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Outcome of Second Allogeneic HSCT for Patients with Inborn Errors of Immunity: Retrospective Study of 20 Years’ Experience

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Abstract

A significant complication of HSCT is graft failure, although few studies focus on this problem in patients with inborn errors of immunity (IE). We explored outcome of second HSCT for IEI by a retrospective, single-centre study between 2002 and 2022. Four hundred ninety-three patients underwent allogeneic HSCT for severe combined immunodeficiency (SCID; n = 113, 22.9%) or non-SCID IEI (n = 380, 77.1%). Thirty patients (6.0%) required second HSCT. Unconditioned infusion or no serotherapy at first HSCT was more common in patients who required second transplant. Median interval between first and second HSCT was 0.97 years (range: 0.19–8.60 years); a different donor was selected for second HSCT in 24/30 (80.0%) patients. Conditioning regimens for second HSCT were predominately treosulfan-based (with thiotepa: n = 18, 60.0%; without, n = 6, 20.0%). Patients received grafts from peripheral blood stem cell (n = 25, 83.3%) or bone marrow (n = 5, 16.7%) with median stem cell dose 9.5 × 106 CD34 + cells/kilogram (range: 1.4–32.3). Median follow-up was 1.92 years (0.22–16.0). Overall survival was 80.8% and event-free survival was 64.7%. Four patients died, two of early-transplant related complications, and two of late sepsis post-second HSCT. Three patients required third HSCT; all are alive with 100% donor chimerism. Cumulative incidence of acute graft-versus-host disease was 28.4%, (all grade I–II). Viral reactivation was seen in 13/30 (43.3%) patients, including HHV6 (n = 6), CMV (n = 4), and adenovirus (n = 2). At latest follow-up, 25/26 surviving patients have donor chimerism ≥ 90% and 16/25 (64.0%) have discontinued immunoglobulin replacement. Second HSCT offers IEI patients with graft failure curative treatment with good overall survival and immunological recovery.

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Data Availability

The data used in this study are not publicly available but may be available from the authors on reasonable request.

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Acknowledgements

We would like to acknowledge Andrew Irving, Data Manager at our centre, for his extensive support with collating the data used in this study.

Funding

CT is supported by the Job Research Foundation.

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    Authors and Affiliations

    1. Children’s Haematopoietic Stem Cell Transplant Unit, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP, UK

      Priti Mehta, Christo Tsilifis, Su Han Lum, Mary A. Slatter, Sophie Hambleton, Stephen Owens, Eleri Williams, Terry Flood, Andrew R. Gennery & Zohreh Nademi

    2. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK

      Christo Tsilifis, Su Han Lum, Mary A. Slatter, Sophie Hambleton, Andrew R. Gennery & Zohreh Nademi

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    1. Priti Mehta
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    Contributions

    CT and PM hold joint first authorship. ZN conceived the study. CT and PM collected patient data, performed statistical analyses, and drafted the manuscript. SL, MAS, SH, SO, EW, TF, ARG and ZN collected data and critically reviewed the manuscript. All authors contributed to the generation of the final version of the manuscript.

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    Correspondence to Christo Tsilifis.

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    Informed consent for participation in retrospective studies was obtained from all individual participants or their parents, in line with institutional policy.

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    Informed consent for participation in retrospective studies was obtained from all individual participants or their parents, in line with institutional policy.

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     Priti Mehta and Christo Tsilifis hold joint first authorship.

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    Mehta, P., Tsilifis, C., Lum, S.H. et al. Outcome of Second Allogeneic HSCT for Patients with Inborn Errors of Immunity: Retrospective Study of 20 Years’ Experience. J Clin Immunol 43, 1812–1826 (2023). https://doi.org/10.1007/s10875-023-01549-w

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