Abstract

Background: There is an increased demand for hematopoietic stem cell transplant (HSCT) to treat various diseases including combined immunodeficiencies (CID), with limited worldwide availability. Variables affecting the decision regarding CID patients' prioritization for HSCT are not known. We aimed to determine general, clinical, and immunologic factors associated with the higher risk of early death (≤6 months after diagnosis) in untransplanted CID patients.

Methods: Data collection was done retrospectively from five centers and included general patients' information, and clinical and laboratory variables. Inclusion criteria were untransplanted patients who are either dead or alive with a follow-up period ≥6 months after diagnosis.

Results: Two hundred and thirty-six CID patients were reported by participating centers, of whom 111 were included in the study with a cumulative follow-up period of 278.6 years. Seventy-two patients died with the median age of death of 10.5 months. 35.1% of the patients succumbed within 6 months after the diagnosis. Having a history of Candida infections, sepsis or hepatomegaly was associated with an increased risk of early death. None of the other general or clinical variables was associated with such risk. Bivariate analysis of lymphocyte subsets showed that patients with the following counts: CD3+ < 100, CD4+ < 200, CD8+ < 50, or CD16+ CD56+ <200 cells/μl had increased risk of early death. In adjusted analysis, increased risk of early death was observed among patients with CD3+ count <100 cells/μl.

Conclusion: Combined immunodeficiencies patients with a history of Candida infections, sepsis, hepatomegaly, or severe T-lymphopenia should be given priority for HSCT to avoid early death.

Keywords: combined immunodeficiency; death; epidemiology; hematopoietic stem cell transplant; inborn error of immunity; infections; newborn screening; outcome; survival.