Noriko Mitsuiki, Germany
University of Freiburg Center for Chronic Immunodeficiency, Medical Center of the University HospitalPresenter of 1 Presentation
THE INCREASED RISK OF MALIGNANCIES IN PATIENTS WITH CYTOTOXIC-T-LYMPHOCYTE-ANTIGEN-4 (CTLA-4) INSUFFICIENCY
Abstract
Background and Aims
Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency, caused by heterozygous germline mutations in CTLA4, presents as a complex immune dysregulation syndrome. An increased risk of malignancies in CTLA-4-insufficient patients has been reported in a cohort of the 184 CTLA4 mutation carriers.
Methods
We collected and evaluated clinical information of a worldwide cohort of 203 CTLA4 mutation carriers, which included 144 affected mutation carriers and 59 unaffected mutation carriers. When patients were diagnosed with a malignancy, a malignancy-specific questionnaire was obtained.
Results
We documented 20 malignancies. The incidence of malignancy was 14% in affected CTLA4 mutation carriers. The average age of diagnosis of malignancy was 39 years. The ratio of male to female was eleven to nine. There were eleven hematopoietic malignancies including six Hodgkin lymphomas, four diffuse large B cell lymphomas, one Burkitt lymphoma, one multiple myeloma, and nine solid tumors including five gastric adenocarcinomas, two breast cancers, one squamous cell carcinoma, and one metastatic melanoma. Seven lymphomas and two gastric cancers were EBV-associated. Nine patients, five of which had EBV-associated malignancies, had received immunosuppressive medications when diagnosed with the malignancy. Chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation were undertaken; however, seven patients, five of which had lymphomas, one gastric cancer, and one metastatic melanoma, died.
Conclusions
Half of the malignancies in patients with CTLA-4 insufficiency were lymphomas and EBV-associated. The monitoring of lymphoproliferation and EBV viral load should be carefully performed, especially for affected mutation carriers under immunosuppressive therapy.