Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

To evaluate the long-term effect of allogenic hematopoietic stem cell transplant (HCT) on chronic granulomatous disease (CGD)–associated inflammatory bowel disease (IBD) and assess the impact of IBD on transplant outcomes.

A total of 145 patients with CGD who underwent allogenic HCT at 26 unique Primary Immune Deficiency Treatment Consortium (PIDTC) centers were included in this study.

This was a retrospective study to evaluate clinical characteristics, laboratory findings, treatment and outcomes of patients with CGD who underwent allogenic HCT. CGD status was confirmed by an abnormal dihydrorhodamine assay or nitroblue tetrazolium oxidation test with a history consistent with CGD. IBD diagnosis was made clinically by physicians. Pre- and post-transplant infections, disease activity, outcomes, and survival were assessed.

Approximately 1/3 of the study patients had CGD-associated IBD. Patients with and without IBD were comparable in median age of diagnosis, genetic cause (most commonly CYBB), and oxidative function. Patients with CGD-associated IBD were transplanted later than those without IBD (median age 11 years vs. 5 years, P < .001). Following HCT, neutrophil recovery occurred before day +100 in 89% of patients with IBD and 93% of patients without IBD (P = .476). Median myeloid donor chimerism five years post HCT was 100% in patients with and without IBD. The occurrence of acute upper gastrointestinal, lower gastrointestinal, and chronic GVHD was similar between groups. There was a trend toward increased risk of acute GVHD, grades II–IV, with CGD-associated IBD (hazard ratio 1.98, P = .051). Five-year overall survival was similar for patients with and without IBD (respectively, 80% and 83%, P = .689). Two years following HCT, 100% of surviving patients with IBD had resolution of IBD.

HCT was curative for CGD-associated IBD. In addition, the diagnosis of CGD-associated IBD should not delay HCT as it does not increase risk of mortality.

Patients with CGD are at increased risk for life-threatening bacterial and fungal infections. Additionally, patients with CGD may develop difficult-to-treat autoinflammatory conditions, such as IBD. Although various forms of systemic immunosuppression have been used, there is currently no standardized treatment recommendation for CGD-associated IBD. Allogenic HCT can be curative for CGD but is not always offered. Authors of this study shows that CGD-associated IBD is not a reason to delay treatment with HCT. CGD-associated IBD was cured in all surviving patients with CGD who underwent HCT. Additionally, there was no significant difference in clinical outcomes or survival in patients with or without IBD. HCT should be considered for the treatment of CGD regardless of concomitant IBD.