Risk of subsequent malignancies in survivors of childhood leukemia

Purpose: The diagnosis of childhood leukemia now carries a much improved overall survival. With this knowledge comes concern for late effects of therapy, especially the risk of secondary malignancy. Methods: Patients diagnosed with AML or ALL between the ages of 0 and 18 years who survived at least 5 years after diagnosis were included in analysis. Cumulative incidence of subsequent malignancy at 30 years was calculated. To compare incidence of subsequent malignancies with rates of the US population, standardized incidence ratios (SIRs) were calculated. Results: Four thousand eight hundred six patients were included in the analysis. Median follow-up was 14.5 years (range 5.0-35.9 years). A total of 82 patients developed a second malignancy. The most common second tumor was brain (24 %) followed by thyroid (22 %). Cumulative incidences of secondary malignancy at 30 years for ALL patients and AML patients were 3.9 and 4.3 %, respectively (p = 0.10). Patients were at an increased risk of malignancy compared to the US population (SIR = 3.9, 95 % CI = 3.2-4.8). The SIR for all malignancies for patients diagnosed between 1973 and 1979, 1980 and 1989, and 1990 and 1999 were 2.1 (95 % CI = 1.3-3.4), 4.3 (95 % CI = 3.1-5.9), and 4.4 (95 % CI = 2.7-6.6), respectively. Conclusions: Although incidence of secondary malignancy at 30 years in survivors of childhood leukemia is low, the rate exceeds the expected rate of malignancy for a cohort of this age by nearly 4:1. The development of a subsequent malignancy has significant impact on overall-survival and continued research is needed to assess the long-term risk of subsequent malignancy with modern therapy. Implications for Cancer Survivors: Although survivors of childhood leukemia experience an increased rate of malignancy compared to their peers, the development of a subsequent malignancy is still a rare event. However, continued long-term follow-up is warranted.