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Blood, 1 January 2007, Vol. 109, No. 1, pp. 46-51. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-01-023101. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2006-01-023101v1 109/1/46    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bhatia, S. Articles by Miser, J. S. Search for Related Content PubMed PubMed Citation Articles by Bhatia, S. Articles by Miser, J. S. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children's Oncology Group Smita Bhatia1,, Mark D. Krailo2, Zhengjia Chen3, Laura Burden3, Frederic B. Askin4, Paul S. Dickman5, Holcombe E. Grier6, Michael P. Link7, Paul A. Meyers8, Elizabeth J. Perlman9, Aaron R. Rausen10, Leslie L. Robison11, Teresa J. Vietti12, and James S. Miser1 1 Division of Pediatric Oncology, City of Hope National Medical Center, Duarte, CA; 2 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles; 3 Children's Oncology Group, Arcadia, CA; 4 Department of Pathology, Johns Hopkins Medical Center, Baltimore, MD; 5 Department of Pathology, Phoenix Children's Hospital, AZ; 6 Department and Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Boston, MA; 7 Stanford University School of Medicine, CA; 8 Memorial Sloan-Kettering Cancer Center, New York, NY; 9 Department of Pathology, Johns Hopkins Hospital, Baltimore, MD; 10 Department of Pediatrics, New York University Medical Center, NY; 11 Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis; 12 Division of Pediatric Hematology/Oncology, Washington University Medical Center, St Louis, MO This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Granowetter, R. Womer, M. Devidas, M. Krailo, C. Wang, M. Bernstein, N. Marina, P. Leavey, M. Gebhardt, J. Healey, et al. Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study J. Clin. Oncol., May 20, 2009; 27(15): 2536 - 2541. [Abstract] [Full Text] [PDF] P. C. Nathan, M. L. Greenberg, K. K. Ness, M. M. Hudson, A. C. Mertens, M. C. Mahoney, J. G. Gurney, S. S. Donaldson, W. M. Leisenring, L. L. Robison, et al. Medical Care in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study J. Clin. Oncol., September 20, 2008; 26(27): 4401 - 4409. [Abstract] [Full Text] [PDF]

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