Institute, Enterprise Science and Computing Inc., Fred Hutchinson Cancer Research Center, Gamida-Cell Ltd., Genzyme, Gilead Sciences Inc., GlaxoSmithKline, HistoGenetics Inc., Immucor, Incyte Corporation, Janssen Biotech Inc., Janssen Pharmaceuticals Inc., Janssen Research & Development LLC, Janssen Scientific Affairs LLC, Japan Hematopoietic Cell Transplantation Data Center, Jazz Pharmaceuticals Inc., Karius Inc., Karyopharm Therapeutics Inc., Kite (a Gilead Company), Kyowa Kirin, Magenta Therapeutics, Mayo Clinic and Foundation Rochester, Medac GmbH, Mediware, Memorial Sloan-Kettering Cancer Center, Merck & Company Inc., Mesoblast, MesoScale Diagnostics Inc., Millennium, the Takeda Oncology Co., Miltenyi Biotec Inc., Mundipharma EDO, National Marrow Donor Program, Novartis Oncology, Novartis Pharmaceuticals Corporation, Omeros Corporation, Oncoimmune Inc., OptumHealth, Orca Biosystems Inc.,

Funding Information:
Authorship Contribution: Z.Z., R.N., J.C., and W.S. conceived and designed the study; CIBMTR and collaborative transplant centers provided study materials and patients; H.-L.W., M.-J.Z., and W.S. collected and assembled data; Z.Z., R.N., J.C., H.-L.W., M.-J.Z., W.S. analyzed and interpreted the data; Z.Z., R.N., J.C., and W.S. wrote the manuscript; and all coauthors are leading physicians at respective transplant centers that made significant contributions to data collection and submission to the CIBMTR, and participated substantively in the writing of this manuscript 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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't

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