Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies.

Purpose: Biallelic mutations in ATM cause ataxia-telangiectasia (AT), a rare inherited disease with a high incidence of cancer. Precise estimates of the risk, presentation, and outcomes of cancer in patients with AT need to be addressed in large series.

Patients And Methods: In this large retrospective cohort, 69 patients with cancers (24.5%) were identified among 279 patients with AT. Centralized review was performed on 60% of the lymphomas. Incidence rates were compared with the French population, and risk factors were analyzed.

Results: Eight patients developed acute leukemias (including four T-cell acute lymphoblastic leukemias), 12 developed Hodgkin lymphoma (HL), 38 developed non-Hodgkin lymphoma (NHL), three developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of 8.3, 10.6, 9.7, 24.2, and 31.4 years, respectively (P < .001). The majority of NHLs were aggressive B-cell NHL. Epstein-Barr virus was associated with all of the HLs and 50% of the NHLs. Overall survival was shorter in patients with AT who developed cancer compared with those who did not develop cancer (15 v 24 years, respectively; P < .001). Survival was improved in patients who achieved a major response to treatment (3.46 v 0.87 years for major v minor responses, respectively; P = .011). Immunodeficiency was associated with increased risk of cancer. ATM mutation type was associated with a difference in survival in the entire cohort but not with cancer incidence or cancer survival.

Conclusion: B-cell NHL, HL, and acute lymphoblastic leukemia occur at a high rate and earlier age than carcinomas in AT. T-PLLs are rarer than initially reported. Prognosis is poor, but patients may benefit from treatment with an improved survival.