Early Mortality and Conditional Long-Term Survival After Adult Umbilical Cord Blood Transplantation: A 1-Year Landmark Analysis.

BACKGROUND: Umbilical cord blood (UCB) is an established alternative graft source for allogeneic hematopoietic cell transplantation (HCT), but adult use is limited by substantial early morbidity and mortality. Conventional survival estimates from transplantation may obscure prognosis among patients who survive the early high-risk period. OBJECTIVE(S): To characterize early mortality, cause-specific death, and conditional long-term survival among adults undergoing first allogeneic UCB transplantation for malignant hematologic disease. STUDY

DESIGN: We conducted a retrospective cohort study using Center for International Blood and Marrow Transplant Research data. Adults 18 years or older who underwent first allogeneic HCT with UCB for malignant hematologic disease between 1999 and 2024 were included. Overall survival (OS) beyond a prespecified 1-year landmark was estimated using the Kaplan-Meier method. Causes of death were summarized before and after the landmark. Cumulative incidence functions were estimated for death attributed to relapse-related causes, death attributed to non-relapse causes, and death with unknown or unavailable cause. Multivariable Cox regression evaluated predictors of post-landmark OS.

RESULTS: Among 6,869 eligible adults, 3,245 (47.2%) died within the first year after transplantation and 3,624 (52.8%) survived to the 1-year landmark. At 12 months, cumulative incidence was 13.66% (95% CI, 12.88%-14.47%) for relapse-related death and 29.46% (95% CI, 28.34%-30.62%) for non-relapse-cause death. Among 1-year survivors, median follow-up was 84.5 months (IQR, 49.6-122.1), median OS from the landmark was 13.7 years (95% CI, 12.4 years to not reached), and 5-year OS was 66.46% (95% CI, 64.81%-68.15%). During post-landmark follow-up, 1,198 deaths occurred. Relapse or progression was the leading recorded cause of late death. At 5 years after the landmark, cumulative incidence was 17.37% (95% CI, 15.97%-18.88%) for relapse-related death and 16.23% (95% CI, 15.16%-17.39%) for death attributed to non-relapse causes. In multivariable analysis, older age, progressive disease, KPS ≤70, and nonmyeloablative conditioning were associated with worse post-landmark OS, while lymphoma was associated with lower mortality compared with acute leukemia. CONCLUSION(S): Adult UCB transplantation is associated with substantial early mortality concentrated within the first post-transplant year. However, among patients who survive the 1-year landmark, long-term survival is durable, and late mortality is driven primarily by relapse. These findings establish a benchmark for conditional survivorship after adult UCB transplantation and support incorporation of landmark-based risk assessment into donor counseling and survivorship planning.