Frailty as a Prognostic Factor in Younger Adult Patients With Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND

Frailty is an established predictor of adverse outcomes among older patients undergoing allogeneic hematopoietic cell transplantation (alloHCT), but its prognostic value in younger patients is unclear.

OBJECTIVE

to evaluate whether the previously validated HCT Frailty Scale (HCT-FS) predicts overall survival (OS) and nonrelapse mortality (NRM) in adult patients <65 years with acute myeloid leukemia (AML) undergoing an alloHCT.

STUDY

DESIGN

We evaluated the HCT Frailty Scale (HCT-FS) in adults <65 years in a single-center retrospective cohort of 213 AML alloHCT recipients between 2014 and 2025 during their initial alloHCT consultation. The HCT-FS comprises: the Clinical Frailty Score, instrumental activities of daily living, a timed-up-and-go test, grip strength, self-rated health, falls within the past 6 months, serum albumin, and C-reactive protein levels. Weighted scores classified patients into fit (≤1), prefrail (1 to 5.5), and frail (≥5.5). Primary endpoints were NRM and OS. A Cox model using cubic splines and an age-by-frailty interaction was used to assess prognostic effects and the restricted mean survival time (RMST) at 2 years.

RESULTS

HCT-FS classified 71 patients as fit (33.3%), 111 prefrail (52.1%), and 31 frail (14.6%); the median age was 53 years. After a median follow-up of 43 months, 1-year OS and NRM were 79.7% and 13.4%. Deaths mainly were due to relapse (44%) and infection (32%). One-year OS and NRM differed across groups: 91.4% and 2.9% for fit, 78.2% and 14.0% for prefrail, and 58.1% and 35.5% for frail (P < .001). Compared with fit patients, frail patients had lower OS (hazard ratio [HR] 1.88 [95% CI 1.36 to 2.62], P < .001) and higher NRM (HR 3.36 [1.97 to 5.73], P < .001). Age-adjusted models showed that the adverse impact of frailty, measured by the HCT-FS, persisted across ages 25 to 60 years, without significant age-by-frailty interaction. The RMST at 2 years was shorter in frail patients than in fit patients across all ages. In a multivariate analysis, HCT-FS remained independently associated with NRM (HR 3.1 [1.09 to 9.35], P = .030) and HCT-CI (HR 2.94 [1.44 to 6.03], P = .003), while OS was independently associated only with HCT-CI (HR 2.62 [1.63 to 4.20], P < .001).

CONCLUSIONS

Among adults under 65 years with AML, HCT-FS identified patients at higher risk of death. These results support routine frailty assessment during pretransplant evaluation. Including frailty assessment may help inform risk stratification, conditioning selection, and future interventional studies.