An age of 65 years or older for recipients was independently associated with inferior overall survival (OS) and higher non-relapse mortality (NRM) in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) undergoing first unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy)–based graft-vs-host disease (GVHD) prophylaxis, according to data from a retrospective CIBMTR registry analysis presented at the
Findings showed that the 3-year OS rate was 52.1% in patients 65 years of age or older vs 63.4% in those younger than 65 years (log-rank P < .001). In a multivariate Cox regression adjusted for sex, conditioning intensity, disease risk index (DRI), Karnofsky performance status, HSCT-comorbidity index (HSCT-CI), race, graft source, HLA match, and disease status, older recipient age remained independently associated with worse OS (HR, 1.20; 95% CI, 1.02-1.40; P = .029).
The 3-year cumulative incidence of NRM was 22.7% for older patients vs 13.6% for young patients (subdistribution HR [sHR], 1.56; 95% CI, 1.21-2.01; P < .001).
“Inferior survival in older [HSCT] recipients appears to be driven primarily by host-related vulnerability and treatment-related toxicity rather than impaired disease control or increased alloimmune complications,” lead study author Amna Bint I Munir, MD, an internal medicine resident at North Alabama Medical Center in Florence, Alabama, and colleagues wrote in the poster presentation of the data.
The retrospective cohort study drew on the CIBMTR registry and included 2,271 adult patients with AML, ALL, or MDS who underwent first URD allo-HSCT with PTCy-based GVHD prophylaxis between 2017 and 2021.
Patients were stratified into those younger than 65 years (n = 1,422) and those 65 years of age or older (n = 849).
Outcomes of interest were OS, NRM, relapse, acute GVHD (grades II-IV and III-IV), moderate-to-severe chronic GVHD, and GVHD-free, relapse-free survival (GRFS). Investigators used Kaplan-Meier estimates with log-rank tests, Fine-Gray competing-risk regression for NRM, relapse, and GVHD, and multivariate Cox regression for OS and GRFS, with covariates including sex, conditioning, DRI, KPS, HSCT-CI, race, graft source, HLA match, disease status, donor age, and CMV status.
Baseline characteristics showed that older patients more often had MDS (43% vs 22%), received reduced-intensity or nonmyeloablative conditioning (89% vs 43%), had high or very high DRI (35% vs 28%), and received 8/8 HLA-matched URD grafts (80% vs 70%). Fewer patients in the older cohort had a KPS of 90 to 100 (49% vs 56%; all P < .05).
Allo-HSCT is increasingly performed in older adults as reduced-intensity conditioning and PTCy-based prophylaxis have broadened eligibility, and investigators have continued to evaluate supportive strategies aimed at improving transplant outcomes across hematologic malignancies.2
The 3-year cumulative incidence of relapse was 27.4% in patients 65 years of age or older vs 27.1% in younger patients (P = .259; sHR, 0.90; 95% CI, 0.75-1.08; P = .249). Rates of grade II to IV acute GVHD (sHR, 0.98; 95% CI, 0.81-1.17; P = .785), grade III to IV acute GVHD (sHR, 0.91; 95% CI, 0.64-1.30; P = .600), and moderate-to-severe chronic GVHD (sHR, 0.90; 95% CI, 0.68-1.20; P = .467) were comparable between the groups.
GRFS at 3 years was 38.6% in older patients vs 47.6% in younger patients (P < .001), although the difference did not reach statistical significance in the adjusted Cox model (HR, 1.12; 95% CI, 0.98-1.28; P = .108). Beyond older recipient age, independent predictors of worse OS included reduced-intensity conditioning, higher DRI, KPS below 90, and HCT-CI of 3 or greater.
The authors concluded that allo-HCT with PTCy remains a viable option for carefully selected older adults, given the preservation of disease control and GVHD prevention across age groups; however, they noted that age-adapted strategies are needed to reduce NRM and narrow the survival gap in the older population.
Proposed approaches included reduced PTCy dosing and pre-transplant comorbidity optimization. For future research, the investigators called for validation of the findings with longer follow-up beyond 5 years to capture late relapse and chronic GVHD, as well as prospective studies evaluating lower PTCy doses, specifically in patients 65 years of age or older, to determine whether dose reduction can mitigate NRM while preserving GVHD control.
