Abstract 4 Excellent Event-Free-Survival and Immunoglobulin Independence for Patients with Severe Combined Immunodeficiency Transplanted with Umbilical Cord Blood Stem Cells

Abstract Introduction An HLA matched related donor (MRD) is the preferred donor source for performing a hematopoietic stem cell transplant (HSCT) in patients with severe combined immunodeficiency (SCID) (Heimall 2017). However, many patients lack an MRD and thus an alternative donor, must be used. In these situations, an umbilical cord blood (UCB) represents a promising stem cell source (Gragert 2014, Martinez 2022). Objectives The primary outcome of interest was one-year event free survival (EFS) and the secondary outcome was time to immunoglobulin therapy independence based on donor source. Methods All patients diagnosed with SCID who underwent HSCT at Texas Children’s Hospital from 2003 to 2021 were included. EFS was defined as survival 365 days post-transplant without additional transplant, stem cell “top-off”, or donor lymphocyte infusion. The date of last immunoglobulin infusion was recorded to track time to immunoglobulin therapy independence. Results A total of 67 patients were included in the cohort. One-year EFS was 74.25% for all patients using the Kaplan-Meier method. When stratified by donor/stem cell source, EFS was 88.94% for UCB, 72.92% for MRD, 60.00% for URD, and 41.67% for haplo. There was statistical significance in EFS between URD UCB and the haploidentical group (p = 0.0006). The median time to IVIG independence was 8.6 months for all patients, 7.3 months for UCB, 23.4 months for URD, 26.6 months for haplo, and 32.5 months for MRD. When stratified by donor/stem cell source, cumulative incidence analysis showed UCB patients achieved Immunoglobulin independence earlier when compared to all other groups (UCB vs haplo p = 0.0335, UCB vs MRD p = 0.0012, UCB vs URD p = 0.0488). Discussion This single-center cohort of 67 patients demonstrates excellent survival for SCID patients undergoing HSCT, confirming prior studies (Pai 2014, Heimall 2017). EFS was highest in patients treated with an UCBT. In our analysis of immune reconstitution, we found that SCID patients transplanted with UCB, had a significantly shorter time to IVIG independence compared to other stem cell donors/sources. Given the high survival of UCB patients and this robust immune reconstitution, UCB may represent the best alternative stem cell source for SCID patients without a MRD option.