{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T23:01:28Z","timestamp":1778713288374,"version":"3.51.4"},"reference-count":64,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80% in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined. The occurrence of t-ML among children who had received granulocyte colony-stimulating factor (G-CSF) following ALL remission induction therapy prompted us to examine this and other putative risk factors for t-ML in 412 children treated on 2 consecutive ALL protocols from 1991 to 1998. All children received etoposide and anthracyclines, 99 of whom received G-CSF; 284 also received cyclophosphamide, 58 of whom also received cranial irradiation. There were 20 children who developed t-ML at a median of 2.3 years (range, 1.0-6.0 years), including 16 cases of acute myeloid leukemia, 3 myelodysplasia, and 1 chronic myeloid leukemia. Stratifying by protocol, the cumulative incidence functions differed (P\u2009=\u2009.017) according to the use of G-CSF and irradiation: 6-year cumulative incidence (standard error) of t-ML of 12.3% (5.3%) among the 44 children who received irradiation without G-CSF, 11.0% (3.5%) among the 85 children who received G-CSF but no irradiation, 7.1% (7.2%) among the 14 children who received irradiation plus G-CSF, and 2.7% (1.3%) among the 269 children who received neither irradiation nor G-CSF. Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P\u2009=\u2009.019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML.<\/jats:p>","DOI":"10.1182\/blood-2002-08-2405","type":"journal-article","created":{"date-parts":[[2003,5,5]],"date-time":"2003-05-05T19:24:00Z","timestamp":1052162640000},"page":"3862-3867","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":120,"title":["Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment"],"prefix":"10.1182","volume":"101","author":[{"given":"Mary V.","family":"Relling","sequence":"first","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Boyett","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier G.","family":"Blanco","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Raimondi","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick G.","family":"Behm","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Sandlund","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaston K.","family":"Rivera","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry E.","family":"Kun","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Evans","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Hon","family":"Pui","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmaceutical Sciences, Biostatistics, Pathology, Hematology-Oncology, and Radiation Oncology, St Jude Children's Research Hospital; and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111701463612800_B1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1200\/JCO.1993.11.2.209","article-title":"Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide.","volume":"11","author":"Winick","year":"1993","journal-title":"J Clin Oncol."},{"key":"2019111701463612800_B2","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1056\/NEJM199112123252402","article-title":"Acute myeloid leukemia in children treated with epipodophyllotoxins for acute 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