{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:56:29Z","timestamp":1790373389045,"version":"4.1.0"},"reference-count":99,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,15]],"date-time":"2008-12-15T00:00:00Z","timestamp":1229299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Secondary acute leukemia is a devastating complication in children and adolescents who have been treated for cancer. Secondary acute lymphoblastic leukemia (s\u2010ALL) was rarely reported previously but can be distinguished today from recurrent primary ALL by comparison of immunoglobulin and T\u2010cell receptor rearrangement. Secondary acute myeloid leukemia (s\u2010AML) is much more common, and some cases actually may be second primary cancers. Treatment\u2010related and host\u2010related characteristics and their interactions have been identified as risk factors for s\u2010AML. The most widely recognized treatment\u2010related risk factors are alkylating agents and topoisomerase II inhibitors (epipodophyllotoxins and anthracyclines). The magnitude of the risk associated with these factors depends on several variables, including the administration schedule, concomitant medications, and host factors. A high cumulative dose of alkylating agents is well known to predispose to s\u2010AML. The prevalence of alkylator\u2010associated s\u2010AML has diminished among pediatric oncology patients with the reduction of cumulative alkylator dose and limited use of the more leukemogenic alkylators. The best\u2010documented topoisomerase II inhibitor\u2010associated s\u2010AML is s\u2010AML associated with epipodophyllotoxins. The risk of s\u2010AML in these cases is influenced by the schedule of drug administration and by interaction with other antineoplastic agents but is not consistently found to be related to cumulative dose. The unpredictable risk of s\u2010AML after epipodophyllotoxin therapy may discourage the use of these agents, even in patients at a high risk of disease recurrence, although the benefit of recurrence prevention may outweigh the risk of s\u2010AML. Studies in survivors of adult cancers suggest that, contrary to previous beliefs, the outcome of s\u2010AML is not necessarily worse than that of de novo AML when adjusted for cytogenetic features. More studies are needed to confirm this finding in the pediatric patient population. Cancer 2009. \u00a9 2008 American Cancer Society.<\/jats:p>","DOI":"10.1002\/cncr.23988","type":"journal-article","created":{"date-parts":[[2008,12,16]],"date-time":"2008-12-16T14:53:20Z","timestamp":1229439200000},"page":"23-35","source":"Crossref","is-referenced-by-count":95,"title":["Acute leukemia as a secondary malignancy in children and adolescents: Current findings and issues"],"prefix":"10.1002","volume":"115","author":[{"given":"Nobuko","family":"Hijiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten K.","family":"Ness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul C.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa M.","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,29]]},"reference":[{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.11.1207"},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112123252402"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.1125"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.1126"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200211000-00004"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401660"},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2006.10.006"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02527.x"},{"key":"e_1_2_4_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0312"},{"key":"e_1_2_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(00)00435-6"},{"key":"e_1_2_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209878"},{"key":"e_1_2_4_13_2","first-page":"27","article-title":"Secondary acute promyelocytic leukemia. 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