Malignancy in Ataxia Telangiectasia (A-T)

Abstract

RationaleAtaxia telangiectasia (A-T) is an autosomal recessive DNA repair disorder caused by biallelic mutations in the ATM gene. Clinical features include immunodeficiency, neurodegeneration and cancer predisposition. About 25% of A-T patients will develop early onset malignancies, which are difficult to treat given hypersensitivity to radiation and radiomimetic drugs. Cancer is a leading cause of death in A-T patients. MethodsWe queried the Johns Hopkins A-T Clinical Center database for patients with a confirmed cancer diagnosis. A total of 76 out of 505 patients seen at the clinic from 1995 to the present were identified. Patients were characterized by demographics, age at cancer diagnosis, A-T phenotype (classic versus atypical), ATM mutation, type of malignancy, cancer therapy, therapy modifications, therapy-associated toxicity, and two-year event free survival. ResultsWe found 56 hematologic malignancies with an average cancer diagnosis age of 14.1 years. Among patients < 18 years of age, hematological malignancies were predominant (91%), whereas among patients >18 years old, solid tumors were common (61%). 34 (60.7%) cases were non-Hodgkin lymphoma, 15 (26.7%) leukemias with T cell predominance, and 7 (12.5%) Hodgkin's lymphomas. There were 24 solid tumors in 22 patients, with an average cancer diagnosis age of 25.3 years; 9 (38%) gastrointestinal, 7 (29%) skin, 3 (13%) breast, 2 (8%) thyroid, and 1 each lung, gynecologic and parotid cancer. We found that 76% of our malignancy cohort died of cancer or therapy complications. ConclusionsWe characterized cancers in the world's largest A-T cohort with the future goal of providing improved malignancy screening and developing research protocols for standardized treatment.