Abstract 9 Hematopoietic Stem Cell Transplantation (HSCT) with Omidubicel Leads to Robust Recovery and Diversity of T Cells

INTRODUCTION: Omidubicel is a cell therapy used for allogeneic hematopoietic stem cell transplant. A phase III randomized study (NCT02730299) comparing omidubicel to umbilical cord blood (UCB) demonstrated faster hematopoietic recovery, lower rates of infection, shorter hospitalization time (Horwitz et al.Blood. 2021;138[16]:1429-1440) and robust immune reconstitution (Szaboles et al. Trans Cell Ther. 2022;28[suppl]:S5). OBJECTIVE: We now characterize T-cell development reflected by T-cell receptor excision circles (TREC) and T-cell receptor (TCR) diversity in omidubicel and UCB-transplanted patients (pts). METHODS: Genomic DNA was extracted from peripheral blood mononuclear cells. TREC was quantified by real-time quantitative PCR. TREC copies (T) were standardized to β actin transcripts (B), and T/B ratio was normalized per µg of DNA. TCR diversity was measured using a total of 76 T-cell receptor β locus (TRB) genes. Human T-cell receptor β repertoire was quantified using AmpliSeq for Illumina Immune Repertoire Plus SR assay. TCRβ metrics quantified the number of clones, Shannon’s entropy, clonality, evenness, convergency, and Gini indexes. RESULTS: A total of 37 pts from 15 sites were included, 17 transplanted with omidubicel and 20 with UCB. Median CD3+ cell dose was lower for pts transplanted with omidubicel (1.8 × 10(6) cells/kg; range: 1.2-7.6) than with UCB (6.0 × 10(6) cells/kg, range: 1.7-10.2). Patients transplanted with omidubicel and UCB had similar TREC and recent thymic emigrants (RTE) counts in peripheral blood at days 100 and 180. At day 365, RTEs were higher in omidubicel (113 ± 85 cells/µL) than UCB (41 ± 15 cells/µL, P = .047). Median T/B ratio was 223 for omidubicel and 124 for UCB. There was no significant difference in TCR repertoire diversity between the omidubicel and UCB groups. DISCUSSION: Pts transplanted with omidubicel had robust and diverse T-cell reconstitution. Higher numbers of de-novo thymus educated T-cells in peripheral blood at 1 year suggest faster thymopoiesis in patients transplanted with omidubicel than with UCB. These data are further evidence for the robust immune reconstitution in patients treated with omidubicel and provide mechanistic rationale for the lower infection rates and improved outcomes in these patients.