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

Authors

Jessica Durkee-Shock, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Children's National Medical Center, Washington, DC.
Anqing Zhang, George Washington University Department of Biostatistics, Washington, DC.
Hua Liang, George Washington University Department of Biostatistics, Washington, DC.
Hannah Wright, USIDNET, Towson, MD.
Julieann Magnusson, USIDNET, Towson, MD.
Elizabeth Garabedian, National Human Genome Research Institute, Bethesda, MD.
Rebecca A. Marsh, Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Kathleen E. Sullivan, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia.
Michael D. Keller, Division of Allergy and Immunology, Children's National Hospital, Washington, DC; Department of Pediatrics, George Washington University, Washington DC. Electronic address: mkeller@childrensnational.org.

Document Type

Journal Article

Publication Date

2-13-2022

Journal

The journal of allergy and clinical immunology. In practice

DOI

10.1016/j.jaip.2022.01.042

Keywords

Combined Immunodeficiency; Hematopoietic Stem Cell Transplantation; Mortality; USIDNET

Abstract

BACKGROUND: Optimal management of patients with combined immunodeficiency (CID), especially pertaining to hematopoietic stem cell transplant (HSCT), remains unclear. OBJECTIVE: Our purpose was to identify factors influencing HSCT and mortality in the CID population in North America. METHODS: We identified 337 participants in the USIDNET database with diverse forms of CID and their characteristics, including demographics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, while 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, while 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; while 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, demographics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality. CONCLUSION: We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. Additionally, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.

APA Citation

Durkee-Shock, Jessica; Zhang, Anqing; Liang, Hua; Wright, Hannah; Magnusson, Julieann; Garabedian, Elizabeth; Marsh, Rebecca A.; Sullivan, Kathleen E.; and Keller, Michael D., "Morbidity, Mortality, and Therapeutics in Combined Immunodeficiency: Data from the USIDNET Registry" (2022). GW Authored Works. Paper 299.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/299

Department

Pediatrics