Prospective phase 2 trial of high- and intermediate-intensity myeloablative conditioning for cord blood transplantation.

Umbilical cord blood transplantation (UCBT) is an important alternative donor strategy for patients with high-risk hematologic malignancies. While myeloablative conditioning (MAC) is associated with superior disease control following UCBT compared to reduced-intensity conditioning (RIC), its benefits can be offset by non-relapse mortality (NRM). Intermediate-intensity MAC may preserve the anti-leukemic effects of historically high-intensity MAC while reducing NRM. We conducted a prospective phase 2 trial evaluating outcomes of patients undergoing UCBT following either high-intensity or intermediate-intensity MAC. A total of 132 patients were enrolled between 2006 and 2022, with acute leukemia being the predominant indication. The primary endpoint was overall survival (OS), with secondary endpoints including relapse-free survival (RFS), relapse and NRM. For the overall study population at 1 year, OS was 78% (95% CI, 70-85%) and RFS was 72% (95% CI, 64-79%). Outcomes were comparable between conditioning regimens, with encouragingly low NRM observed in patients receiving intermediate-intensity conditioning, including in the pediatric cohort. Among patients with acute leukemia, measurable residual disease (MRD) positivity at transplant was not associated with an increase in relapse, supporting enhanced GVL following UCBT. These findings were particularly notable in patients with AML. These data demonstrate that UCBT following intermediate intensity MAC is a viable strategy that may reduce toxicity while preserving disease control in selected patients. Collectively, these findings support the unique anti-leukemic properties of UCBT and reinforce its role as a highly effective donor platform for high-risk leukemia in children and adults. This trial was registered at ClinicalTrials.gov as NCT00719888.