Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors

Purpose: High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2g/m(2) in patients with metastatic germ cell tumors (GCT). Patients and Methods: The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers, All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m(2)). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) wets calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. Results: A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m(2) (range, 2.4 to 14 g/m(2)). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-vp (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT, Based on the observed four cases of AML, which are most likely etoposide related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. Conclusion: Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m(2). HDCT, including etoposide doses greater than 2 g/m(2), Is associated with an acceptably low incidence of s AML in patients with advanced GCT. (C) 1998 by American Society of Clinical Oncology.