Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival.

There is no consensus about the best donor for children with non-malignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We now evaluate the 2-year Overall Survival after Umbilical Cord Blood Transplantation (UCBT) in patients with non-malignant disorders from 2009-2020 enrolled on a prospective clinical trial using either 5/6 or 6/6 umbilical cord blood as cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. 55 children were enrolled, median age 5 mo. (range, 1-111 mo.); PID (45), metabolic (5), HLH (1), and hematologic disorders (4). Twenty-six patients had persistent infections prior to transplant. 19 (34%) were 6/6 matched, 36 (66%) were 5/6 HLA matched. The overall survival (OS) at 2 years was 91% (95% CI:79-96%) with a median follow up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range,5-39 days) and 37 days (range,20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of aGvHD grade II-IV by day 100 was 16% (n=9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients have had correction of their immune or metabolic defect. We conclude that in the absence of a MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with non-malignant disorders. This trial is registered at www.clinicaltrials.gov as NCT00950846.