Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric cancer patients.

Abstract

1504 Background: Dexrazoxane (DXZ) is an effective cardioprotectant in children with leukemia and solid tumors. However, the potential risk of secondary acute myeloid leukemia (AML) limits DXZ use. We compared the incidence of secondary AML in pediatric cancer patients with and without DXZ exposure to estimate the risk of DXZ-associated secondary AML. Methods: We conducted a retrospective cohort study of anthracycline exposed pediatric cancer patients (excluding de novo AML) hospitalized from January 1999 to March 2011 in 43 freestanding children’s hospitals in the Pediatric Health Information System (PHIS) database. Secondary AML was defined as an ICD9 code for AML that occurred at least 90 days after first anthracycline exposure. Proportions of patients with secondary AML were compared between patients with and without an exposure to DXZ after the initial anthracycline exposure. Results: During the study period of interest, 15,532 pediatric cancer patients were exposed to anthracycline, of which 1404 (9.04%) subsequently received DXZ. Secondary AML was identified in 235 (1.51%) patients. Patients ≥ 10 years of age, black patients, patients in New England and the Midatlantic regions, and those with bone tumors were significantly more likely to have received DXZ. The unadjusted incidence of secondary AML in the DXZ exposed and unexposed patients did not differ significantly (1.21% v. 1.54%, p=0.3308). After adjusting for these variations in demographics, the incidence of secondary AML still did not significantly differ between DXZ exposed and unexposed patients (p=0.6224). Conclusions: Our findings suggest that DXZ exposure does not lead to an increased risk of secondary AML in children. These data are important given the conflicting results from individual clinical trials about the risk of DXZ-associated secondary AML. While subject to well-known limitations of administrative database analyses, these data represent the largest cohort of DXZ exposed patients with available data on the occurrence of secondary AML. Additional multivariate analyses of chemotherapeutic covariates and time to secondary AML are ongoing.