{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T21:05:52Z","timestamp":1771880752355,"version":"3.50.1"},"reference-count":131,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":4583,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Pediatr. Oncol."],"published-print":{"date-parts":[[1994,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the past decade, therapy\u2010related acute myeloid leukemia (t\u2010AML) following treatment with regimens that include inhibitors of topoisomerase\u2010II (TOPO\u2010II) has been reported with increasing frequency. These cases of t\u2010AML generally have a shorter latency period than t\u2010AML following alkylator therapy, are associated with chromosomal translocations (especially involving chromosome band 11q23), and usually present as M4 or M5 FAB subtype. Although the epipodophyllotoxins (etoposide and teniposide) have been most often implicated, similar cases of t\u2010AML occur following therapy with other classes of Topo\u2010II inhibitors (e.g., anthracyclines).<\/jats:p><jats:p>There is wide variation in published studies in the estimates of risk of t\u2010AML following epipodophyllotoxin therapy. These varying estimates may reflect a number of factors, including: small sample size leading to large confidence intervals around risk estimates; varying susceptibility of different patient populations; varying schedules of epipodophyllotoxin administration; different cumulative doses of epipodophyllotoxins; and administration of epopodophyllotoxins with additional agents that may alter the leukemogenic effect of the epipodophyllotoxins.<\/jats:p><jats:p>Available data suggest that children with acute lymphocytic leukemia (ALL) treated with high cumulative doses of epipodophyllotoxins using either weekly or twice\u2010weekly schedules of administration have a relatively high risk of developing t\u2010AML (5\u201312% cumulative risk). On the other hand, germ cell patients treated with relatively low cumulative doses of etoposide (usually 1,500\u20132,500 mg\/m<jats:sup>2<\/jats:sup>) appear to have a low risk for developing t\u2010AML. There is inadequate experience at this time with higher cumulative doses of etoposide (e.g., 4,000\u20135,000 mg\/m<jats:sup>2<\/jats:sup> as used for pediatric solid tumors) given on a daily x 5 schedule to allow estimates of risk to be developed for this schedule and cumulative dose.<\/jats:p><jats:p>The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan designed to obtain reliable estimates of the risk of t\u2010AML following epipodophyllotoxin treatment. Twelve Cooperative Group clinical trials that use epipodophyllotoxins at either low (&lt;1,500 mg\/m<jats:sup>2<\/jats:sup>), moderate (1,500\u20133,999 mg\/m<jats:sup>2<\/jats:sup>), or higher cumulative doses (&gt;4,000 mg\/m<jats:sup>2<\/jats:sup>) are being prospectively monitored for cases of t\u2010AML occurring among patients entered onto the trials. \u00a9 1994 Wiley\u2010Liss, Inc.<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#note1\"\/><jats:fn><jats:p>This article is a US Government work and, as such, is in the public domain in the United States of America.<\/jats:p><\/jats:fn>\n<\/jats:p>","DOI":"10.1002\/mpo.2950230205","type":"journal-article","created":{"date-parts":[[2007,2,20]],"date-time":"2007-02-20T19:09:24Z","timestamp":1171998564000},"page":"86-98","source":"Crossref","is-referenced-by-count":137,"title":["Therapy\u2010related acute myeloid leukemia following treatment with epipodophyllotoxins: Estimating the 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