Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation

Br J Haematol. 2023 Mar;200(5):595-607. doi: 10.1111/bjh.18497. Epub 2022 Oct 10.

Abstract

Patients with inborn errors of immunity (IEI) can suffer from treatment-refractory inflammatory bowel disease (IBD) causing failure to thrive and consequences of long-term multiple immunosuppressive treatments. Allogeneic haematopoietic stem cell transplantation (alloHSCT) can serve as a curative treatment option. In this single-centre retrospective cohort study we report on 11 paediatric and young adult IEI patients with IBD and failure to thrive, who had exhausted symptomatic treatment options and received alloHSCT. The cohort included chronic granulomatous disease (CGD), lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency, STAT3 gain-of-function (GOF), Wiskott-Aldrich syndrome (WAS), dedicator of cytokinesis 8 (DOCK8) deficiency and one patient without genetic diagnosis. All patients achieved stable engraftment and immune reconstitution, and gastrointestinal symptoms were resolved after alloHSCT. The overall survival was 11/11 over a median follow-up of 34.7 months. Graft-versus-host disease (GVHD) was limited to grade I-II acute GVHD (n = 5), one case of grade IV acute GVHD and one case of limited chronic GVHD. Since treatment recommendations are limited, this work provides a centre-specific approach to treatment prior to transplant as well as conditioning in IEI patients with severe IBD.

Keywords: Dock 8; IBD; LRBA; STAT 3 GOF; alloHSCT; immune dysregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Failure to Thrive / complications
  • Graft vs Host Disease*
  • Guanine Nucleotide Exchange Factors
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / genetics
  • Inflammatory Bowel Diseases* / therapy
  • Phenotype
  • Retrospective Studies
  • Transplantation Conditioning / adverse effects
  • Treatment Outcome

Substances

  • LRBA protein, human
  • Adaptor Proteins, Signal Transducing
  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors