Paper Details

ABSTRACT

Introduction: Despite improvements in supportive care practices and incorporation of reduced intensity and non-myeloablative conditioning platforms, treatment-related toxicity remains a significant barrier for older adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Current standard comorbidity indices such as the hematopoietic cell transplant comorbidity index (HCT-CI) or Karnofsky performance status (KPS) may not adequately discriminate risk in our older patients (pts) prior to transplant. Identifying better predictors of vulnerability that are potentially modifiable remains an important unmet need to further expand curative HSCT access safely to the older population. ?Herein, we explored the association between geriatric measures and frailty status with post-HSCT outcomes, with the aim of improving pre-transplant risk stratification in older pts.

Methods: Pts (n=63) underwent prospective comprehensive geriatric assessments (CGA) and frailty assessments within 30 days of HSCT at our center (2/2024-2/2026). CGA included evaluation of seven domains, including functional status, comorbidity, cognition, psychological, nutrition, social support and polypharmacy. Frailty was measured by the Fried Frailty Phenotype criteria (FFP), defined by 5 core elements, which further classified patients into frail (F), pre-frail (PF), and robust (R) groups. Baseline patient, disease, and transplant characteristics were collected. Overall survival (OS) was estimated using Kaplan-Meier methods and evaluated using log-rank tests and Cox proportional hazards regression. Multivariable models included frailty and adjusted for age and HCT-CI. Hospital length of stay (LOS) was compared across frailty groups using the Kruskal-Wallis test.

Results: Pts evaluated had a median age at HSCT of 68 years (range, 60-78), and 65.1% were male. HSCT indication was AML in 41.3%, MDS in 25.4%, MPN in 15.9%, NHL in 11.1% and other diseases in 6.3%. Reduced intensity conditioning (RIC) was used in 76.2%, followed by myeloablative in 12.7%, and non-myeloablative in 11.1%.  Among RIC regimens, fludarabine/melphalan was the most common (76.2%). Donors were matched unrelated in 60.3%, followed by mismatched unrelated in 28.6%, haploidentical in 6.3%, and matched-related in 4.8%. PTCy-based graft-versus-host disease (GVHD) prophylaxis was used in 58.7%. Median HCT-CI score was 3 (range, 0-10) and KPS was 80% (range, 70-100). FFP classified 25 (39.7%) pts as robust, 32 (50.8%) as prefrail, and 6 (9.5%) as frail.

With a median observed follow-up of 10.9 mos (range, 0.3-24)?, median OS for the cohort was not reached. Among those with mortality, 55.6% was due to non-relapse causes (NRM), and 44.4% was due to relapse-related causes (RRM).

In unadjusted analyses, only frailty was significantly associated with OS, with frail patients having a significantly higher hazard of death than robust patients (HR 6.00, 95% CI 1.18–30.4; p=0.031). Age at transplant and HCT-CI were not significantly associated with OS. In multivariable analyses, frailty continued to show the strongest association with OS. Frail patients had a significantly higher hazard of death than robust patients after adjustment for both age and HCT-CI (HR 6.82, 95% CI 1.25–37.2; p=0.026). Compared with robust patients, prefrail patients also had a higher hazard of death, although this was not statistically significant (HR 2.28, 95% CI 0.58–8.97; p=0.238). Age at transplant and HCT-CI ≥3 were not independently associated with OS.

Among the CGA domains assessed, only polypharmacy was associated with inferior OS in this cohort, with pts taking ≥6 medications at time of evaluation having significantly worse OS (p=0.019).

The median LOS for patients who were frail was also significantly longer at 60 (range, 42-98) days compared to 28.5 (range, 15-117) and 28.0 (range, 18-43) days in the PF and R groups, respectively (p<0.001).

Conclusions: In an older cohort ≥ 60 years of age, frail patients had significantly worse overall survival compared to robust patients, even after adjustment for age and HCT-CI. Overall, these preliminary findings suggest that frailty is more strongly associated with OS than chronological age or HCT-CI alone and may provide additional value for improved risk stratification of older adults prior to allogeneic HSCT.