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 e toposide doses greater than 2g/m(2) in patients with metastatic germ c ell tumors (GCT). Patients and Methods: The incidence of s-AML was ret rospectively assessed in patients treated within clinical trials betwe en January 1986 and February 1996 at four university centers, All pati ents 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 mo rbidity ratio (SMR) wets calculated to estimate the risk associated wi th high cumulative etoposide doses, as compared with the general popul ation. 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, whic h 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 1 98). Two cases of secondary myelodysplasia (s-MDS) developed in patien ts with primary mediastinal GCT, Based on the observed four cases of A ML, 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 t he low incidence of AML in the general population, the significantly e levated risk for developing s-AML affects only 1.3% of all patients wh o receive etoposide doses greater than 2 g/m(2). HDCT, including etopo side 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 America n Society of Clinical Oncology.