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Lookup NU author(s): Dr Christo TsilifisORCiD, Dr Su Han Lum, Dr Zohreh Nademi, Professor Sophie HambletonORCiD, Dr Terence Flood, Dr Eleri Williams, Dr Stephen Owens, Dr Mario Abinun, Professor Andrew Cant, Professor Mary Slatter, Professor Andrew GenneryORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Hematopoietic stem cell transplantation and gene therapy are the only curative therapies for severe combined immunodeficiency (SCID). In patients lacking a matched donor, TCRαβ/CD19-depleted haploidentical family donor transplant (TCRαβ-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 TCRαβ-HaploSCT, and conditioning, through retrospective cohort analysis of 52 consecutive infants with SCID transplanted between 2013 and 2020. Median age at transplant was 5.1 months (range, 0.8–16.6). Donors were TCRαβ-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, 52–99%) for TCRαβ-HaploSCT, 80% (41–98%) for MFD, 87% (36–98%) for MUD, and 89% (43–98%) for CB (p = 0.89). Cumulative incidence of grade II–IV acute graft-versus-host disease was 11% (2–79%) after TCRαβ-HaploSCT, 0 after MFD, 29% (7–100%) after MUD, and 11% (2–79%) 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 0–100%) versus unconditioned transplant (median 3%, 0–9%) (p < 0.001), as was the proportion of immunoglobulin-free long-term survivors (n = 29/36, 81% vs n = 4/9, 54%) (p < 0.001). TCRαβ-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.
Author(s): Tsilifis C, Lum SH, Nademi Z, Hambleton S, Flood TJ, Williams EJ, Owens S, Abinun M, Cant AJ, Slatter MA, Gennery AR
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Immunology
Year: 2022
Volume: 42
Pages: 851-858
Print publication date: 01/05/2022
Online publication date: 19/03/2022
Acceptance date: 21/02/2022
Date deposited: 21/03/2022
ISSN (print): 0271-9142
ISSN (electronic): 1573-2592
Publisher: Springer
URL: https://doi.org/10.1007/s10875-022-01239-z
DOI: 10.1007/s10875-022-01239-z
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