Disability-Free Survival: A Novel Morbidity Endpoint for Older Adult Allogeneic Hematopoietic Cell Transplantation

Transplant-related morbidity remains a major barrier to broader application of allogeneic hematopoietic cell transplantation (HCT) in older adults. The frequency and importance of physical disabilities early after HCT have not been well-characterized. We sought to characterize the incidence and prognostic impact of physical disability complicating HCT in patients ≥60 years of age. We retrospectively analyzed 699 consecutive patients ≥60 years who underwent HCT at our institution. Physical disability post-HCT was defined as one or more of the following: (1) mobility dependence (requiring a person to assist walking); (2) delirium with loss of instrumental activities of daily living; (3) fall; or (4) intensive care unit admission. Disability-free Survival (DiFS) failure events included any of these disability events or death. The median age was 66 years; 20% were age ≥70 years. Melphalan-based conditioning was used in 85%, and 77% had matched donors. By day 30, 38% developed mobility dependence, 25% experienced delirium, 15% required intensive care unit care, and 5% experienced a fall. Day 30 DiFS was 57.2%, with a disability event preceding every death by day 30. One-year NRM landmarked at day 30 was 31.6% for patients with prior disability, versus 9.8% without (P < .001). In multivariable analysis, disability was independently associated with increased landmark NRM (Hazard Ratio [HR] = 2.70, 95% confidence interval [CI]: 2:03 to 3.60) and worse landmark overall survival (HR = 1.86, CI: 1.49 to 2.33), independent of acute graft-versus-host disease by day 30. Disability frequently complicates HCT in older adults and independently predicts higher NRM risk. Day 30 DiFS is a novel endpoint to quantify HCT morbidity and a potential target for trials to circumvent HCT-related complications.