Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
Authors: Zhou Zheng , Nath Rajneesh , Cerny Jan , Wang Hai-Lin , Zhang Mei-Jie , Abdel-Azim Hisham , Agrawal Vaibhav , Ahmed Gulrayz , Al-Homsi A. Samer , Aljurf Mahmoud , Alkhateeb Hassan B. , Assal Amer , Bacher Ulrike , Bajel Ashish , Bashir Qaiser , Battiwalla Minocher , Bhatt Vijaya Raj , Byrne Michael , Cahn Jean-Yves , Cairo Mitchell , Choe Hannah , Copelan Edward , Cutler Corey , Damlaj Moussab B. , DeFilipp Zachariah , De Lima Marcos , Diaz Miguel Angel , Farhadfar Nosha , Foran James , Freytes César O. , Gerds Aaron T. , Gergis Usama , Grunwald Michael R. , Gul Zartash , Hamadani Mehdi , Hashmi Shahrukh , Hertzberg Mark , Hildebrandt Gerhard C. , Hossain Nasheed , Inamoto Yoshihiro , Isola Luis , Jain Tania , Kamble Rammurti T. , Khan Muhammad Waqas , Kharfan-Dabaja Mohamed A. , Kebriaei Partow , Kekre Natasha , Khera Nandita , Lazarus Hillard M. , Liesveld Jane L. , Litzow Mark , Liu Hongtao , Marks David I. , Martino Rodrigo , Mathews Vikram , Mishra Asmita , Murthy Hemant S. , Nagler Arnon , Nakamura Ryotaro , Nathan Sunita , Nishihori Taiga , Olin Rebecca , Olsson Richard F. , Palmisiano Neil , Patel Sagar S. , Patnaik Mrinal M. , Pawarode Attaphol , Perales Miguel-Angel , Politikos Ioannis , Popat Uday , Rizzieri David , Sandmaier Brenda M. , Savani Bipin N. , Seo Sachiko , Shah Nirav N. , Uy Geoffrey L. , Valcárcel David , Verdonck Leo F. , Waller Edmund K. , Wang Youjin , Weisdorf Daniel , Wirk Baldeep , Wong Eric , Yared Jean A. , Saber Wael 
Published: July 2021

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 &lt; .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 &lt; .001). Long-term relapse was lower with FM (HR = 0.65, P &lt; .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.