Comparable outcomes in patients aged ≥70 vs. <70 undergoing allogeneic transplantation with fludarabine and melphalan conditioning and post-transplant cyclophosphamide

Abstract

Abstract Background: Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are predominantly diseases of older adults, with median ages at diagnosis of 69–70 years. Allogeneic hematopoietic cell transplant (allo-HCT) is the only curative option, yet remains underused in older adults due to concerns over toxicity, frailty, and mortality (Meyer et al., Haematologica 2025). Fortunately, as complications from AML/MDS therapy and allo-HCT have declined, the population of patients ≥ 65 receiving allo-HCT continues to grow, constituting 29% of patients receiving allo-HCT in 2023 per CIBMTR data. Reduced-intensity conditioning (RIC) regimens, such as fludarabine and melphalan (FluMel), have been developed to optimize transplant outcomes in older adults and those with significant comorbidities. The advent of post-transplant cyclophosphamide (PTCy) has reduced both acute and chronic graft-versus-host disease (GVHD) rates, further enhancing transplant safety (Bolaños-Meade et al., 2023). While FluMel with PTCy is a commonly used regimen, it remains unclear whether FluMel100-based allo-HCT (melphalan dose of 100mg/m2) offers comparable safety and efficacy in patients ≥70 years old relative to younger patients. Methods: In this retrospective single-center study at Oregon Health & Science University, we examined disease response, toxicity, and GVHD outcomes among patients <70 and ≥70 years of age who received FluMel100 with PTCy from March 2022 to March 2025. Evaluated outcomes included: 1-year overall survival (OS), relapse-free survival (RFS), 100-day survival, relapse incidence, transplant-related mortality (per Copeland Criteria), acute GVHD (aGVHD) incidence and severity (per MAGIC Criteria), aGVHD onset timing and organ involvement, engraftment timing, and hospital length of stay. Baseline characteristics were summarized descriptively. Continuous variables were compared using the Mann-Whitney U test, and categorical variables using Fisher's Exact Test. Survival outcomes (OS, RFS, 100-day survival) were analyzed with Kaplan-Meier estimates and compared using log-rank test. aGVHD was graded per MAGIC criteria, and differences in incidence, severity, and onset were assessed. Results: We compared patients <70 (n=34, median age: 65, range: 24-69) vs. ≥70 (n=25, median age: 73, range: 70-78). Most had MDS or AML; only four patients per group had alternative diagnoses, including CLL, ALL, myelofibrosis, NHL, CMML, and myeloid sarcoma. 32/34 patients <70 years old underwent transplantation with Unrelated Donors (URD); 2/34 patients underwent transplant from an HLA matched sibling. All 25 patients ≥70 received URD; donor grafts were collected from peripheral blood via apheresis. All patients received PTCy, tacrolimus and mycophenolate for GVHD prophylaxis. Median follow-up was 416 days in the <70 group vs. 179 days in the ≥70 group. Median OS was not significantly different (p=0.666). 1-year OS was 88.2% (<70) vs. 92.0% (>70) and was not significantly different (p=0.0785). No significant difference in 1-year RFS (76% for both groups, p=0.2029) nor 100-day survival (96.0% for <70, 91.2% for ≥70, p=0.4789) was observed. Rates of acute GVHD (aGVHD) did not significantly differ (p=0.3012), with similar distributions in severity (p=0.3903) and median onset (42 days for <70 vs. 39 days for ≥70, p=0.0774). Skin was the most affected organ across both groups with aGVHD affecting 66.7% in the <70 group and 83.3% in the ≥70 group. Median length of hospital stay was identical (22 days, p=0.7747). Engraftment failure occurred in two <70 (5.9%) and one ≥70 (3.1%) patient. Among engrafted, 1 death (4.2%) from relapse occurred in each group, and 1 <70 patient (4.2%) died from GVHD (0 in ≥70). Conclusions: Our preliminary findings suggest that patients ≥70 years receiving FluMel100 had comparable outcomes to younger patients in terms of survival, GVHD rates, and hospitalization metrics. Therefore, we conclude that allo-HSCT with FluMel100 conditioning is a tolerable and potentially curative option for older patients over the age of 70 with hematologic malignancies. Older adults with hematologic malignancies should be referred for allo-HCT consideration. Future analyses in this population will investigate the impact of comorbidity scores, PTCy dosing, GRFS (GVHD-free, Relapse-Free Survival), functional status, and toxicities including chronic GVHD on patient outcomes.