Results of the cord blood transplantation study (COBLT): Clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with inborn errors of metabolism

The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, evaluated the outcomes of unrelated donor umbilical cord blood transplantation (UCBT) in 32 patients (56% males; 75% Caucasian) with inborn errors of metabolism. A common protocol was used for the preparative regimen (busulfan, cyclophosphamide, ATG) and GvHD prophylaxis (cyclosporine and steroids). Patients with MPS I Hurler’s syndrome (n= 13; 12 reported NEJM 2004:350:1960–9), Hurler-Sheie syndrome (n= 2), Sanfilippo’s syndrome (n= 2), I-cell disease (n= 1), Krabbe’s disease (n= 7), Tay-Sachs disease (n= 2), and adrenoleukodystrophy (n= 5) with a mean age of 1.83 years were transplanted with an HLA 6/6 (n= 3), 5/6 (n= 14), 4/6 (n= 14), or 3/6 (n= 1) matched unit with a median of 8/6 × 107 nucleated cells/kg selected from COBLT banks (80%) or other banks (20%). CBUs were screened for enzyme activity to prevent use of a carrier donor. The cumulative incidence of neutrophil engraftment and grade III/IV acute GvHD were 84% in a median of 26 days and 19%, respectively. The probability of survival at 180 days and 2 years was 84%. Seven patients died, 1 before and 6 after transplantation (1 of GvHD with infection, 3 of graft failure, 2 of organ failure, and 1 of hemolytic anemia). The surviving patients with MPS syndromes, Tay-Sachs disease, and Krabbe’s disease all stabilized and/or gained skills posttransplantation. One of 5 patients with ALD experienced disease progression, whereas all others stabilized and continue to gain developmental skills. Levels of HLA disparity between recipient and donor determined by retrospective high-resolution DNA typing did not influence engraftment, GvHD, or overall survival. The COBLT study represents the first prospective multicenter trial in children with inborn errors of metabolism undergoing UCBT. UCBT provides rapid access to donors and favorably alters the natural history of the disease and should be considered for patients with metabolic diseases who are eligible for transplantation therapy.