Excellent Engraftment with Reduced Treatment Related Mortality for Young Pediatric Patients Using Umbilical Cord Blood Transplantation (UCBT) Conditioned without Serotherapy

Abstract

Introduction There is no consensus regarding the best donor for children undergoing stem cell transplantation in the absence of a matched related donor (MRD), especially for patients with nonmalignant diseases. The incidence of infections, GvHD, and graft failure remain major problems. Objectives Evaluate outcome for patients undergoing UCBT conditioned without serotherapy, which is as an attractive option for these patients because of immediate availability, lower incidence of GvHD, and high probability of adequate cell dose for young patients. Methods From 2008-2019, we performed UCBT in 84 children, median age 10 mo. (range, 2–108 mo.) with: ALL (13), AML (15), MDS (5), SCID (36), IPEX (2), LAD (1), WAS (1), CGD (1), metabolic disorders (4), HLH (2), and hematologic disorders (4). Eleven patients (30%) with malignancies had minimal residual disease present before UCBT. Five patients with AML had chloromas present prior to UCBT. 26 patients with immune deficiencies had persistent infections at transplant. All patients were enrolled on prospective clinical trials. Pts with AML/ MDS/ or nonmalignant disorders received busulfan, cyclophosphamide, and fludarabine; pts with ALL received TBI (12Gy), cyclophosphamide, and fludarabine. No patient was treated with serotherapy. All cord blood units were matched 5 or 6/6 HLA antigens at A, B and allele at DR. Results Infused cord blood contained median TNC 15 × 107 kg (range, 5.1 – 26.4). All evaluable patients engrafted by day 42. The median time to neutrophil and platelet recovery were 18 days (range, 6-42d) and 35 days (range,22-85d), respectively. All evaluable patients achieved full donor chimerism (defined as > 95% donor cells in peripheral blood by day +42). The overall survival (OS) at 2 years was 75% with a median follow up of 5 years (range: 0.5 – 11yr). The OS for patients with SCID was 92% (33/36) at 2 years with engraftment of all lineages. The cumulative incidence of aGvHD grade II-IV by day 100 was 9% (n=8) with only 3 patients having grade IV. No pt developed cGvHD. Twenty-one patients died, 13/21, 62% died from disease relapse or disease progression. Treatment related mortality occurred for 7 patients; severe GvHD (n=2) and MOF (n=5). No infection related mortality was seen. Conclusion We conclude that lacking a MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children. Our experience highlights minimal treatment related mortality, rapid engraftment, resolutions of antecedent infections, and a low incidence of GvHD. These results translate in a better quality of life for these young patients.