Reduced Autoimmune Cytopenias after Cord Blood Transplant in Pediatric Patients with Nonmalignant Disease Conditioned without Serotherapy

Abstract

Introduction 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. Objectives Evaluate incidence of AIC in non-malignant pediatric patients receiving an umbilical cord blood transplant conditioned with a fully ablative regimen without serotherapy. Methods 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 Results 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. Conclusion 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.