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Outcome of Non-hematological Autoimmunity After Hematopoietic Cell Transplantation in Children with Primary Immunodeficiency

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Abstract

Purpose

Knowledge of post-hematopoietic cell transplantation (HCT) non-hematological autoimmune disease (AD) is far from satisfactory.

Method

This multicenter retrospective study focuses on incidence, risk factors, and outcomes of post-HCT AD in 596 children with primary immunodeficiency (PID) who were transplanted from 2009 to 2018.

Results

The indications of HCT were severe combined immunodeficiency (SCID, n = 158, 27%) and non-SCID PID (n = 438, 73%). The median age at HCT was 2.3 years (range, 0.04 to 18.3 years). The 5-year overall survival for the entire cohort was 79% (95% cumulative incidence (CIN), 74–83%). The median follow-up of surviving patients was 4.3 years (0.08 to 14.7 years). The CIN of post-HCT AD was 3% (2–5%) at 1 year post-HCT, 7% (5–11%) at 5 years post-HCT, and 11% (7–17%) at 8 years post-HCT. The median onset of post-HCT AD was 2.2 years (0.12 to 9.6 years). Autoimmune thyroid disorder (n = 19, 62%) was the most common post-HCT AD, followed by neuromuscular disorders (n = 7, 22%) and rheumatological manifestations (n = 5, 16%). All patients but one required treatment for post-HCT AD. After multivariate analysis, age at transplant (p = 0.01) and T cell–depleted graft (p < 0.001) were significant predictors of post-HCT AD. None of the T cell–depleted graft recipients developed post-HCT AD. Patients with a lower CD3+ count at 6 months post-HCT had a significant higher incidence of post-HCT AD compared to disease controls. Graft-versus-host disease, viral infection, and donor chimerism had no association with post-HCT AD.

Conclusion

Post-HCT AD occurred in 11% at 8 years post-HCT and its occurrence was associated with older age at HCT and unmanipulated graft.

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Acknowledgments

We would like to thank all patients, their families, and the treating multidisciplinary team.

Author information

Author notes

  1. Arjan Lankester and Mary Slatter contributed equally to the senior authorship.

Authors and Affiliations

  1. Children’s Haematopoietic Stem Cell Transplant Unit, Great North Children’s Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Clinical Resource Building, Floor 4, Block 2, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK

    Su Han Lum, Inigo Perez-Heras, Zohreh Nademi, Terry Flood, Sophie Hambleton, Andrew R. Gennery & Mary Slatter

  2. Willem-Alexander Children’s Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

    Su Han Lum, Federica R. Achini, Robbert G. M. Bredius & Arjan Lankester

  3. Department of Immunology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Reem Elfeky, Bianca Cinicola, Austen Worth & Waseem Qasim

  4. Division of Pediatric Stem Cell Transplantation and Children’s Research Center (CRC), University Children’s Hospital of Zurich, Zurich, Switzerland

    Federica R. Achini

  5. Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Adriana Margarit-Soler, Kanchan Rao, Robert Chiesa, Persis Amrolia & Paul Veys

  6. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Zohreh Nademi, Tim Cheetham, Mario Abinun, Sophie Hambleton, Andrew R. Gennery & Mary Slatter

  7. Department of Paediatric Endocrinology, Great North Children’s Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK

    Tim Cheetham

  8. Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Rakesh Amin

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  1. Su Han Lum
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Contributions

SHL developed the concept of the research, collected the data, performed the statistical analysis, interpreted the data, and prepared the manuscript. MS and AL contributed equally to the conceptualization of the research, statistical analysis, and interpretation of the data, manuscript writing, and critical review at every level of the research stages. RE, FRA, AMS, BC, IPH, and NR collected the data and reviewed the manuscript. ZN, TF, TC, AW, WQ, RA, KR, RC, RGMB, PA, MA, SH, PV, and AG critically reviewed the manuscript.

Corresponding author

Correspondence to Su Han Lum.

Ethics declarations

Written informed consent was obtained from the patients and/or parents or legal guardians of the patients as per institutional practice for HCT.

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The authors declare that they have no competing interests.

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Lum, S.H., Elfeky, R., Achini, F.R. et al. Outcome of Non-hematological Autoimmunity After Hematopoietic Cell Transplantation in Children with Primary Immunodeficiency. J Clin Immunol 41, 171–184 (2021). https://doi.org/10.1007/s10875-020-00895-3

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