Journal of Clinical Oncology, Vol 16, 3386-3391, Copyright © 1998 by American Society of Clinical Oncology
Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors
C Kollmannsberger, J Beyer, JP Droz, A Harstrick, JT Hartmann, P Biron, A Flechon, P Schoffski, M Kuczyk, HJ Schmoll, L Kanz and C Bokemeyer
Department of Hematology/Oncology, University of Tuebingen Medical Center, Germany.
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 2 g/m2 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/m2). Minimum patient follow-up was 12 months. Standardized morbidity
ratio (SMR) was 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/m2 (range, 2.4 to
14 g/m2). 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-up (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/m2.
HDCT, including etoposide doses greater than 2 g/m2, is associated with an
acceptably low incidence of s-AML in patients with advanced GCT.
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