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

J Clin Immunol. 2021 Jan;41(1):171-184. doi: 10.1007/s10875-020-00895-3. Epub 2020 Nov 3.

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.

Keywords: Primary immunodeficiency; children; post-transplant autoimmunity.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / epidemiology*
  • Autoimmune Diseases / etiology*
  • Autoimmunity*
  • Child
  • Child, Preschool
  • Disease Management
  • Disease Susceptibility
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immune Reconstitution
  • Incidence
  • Infant
  • Lymphocyte Count
  • Male
  • Primary Immunodeficiency Diseases / complications*
  • Primary Immunodeficiency Diseases / epidemiology*
  • Primary Immunodeficiency Diseases / therapy
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Transplantation Chimera
  • Treatment Outcome