Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

Betül Oran, Kwang Woo Ahn, Caitrin Fretham, Amer Beitinjaneh, Asad Bashey, Attaphol Pawarode, Baldeep Wirk, Bart L. Scott, Bipin N. Savani, Christopher Bredeson, Daniel Weisdorf, David I. Marks, David Rizzieri, Edward Copelan, Gerhard C. Hildebrandt, Gregory A. Hale, Hemant S. Murthy, Hillard M. Lazarus, Jan Cerny, Jane L. LiesveldJean A. Yared, Jean Yves-Cahn, Jeffrey Szer, Leo F. Verdonck, Mahmoud Aljurf, Marjolein van der Poel, Mark Litzow, Matt Kalaycio, Michael R. Grunwald, Miguel Angel Diaz, Mitchell Sabloff, Mohamed A. Kharfan-Dabaja, Navneet S. Majhail, Nosha Farhadfar, Ran Reshef, Richard F. Olsson, Robert Peter Gale, Ryotaro Nakamura, Sachiko Seo, Saurabh Chhabra, Shahrukh Hashmi, Shatha Farhan, Siddhartha Ganguly, Sunita Nathan, Taiga Nishihori, Tania Jain, Vaibhav Agrawal, Ulrike Bacher, Uday Popat, Wael Saber

Research output: Contribution to journalArticlepeer-review


Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.

Original languageEnglish (US)
Pages (from-to)921.e1-921.e10
JournalTransplantation and Cellular Therapy
Issue number11
StatePublished - Nov 2021


  • MDS
  • Melphalan
  • Relapse
  • Survival
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Medicine
  • Hematology
  • Cell Biology
  • Transplantation


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