Infection-Associated Immune Reconstitution Inflammatory Syndrome in Hematopoietic Cell Transplantation

Immune reconstitution inflammatory syndrome (IRIS) is a well-recognized complication in people with HIV (PWH) starting antiretroviral therapy (ART), but data on IRIS in hematopoietic cell transplantation (HCT) recipients are limited. To address this gap, we conducted a narrative review of the literature on IRIS in HCT recipients, including 21 studies encompassing 53 patients. The majority of reported patients had inborn errors of immunity (IEI) and developed IRIS associated with Bacillus Calmette-Guérin (BCG)-infection from prior vaccination ("BCG-IRIS"). The remainder had IRIS linked to other infections, most commonly Aspergillus and Non-tuberculous mycobacteria ("non-BCG-IRIS"). The median time between transplant and IRIS was 3 months; however, some patients developed IRIS multiple years posttransplant. BCG-IRIS was predominantly unmasking, while non-BCG-IRIS was mostly associated with a new infection acquired after HCT alongside immune recovery and/or changes in immunosuppression ("post-HCT infection IRIS"). Inflammatory biomarkers and tissue pathology were helpful in distinguishing IRIS from uncontrolled infection. Initiation or continuation of appropriate antimicrobial therapy in the peri-transplant period was foremost in the prevention and treatment of IRIS. Use of steroidal and nonsteroidal immunosuppression was common, while surgery was used as an adjunctive measure to infection control. Recrudescence of IRIS symptoms was common with discontinuation or decrease in immunosuppression. About one-third of the patients were reported to have graft-versus-host disease, and the rate of graft failure was 8%. The mortality rate was 15%, with most deaths attributed to superimposed infections. Through this review, we aim to highlight that IRIS is an under-recognized entity in HCT recipients and future research is needed to explore its pathogenesis, risk factors, and management in this complex patient population.