Competing risks of relapse and major organ failure after allogeneic hematopoietic cell transplantation.

Abstract

e18579 Background: Outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) are often summarized using overall survival (OS) or treatment related mortality (TRM), which may obscure distinct biologic and toxicity driven pathways of failure. Major organ toxicities are important causes of morbidity and mortality but are rarely evaluated as competing events alongside relapse. We sought to characterize relapse and major organ failure as distinct competing pathways after allo-HCT. Methods: We analyzed adult allo-HCT recipients from the CIBMTR RT17-01 publicly available dataset (2008-2016). The primary endpoint was the first post transplant failure pathway, defined as relapse, major organ failure (MOF) requiring dialysis or diagnosed as thrombotic microangiopathy (TMA), veno-occlusive disease (VOD), or idiopathic pneumonia syndrome (IPS), or death without prior relapse or MOF. Competing risk methods estimated cumulative incidence, and cause specific Cox models evaluated associations between conditioning intensity and outcomes, adjusting for clinical and transplant related covariates, with the renal component of the hematopoietic cell transplantation comorbidity index (HCT-CI) removed. Results: The cohort included 13,187 adult recipients with a median age of 58.6 years, of whom 59.3 percent were male. Conditioning intensity was myeloablative (MAC) in 6,134 patients, reduced intensity (RIC) in 4,795, and non myeloablative (NMA) in 2,221. The first failure pathway was relapse in 5,157 patients, MOF in 1,511, and death without relapse or MOF in 2,535. At one year, cumulative incidence was 32.4 percent for relapse, 10.4 percent for MOF, and 13.1 percent for death without either event. IPS and dialysis requiring renal failure were the most frequent MOF events. Compared with MAC, RIC was associated with higher relapse risk (adjusted hazard ratio [aHR] 1.14; 95 percent confidence interval [CI] 1.07-1.23) and lower MOF risk (aHR 0.72; 95 percent CI 0.64-0.82). NMA conditioning showed a further shift toward relapse (aHR 1.42; 95 percent CI 1.30-1.54) with greater reduction in MOF risk (aHR 0.55; 95 percent CI 0.46-0.66). Conclusions: Relapse and MOF represent distinct competing pathways of failure after allo-HCT. Conditioning intensity influences which pathway predominates, with less intensive regimens shifting risk from organ toxicity toward relapse. Pathway based competing risk analyses provide insight beyond traditional survival endpoints and may support more individualized transplant decision making.