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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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Autoimmune cytopenias (AIC) are a known complication of hematopoietic stem cell transplant that can lead to increased morbidity and mortality. Higher rates of AIC have been reported in patients transplanted for nonmalignant conditions ranging from 19.5%-56% with the highest rate reported in very young infants (≤3 months) with non-malignant diseases who had undergone unrelated cord blood transplants following ablative conditioning with serotherapy. Evaluate incidence of AIC in non-malignant pediatric patients receiving an umbilical cord blood transplant conditioned with a fully ablative regimen without serotherapy. We performed a retrospective chart review of 42 pediatric patients receiving umbilical cord blood transplants (UCBT) for nonmalignant disease from 2009-2017. Indications included: SCID (30), IPEX (2), LAD (1), WAS (1), CGD (1), metabolic disorders (3), HLH (1), and other hematologic disorders (3). All patients received Busulfan, Cyclophosphamide, and Fludarabine without serotherapy. AIC included: Autoimmune hemolytic anemia, defined as clinically significant hemolysis (a drop in hemoglobin >2 g/dL, reticulocytosis) and positive direct antiglobulin test (DAT); Immune thrombocytopenia purpura, defined as presence of antiplatelet antibodies with new thrombocytopenia; and autoimmune neutropenia, defined as presence of anti-neutrophil antibodies and neutropenia <1000 not responsive to GCSF. All patients engrafted after receiving a cord blood unit with a median TNC of 15 × 107 kg (range, 5.1 – 26.4). The median time to neutrophil and platelet recovery were 18 days (range,6-30d) and 35 days (range,22-85d), respectively. All but one evaluable patient achieved full donor chimerism (defined as > 95% donor cells in peripheral blood by day +42). The overall incidence of AIC was 11.9% (n=5/42). For patients transplanted at age ≤3 months old, only 1 patient developed AIC (n=1/16). AIC included: AIHA (n=2), Evan's syndrome (n=2) and AIHA in combination with autoimmune neutropenia (n=1).There was no evidence of isolated ITP. Of note, one patient with leaky SCID who developed AIHA had a history of AIHA prior to transplant. Average time of onset of AICs post-transplant was 4.6 months (range 3.9-5.4 months). Four of the patients who had AICs had leaky SCID. The remaining patient had IPEX. All patients with AIC received UCB matched at 8 and 9 alleles. Mixed donor chimerism was noted in 3 patients at time of development of AIC. We have observed decreased rates of AIC after UCBT in pediatric patients with nonmalignant diseases, particularly in patients transplanted at ≤ 3 months age, which compared favorably to previous reports. We hypothesize that omission of serotherapy after UCBT allows for early T cell recovery perhaps allowing for expansion of regulatory T cells and decreased rates of autoimmunity. [ABSTRACT FROM AUTHOR]

Introduction There is no consensus about the best donor for children with non-malignant disorders in the absence of a matched related donor (MRD). Objectives Evaluate UCBT as an attractive option for these patients because of prompt availability, lower risk of GvHD, and increased cell dose at young ages. Methods From 2008-2017, we performed UCBT in 42 children, median age 5 mo. (range, 2–108 mo.) with: SCID (30), IPEX (2), LAD (1), WAS (1), CGD (1), metabolic disorders (3), HLH (1), and other hematologic disorders (3). 26 patients had persistent infections prior to transplant: PJP (5), fungal (1), RSV (4), Parainfluenza 3 (4), VZV (1), Norovirus (1), CMV (4), Rhinovirus (2), bacterial (4); with 9 patients having pneumonia (20%), and 7 (17%) patients requiring mechanical ventilation prior to transplantation. Thirty-four percent of patients were 6/6 HLA antigen matched, and 66% were one HLA antigen mismatched. All patients were enrolled on a prospective clinical trial using fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. The median TNC was 15 × 107 kg (range, 5.1 – 26.4). Results The median time to neutrophil and platelet recovery were 18 days (range,6-30d) and 35 days (range,22-85d), respectively. All but one evaluable patient achieved full donor chimerism (defined as > 95% donor cells in peripheral blood by day +42). The overall survival (OS) at 2 years was 90% (95% CI:77-96%) with a median follow up of 4 years (range: 0.5 – 8.5yr). The OS for patients with SCID was 93.3% (28/30) at 2 years with engraftment of all lineages. Four patients died, from severe GvHD (n=2) and MOF (n=2). The cumulative incidence of aGvHD grade II-IV by day 100 was 16% (n=7) with only 2 (IV). No cGvHD has been seen. All but three patients developed engraftment syndrome at a median time of 19 days, (range: 6-46) successfully treated with steroids. All patients with viral infections at the time of transplant cleared infection at a median time of 54 days (range, 44-91). ELISpot analysis after resolution of infections showed T cell responses against the pertinent viruses. The median absolute CD3 (x10^6/L) counts by day 42 and 60 were 361 and 733; respectively. The median absolute CD3CD4 counts by day 42 and 60, were 296, and 506; respectively. The median absolute CD3CD8 absolute count by day 42 and 60, were 71 and 114; respectively. IVIg was discontinued at a median 138 days; (range: 52-769d). Median time to begin immunizations was 11 months, (range: 8-26). All evaluable patients have had correction of their immune or metabolic defect including adequate B cell function in SCID patients. Conclusion We conclude that in the absence of a MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in children with non-malignant disorders, producing rapid engraftment, prompt functional immune-reconstitution, and a low incidence of GvHD. [ABSTRACT FROM AUTHOR]