Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only curative treatment for many older adults with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Although utilization of allo-HCT in older adults has grown in recent years, patients aged ≥75 continue to be underrepresented largely due to persistent concerns about frailty, toxicity, and mortality. As reported by the CIBMTR, ≥75 years old recipients represent just 3% of adult allo-HCT performed in 2023. Many published studies in older adults have often utilized non-myeloablative and reduced intensity conditioning regimens, including fludarabine/total body irradiation, fludarabine/melphalan (FluMel) and fludarabine/busulfan combined with varied graft versus host disease (GVHD) prophylaxis approaches. This early report analyzes 8 patients aged ≥75 undergoing allo-HCT with a consistent FluMel 100 mg/m² regimen and post-transplant cyclophosphamide (PT-Cy) based GVHD prophylaxis, showing evidence of safety, tolerability and efficacy in this older age group. 

Methods: A retrospective analysis of our institution's transplant database was performed to identify those patients treated with FluMel100 conditioning and PT-Cy-based GVHD prophylaxis. A total of 8 patients aged ≥75 years underwent allo-HCT between September 2023 and March 2025. The median age at transplant was 76 years (range 75–78). Patient demographics, GVHD incidence, and transplant outcomes were characterized using descriptive statistics. Overall (OS) and relapse-free survival (RFS) were measured from Day 0 of conditioning until death/relapse/last-follow up. Acute GVHD was graded using MAGIC criteria. All patients underwent pre-transplant geriatric assessments using MoCA, Mini-COG, Timed Up and Go (TUG), Sit to Stand (STS), G8 Screening score (G8), and Edmonton Frail Scale.

Results: Eight patients were included: seven with AML (n=7) and one had MDS (n=1), Kanofsky Performance Status range 80-90%, HCT-CI (Comorbidity Index) range 0-7. All patients received peripheral blood stem cell (PBSC) grafts from human leukocyte antigen (HLA) matched unrelated donors (MUD). PT-Cy dose was 80 mg/kg (n= 7) and 50mg/kg (n= 1). All patients engrafted by neutrophils and platelets, with 100% CD33+ cell donor chimerism at 30 days and 100 days, and CD3+ cell donor chimerism at 30 days of 88-100% (median 100%) and 100 days of 95-100% (median 100%). Median inpatient time was 23 days (range 15–30). None required ICU level care and all discharged home with their respective caregivers.

With median follow-up of 422 days (116-756), the OS at +100 and 1 year was 100%, while 1-year RFS was 87.5% (n= 7/8). Acute GVHD occurred in 50% (n= 4/8) of patients, with all cases involving the skin (grade 1: n=3, grade 3: n=1). One patient required re-admission after the initial transplant hospitalization for treatment of relapsed AML. 

Cognitive and fitness assessments (MoCA, Mini-COG, TUG, STS, G8, and Edmonton Frail Scale) demonstrated preserved cognitive and functional status despite advanced age.

Of the cohort, 1/8 (12.5%) experienced relapse – a 75 year old man with AML, who received 10/10 HLA-matched, DPB1 permissive match graft, followed by PT-Cy 80 mg/kg dose for GVHD Prophylaxis.  They underwent re-induction therapy with cladribine, low dose cytarabine and venetoclax, achieving a complete remission, followed by donor leukocyte infusion (DLI).  This patient remains in a sustained remission over 1 year from DLI.  

Summary: Our study analyzed outcomes in patients aged ≥75 years undergoing allo-HCT with FluMel100 conditioning and PT-Cy at doses of 80mg/kg and 50mg/kg for GVHD prophylaxis. Our data showed geriatric patients with preserved cognitive and functional capacity can achieve high overall survival, low relapse rates, and acceptable rates of both severe and non-severe GVHD using this regimen. Our experience supports referrals of fit, older adults with AML and MDS for allogeneic transplantation. Future directions include further stratification of outcomes based on disease risk, comorbidity burden, GRFS (GVHD-free, Relapse-Free Survival), and analysis of chronic GVHD rates and post-transplant functioning and quality of life as this patient cohort matures, to optimize transplantation strategies for older adults undergoing FluMel with PT-Cy. 

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2025
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