{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:14:16Z","timestamp":1790054056222,"version":"4.0.1"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1998,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> 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). <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> 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 (&gt; 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.1998.16.10.3386","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:28:22Z","timestamp":1487917702000},"page":"3386-3391","source":"Crossref","is-referenced-by-count":174,"title":["Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors."],"prefix":"10.1200","volume":"16","author":[{"given":"C","family":"Kollmannsberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Droz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Harstrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J T","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Biron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Fl\u00e9chon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Sch\u00f6ffski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kuczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H J","family":"Schmoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Kanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Bokemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1998.16.10.3386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:32:03Z","timestamp":1653514323000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1998.16.10.3386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10]]},"references-count":0,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1998,10]]}},"alternative-id":["10.1200\/JCO.1998.16.10.3386"],"URL":"https:\/\/doi.org\/10.1200\/jco.1998.16.10.3386","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10]]}}}