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.