In pursuit of better outcomes for combined immunodeficiency patients: morbidity and mortality in the USIDNET database
Published: February 12, 2022
While evidence-based treatment of severe combined immunodeficiency and common variable immunodeficiency are rapidly evolving, patients with combined immunodeficiency, characterized by decreased but not absent T cell immunity, remain a management puzzle for clinicians. Providers continue to struggle with decisions of which patients should be referred for hematopoietic stem cell transplantation (HSCT), as they attempt to balance early risk and long-term outcomes. To help physicians decide which patients to recommend for HSCT and the ideal timing of definitive therapy, comprehensive analysis of the factors that may impact this decision in patients with combined immunodeficiency is critical.
As was recently published by Durkee-Shock et al. in The Journal of Allergy and Clinical Immunology: In Practice; the largest cohort of combined immunodeficiency patients to date was analyzed for factors associated with morbidity and mortality, especially regarding HSCT. Important patient characteristics assessed included demographics, infectious history, medical comorbidities, genetics, and laboratory values. Prior literature has emphasized case series of a single phenotype or genetic diagnosis; however, this study uniquely included patients from the United States and Canada with a multitude of diverse genetic diagnosis, as well as patients for whom no causal variant had yet been identified. In addition to univariate analysis of factors associated with HSCT or mortality, the authors constructed multiple variable models integrating all assessed covariates for both outcomes.
Dr. Durkee-Shock and colleagues evaluated 337 patients with combined immunodeficiency participating in the USIDNET database across academic centers throughout the United States and Canada. Presence of severe or invasive viral infection was associated both with proceeding to HSCT and with risk of death regardless of transplant status. Patients with certain genetic diagnoses including cartilage hair hypoplasia, NEMO deficiency, DOCK8 deficiency, CD40L deficiency, and CARD9 deficiency had increased hazards of death on multivariate analysis, also regardless of HSCT status. Importantly, basic laboratory values and lymphocyte phenotyping were not associated with either HSCT or mortality except for absolute lymphocyte count being slightly higher in the deceased as compared to the living patients. There was also evidence of increased mortality associated with autoimmunity reflecting previous observations in common variable immunodeficiency. This study provided a novel opportunity to understand the therapies and outcomes of patients without a genetic diagnosis, as these patients have been excluded from most previously published large case series of individual primary immunodeficiencies. Notably, there was no significant difference in mortality rates or HSCT rates in patients with combined immunodeficiency without a genetic diagnosis, suggesting that providers remain willing to treat patients based on their clinical presentation regardless of molecular diagnosis.
This study represents an important step forward in understanding the patient characteristics associated with HSCT and mortality in patients with combined immunodeficiency. Future prospective studies on these factors may further improve guidance and outcomes for patients with combined immunodeficiency.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.