Morbidity, Mortality, and Therapeutics in Combined Immunodeficiency: Data From the USIDNET Registry

Background Optimal management of patients with combined immunodeficiency, especially pertaining to hematopoietic stem cell transplantation (HSCT), remains unclear. Objective To identify factors influencing HSCT and mortality in the population with combined immunodeficiency in North America. Methods We identified 337 participants in the United States Immunodeficiency Network database with diverse forms of combined immunodeficiency and their characteristics, including demographic characteristics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, whereas multivariate analysis was performed using multiple Cox proportional hazards. Results On univariate analysis, disseminated invasive viral infections and variants in STAT3, GATA2, and, DOCK8 were associated with increased odds of HSCT. Mucocutaneous fungal infections and variants in STAT3 were associated with increased odds of survival, whereas disseminated/invasive fungal infections, disseminated/invasive viral infections, and parasitic infections were associated with decreased odds of survival. On multiple variable Cox proportional hazards analysis, variants in ZAP70, nonspecific bacterial, and disseminated/invasive viral infections were associated with increased hazards of transplantation, whereas variants in multiple genes (RMRP, NEMO, DOCK8, CD40L, and CARD9), disseminated/invasive viral infections, autoimmune disease, and higher absolute lymphocyte count were associated with increased hazards of death. Importantly, demographic characteristics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality. Conclusions We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. In addition, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.