TCR-Depleted Haploidentical Grafts Are a Safe Alternative to HLA-Matched Unrelated Donor Stem Cell Transplants for Infants with Severe Combined…

Hematopoietic stem cell transplantation and gene therapy are the only curative therapies for severe combined immunodeficiency (SCID). In patients lacking a matched donor, TCR/CD19-depleted haploidentical family donor transplant (TCR-HaploSCT) is a promising strategy. Conditioned transplant in SCID correlates to better myeloid chimerism and reduced immunoglobulin dependency. We studied transplant outcome in SCID infants according to donor type, specifically TCR-HaploSCT, and conditioning, through retrospective cohort analysis of 52 consecutive infants with SCID transplanted between 2013 and 2020. Median age at transplant was 5.1months (range, 0.816.6). Donors were TCR-HaploSCT (n=16, 31.4%), matched family donor (MFD,n=15, 29.4%), matched unrelated donor (MUD,n=9, 17.6%), and matched unrelated cord blood (CB,n=11, 21.6%). Forty-one (80%) received fludarabine/treosulfan-based conditioning, 3 (6%) had alemtuzumab only, and 7 (14%) received unconditioned infusions. For conditioned transplants (n=41), 3-year overall survival was 91% (95% confidence interval, 5299%) for TCR-HaploSCT, 80% (4198%) for MFD, 87% (3698%) for MUD, and 89% (4398%) for CB (p=0.89). Cumulative incidence of grade IIIV acute graft-versus-host disease was 11% (279%) after TCR-HaploSCT, 0 after MFD, 29% (7100%) after MUD, and 11% (279%) after CB (p=0.10). 9/10 patients who received alemtuzumab-only or unconditioned transplants survived. Myeloid chimerism was higher following conditioning (median 47%, range 0100%) versus unconditioned transplant (median 3%, 09%) (p<0.001), as was the proportion of immunoglobulin-free long-term survivors (n=29/36, 81% vsn=4/9, 54%) (p<0.001). TCR-HaploSCT has comparable outcome to MUD and is a promising alternative donor strategy for infants with SCID lacking MFD. This study confirms that conditioned transplant offers better myeloid chimerism and immunoglobulin freedom in long-term survivors.

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TCR-Depleted Haploidentical Grafts Are a Safe Alternative to HLA-Matched Unrelated Donor Stem Cell Transplants for Infants with Severe Combined...