Faculty Collaboration Database

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes. Transplant Cell Ther 2021 Nov;27(11):921.e1-921.e10

Date

08/18/2021

Pubmed ID

34403791

Pubmed Central ID

PMC9562611

DOI

10.1016/j.jtct.2021.08.007

Scopus ID

2-s2.0-85121157621 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

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. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Author List

Oran B, Ahn KW, Fretham C, Beitinjaneh A, Bashey A, Pawarode A, Wirk B, Scott BL, Savani BN, Bredeson C, Weisdorf D, Marks DI, Rizzieri D, Copelan E, Hildebrandt GC, Hale GA, Murthy HS, Lazarus HM, Cerny J, Liesveld JL, Yared JA, Yves-Cahn J, Szer J, Verdonck LF, Aljurf M, van der Poel M, Litzow M, Kalaycio M, Grunwald MR, Diaz MA, Sabloff M, Kharfan-Dabaja MA, Majhail NS, Farhadfar N, Reshef R, Olsson RF, Gale RP, Nakamura R, Seo S, Chhabra S, Hashmi S, Farhan S, Ganguly S, Nathan S, Nishihori T, Jain T, Agrawal V, Bacher U, Popat U, Saber W

Authors

Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Busulfan
Graft vs Host Disease
Humans
Melphalan
Middle Aged
Myelodysplastic Syndromes
Survival Analysis
Transplantation Conditioning
Vidarabine