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Older patients with myelodysplastic syndromes (MDS) preparing to undergo hematopoietic stem cell transplantation (HSCT) may experience improved survival if they receive reduced-intensity conditioning with fludarabine and melphalan compared with fludarabine and busulfan, according to research presented at the 61st American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.
Researchers retrospectively assessed 1065 patients with MDS older than 60 years who had received first HSCT with reduced-intensity conditioning from human leukocyte antigen-matched donors. Fludarabine and busulfan was administered to 597 patients and fludarabine and melphalan was administered to 448 patients. Baseline characteristics were mostly similar between the patient groups.
At 1 year, relapse incidence was 25% with fludarabine and melphalan and 43% with fludarabine and busulfan (P <.001), and this different persisted at 2 and 3 years following HSCT. Conversely, treatment-related mortality was increased in patients receiving fludarabine and melphalan compared with patients receiving fludarabine and busulfan (at 1 year, 26% vs 16%; P <.001).
Nonetheless, fludarabine and melphalan was associated with significantly improved disease-free survival compared with fludarabine and busulfan (47% vs 41%; P =.030) “because the magnitude of improvement in relapse incidence was way higher than the magnitude of increase in treatment-related mortality,” noted presenter Betul Oran, MD, MS, of the University of Texas MD Anderson Cancer Center in Houston. Disease-free survival remained superior with fludarabine and melphalan at 2 and 3 years following HSCT.
Overall survival was similar between the regimens for the first 2 years after HSCT. However, at 3 years following HSCT, fludarabine and melphalan was associated with improved overall survival (P =.19).
Although patients receiving fludarabine and melphalan did not experience increased rates of chronic or severe acute graft-versus-host disease (GVHD), they did experience increased rates of grade 2 to 4 acute GVHD compared with patients receiving fludarabine and busulfan (P =.006). After 2 months, GVHD-free/relapse-free survival was superior in patients receiving fludarabine and melphalan.
“The question came to our minds: Is there any risk group [of patients] that we should recommend fludarabine and busulfan to [in order] to lower transplant-related mortality?” Dr Oran explained. “We had multiple models of multivariable regression analysis, and we consistently observed that fludarabine and melphalan was better for relapse incidence and also improved progression-free survival.”
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Oran B, Ahn KW, Frethan C, et al. Fludarabine and melphalan compared with reduced doses of busulfan and fludarabine improves transplant outcomes in older MDS patients. Oral presentation at: 61st ASH Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 253.