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

Abstract

Summary 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.

Can allogeneic haematopoietic cell transplantation be curative in classical Crohn's disease?

“…Admittedly, the patients with IBD described herein differ from classical IBD, in which disease often presents in young adults with complex polygenic susceptibility following exposure to an unknown 'trigger'. In contrast, all of the Moser et al 5 patients developed IBD by the age of 10 years in the setting of an established monogenetic defect known to be cured by allo-HCT in all but one patient (in whom no mutation was identified). However, the use of allo-HCT in patients with classical CD has already been partially explored, primarily in patients with CD who develop a malignancy.…”

“…The remarkably good HCT outcomes described by Moser et al 5 and others, 7 have largely contradicted the notion that patients with IBD fare poorly post‐transplant. Admittedly, the patients with IBD described herein differ from classical IBD, in which disease often presents in young adults with complex polygenic susceptibility following exposure to an unknown ‘trigger’.…”

“…Moser et al 5 describe the success of allogeneic HCT (allo-HCT) in 11 patients with early-onset, very early-onset or infantile IBD arising in the context of a confirmed or presumed monogenetic immune disorder. 5 Historically, allo-HCT has not been pursued in patients with IBD given concerns of toxicity, including a possible increase in severe acute GI graft-versus-host disease (GVHD). In the Moser et al 5 report, severe acute GI GVHD did, in fact develop in a single patient with highly-refractory IBD and continued GI inflammation prior to transplant.…”

“…5 Historically, allo-HCT has not been pursued in patients with IBD given concerns of toxicity, including a possible increase in severe acute GI graft-versus-host disease (GVHD). In the Moser et al 5 report, severe acute GI GVHD did, in fact develop in a single patient with highly-refractory IBD and continued GI inflammation prior to transplant. However, this rate of acute GVHD is lower than what has been reported in large registry studies.…”

Research advancements and perspectives of inflammatory bowel disease: A comprehensive review

“…Eleven pediatric and young adult IBD patients with inborn errors of immunity who received allogeneic hematopoietic stem cell transplantation (alloHSCT) got GI symptom remission. 107 However, monogenic IBD with syntaxin-binding protein 2 mutations is not alleviated by HSCs transplantation. 108 MSCs could promote IBD recovery via modulating gut microbiota and metabolic disorders and upregulating the expression of Mucin 1 to inhibit ferroptosis.…”