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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1315-1324. Prepublished online as a Blood First Edition Paper on October 27, 2005; DOI 10.1182/blood-2004-08-3218. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3218v1 107/4/1315    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 Becton, D. Articles by Weinstein, H. Search for Related Content PubMed PubMed Citation Articles by Becton, D. Articles by Weinstein, H. Related Collections Neoplasia Clinical Trials and Observations Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421 David Becton, Gary V. Dahl, Yaddanapudi Ravindranath, Myron N. Chang, Fred G. Behm, Susana C. Raimondi, David R. Head, Kimo C. Stine, Norman J. Lacayo, Branimir Ivan Sikic, Robert J. Arceci, and Howard Weinstein From the University of Arkansas for Medical Sciences, Little Rock; the Medical Oncology and the Division of Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, CA; the Children's Hospital of Michigan, Detroit; the Children's Oncology Group, Data Center, Gainesville, FL; St Jude Children's Research Hospital, Memphis, TN; Vanderbilt Children's Hospital, Nashville, TN; the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Massachusetts General Hospital, Boston; and the Children's Oncology Group, Arcadia, CA. Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free survival (EFS) and overall survival (OS). Patients were randomized to receive standard-dose DAT (daunorubicin, cytarabine, and thioguanine) or high-dose DAT during induction. To interfere with P-glycoprotein (P-gp)-dependent drug efflux, the second randomization tested the benefit of cyclosporine (CsA) added to consolidation chemotherapy. Of the 282 children randomly assigned to receive standard DAT induction, 248 (87.9%) achieved remission compared to 253 (91%) of the 278 receiving high-dose DAT (P = ns). Children with HLA-identical sibling donors who achieved a complete remission received an allogeneic bone marrow transplant as consolidation. For the 83 patients receiving a matched related donor bone marrow transplantation (BMT), the 3-year disease-free survival (DFS) is 67%. Of the 418 children who achieved remission and went on to consolidation with and without CsA, the DFS was 40.6% and 33.9%, respectively (P = .24). Overexpression of P-gp was infrequent (14%) in this pediatric population. In this study, intensifying induction with high-dose DAT and the addition of CsA to consolidation chemotherapy did not prolong the durations of remission or improve overall survival for children with AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Does modulation of P-glycoprotein have clinical relevance in pediatric acute myeloid leukemia? Christian Michel Zwaan, Monique L. den Boer, Karin M. Kazemier, Karel Hählen, Anne H. Loonen, Dirk Reinhardt, Ursula Creutzig, Gertjan J. L. Kaspers, Rob Pieters, Gary V. Dahl, Yaddanapudi Ravindranath, Robert J. Arceci, and Howard Weinstein Blood 2006 107: 4975-4977. [Full Text] [PDF] This article has been cited by other articles: J. T. Horan, T. A. Alonzo, G. H. Lyman, R. B. Gerbing, B. J. Lange, Y. Ravindranath, D. Becton, F. O. Smith, and W. G. Woods Impact of Disease Risk on Efficacy of Matched Related Bone Marrow Transplantation for Pediatric Acute Myeloid Leukemia: The Children's Oncology Group J. Clin. Oncol., December 10, 2008; 26(35): 5797 - 5801. [Abstract] [Full Text] [PDF] B. J. Lange, F. O. Smith, J. Feusner, D. R. Barnard, P. Dinndorf, S. Feig, N. A. Heerema, C. Arndt, R. J. Arceci, N. Seibel, et al. Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group Blood, February 1, 2008; 111(3): 1044 - 1053. [Abstract] [Full Text] [PDF] M. M. O'Brien, J. W. Taub, M. N. Chang, G. V. Massey, K. C. Stine, S. C. Raimondi, D. Becton, Y. Ravindranath, and G. V. Dahl Cardiomyopathy in Children With Down Syndrome Treated for Acute Myeloid Leukemia: A Report From the Children's Oncology Group Study POG 9421 J. Clin. Oncol., January 20, 2008; 26(3): 414 - 420. [Abstract] [Full Text] [PDF] G. J.L. Kaspers and C. M. Zwaan Pediatric acute myeloid leukemia: towards high-quality cure of all patients Haematologica, November 1, 2007; 92(11): 1519 - 1532. [Abstract] [Full Text] [PDF] P. Brown, E. McIntyre, R. Rau, S. Meshinchi, N. Lacayo, G. Dahl, T. A. Alonzo, M. Chang, R. J. Arceci, and D. Small The incidence and clinical significance of nucleophosmin mutations in childhood AML Blood, August 1, 2007; 110(3): 979 - 985. [Abstract] [Full Text] [PDF] B. I. Sikic Multidrug resistance and stem cells in acute myeloid leukemia. Clin. Cancer Res., June 1, 2006; 12(11): 3231 - 3232. [Full Text] [PDF]

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