Results of the Cord Blood Transplantation Study (COBLT): Clinical outcomes of 193 unrelated donor umbilical cord blood transplantation in pediatric patients with malignant conditions

The Cord Blood Transplantation Study (COBLT), supported by the National Heart, Lung, and Blood Institute, created 2 unrelated donor cord blood banks with an inventory of approximately 8,000 units (CBUs). Six core and 22 collaborating transplant centers enrolled patients on a phase II clinical trial employing a common preparative regimen (TBI/cyclophosphamide/ATG) and prophylaxis against GvHD (cyclosporine/steroids). Children (n= 193; 61% males, 57% Caucasian, 52% CMV+) with ALL, ANLL, MDS or CML not in relapse or blast crisis, median age 7.8 years were transplanted with≥ 5/6, 4/6, or 3/6 HLA-matched CBUs as defined by intermediate-resolution HLA typing at Class IA and IB and high-resolution typing at DRB1. The primary study end point was 180-day survival. CBUs delivering a median precryopreservation cell dose of 5.5× 107 total nucleated cells (TNC)/kg and 1.5× 105 CD34 cells/kg were selected from COBLT or other banks. The cumulative incidence of neutrophil and platelet engraftment with> 90% donor cells was 73% at a median of 28 days and 52% by 180 days, respectively. The cumulative incidence of grade III and IV acute GvHD was 20%, and that of chronic GvHD was 22%. HLA mismatching at the 5/6, 4/6, or 3/6 level by original lower resolution or retrospective high-resolution DNA typing performed on donor/recipient pairs did not correlate with engraftment, GvHD, or survival. In multivariate analysis, seronegativity for CMV was the only factor that correlated with improved survival. TNC and CD34 dose correlated with engraftment of neutrophils and platelets. The COBLT study represents the first multi-institutional, prospective clinical trial in children with malignancies undergoing UCBT. Survival in patients transplanted with low-resolution 4/6 and 5/6 matched grafts is favorable. Partially HLA-matched unrelated cord blood donors provide access to transplantation therapy for pediatric patients with malignancies lacking a matched living donor.