Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
Zheng Zhou, Rajneesh Nath, Jan Černý, 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 S. Cairo, Hannah Choe, Edward A. Copelan, Corey Cutler, Moussab Damlaj, Zachariah DeFilipp, Marcos de Lima, Miguel Ángel Díaz, Nosha Farhadfar, James M. Foran, César O. Freytes, Aaron T. Gerds, Usama Gergis, Michael R. Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh K. Hashmi, Mark Hertzberg, Gerhard Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T. Kamble, Muhammad Khan, Mohamed A. Kharfan‐Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M. Lazarus, Jane L. Liesveld, Mark R. Litzow, Hongtao Liu, David I. Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S. Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca L. Olin, Richard F. Olsson, Neil Palmisiano, Sagar S. Patel, Mrinal M. Patnaik, Attaphol Pawarode, Miguel‐Angel Perales, Ioannis Politikos, Uday Popat, David A. Rizzieri, Brenda M. Sandmaier, Bipin N. Savani, Sachiko Seo, Nirav N. Shah, Geoffrey L. Uy, David Valcárcel, Leo F. Verdonck, Edmund K. Waller, Youjin Wang, Daniel J. Weisdorf, Baldeep Wirk, Eric Wong, Jean A. Yared, Wael Saber
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.