Tomas Milota, Czech Republic
Second Faculty of Medicine, Charles University and Motol University Hospital Department of ImmunologyPresenter of 1 Presentation
CVID-ASSOCIATED TUMORS: CZECH NATIONWIDE STUDY FOCUSED ON EPIDEMIOLOGY, IMMUNOLOGY AND GENETIC BACKGROUND IN A COHORT OF PATIENTS WITH CVID
Abstract
Background and Aims
Common variable immunodeficiency (CVID) is one of the most frequent primary immunodeficiencies (PIDs) manifesting with increased susceptibility to infections and immune dysregulation. There is also higher risk of malignancies including lymphomas and gastric cancers. Here, we present results of the Czech national multicentric study focused on epidemiology, immunology and genetics in patients with CVID, who developed malignancy.
Methods
A cohort of 295 CVID patients was followed up for 3070 patient-years. SIR (Standardized Incidence Ratio) and RR (Risk Ratio) were calculated to determine the risk of cancer development, to assess predictive value of comorbidities respectively. Furthermore, we performed immunophenotyping of lymphocyte subpopulations and Whole exome sequencing (WES) in all patients with lymphoma.
Results
Twenty-five malignancies were found in 22 CVID patients. The risk for malignancy was 6 times higher in CVID patients compared to the general population. Lymphomas and gastric cancers were the most common malignancies. Immune thrombocytopenic purpura (ITP) was the significant negative prognostic factor with 3-times higher risk for tumor development. Post-treatment T and B cell lymphopenia associated with worse prognosis was found in the majority of patients in contrast to NK cells, which were not affected. WES revealed CVID and well as tumor susceptibility associated genes such as CTLA4, PIK3CD, PMS2; BRCA1, RABEP1, EP300, KDM5A respectively.
Conclusions
There is significantly higher incidence of malignancies in CVID patients, particularly lymphomas and gastric cancers. The history of ITP was identified as negative prognostic factor. WES confirmed wide genetic heterogeneity including causal and modifying variants of CVID as well as tumor susceptibility associated genes.