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Related Collections Clinical Trials and Observations Neoplasia Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3212-3220 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study Alan F. List, Kenneth J. Kopecky, Cheryl L. Willman, David R. Head, Diane L. Persons, Marilyn L. Slovak, Robert Dorr, Chatchada Karanes, Harry E. Hynes, James H. Doroshow, Muhammad Shurafa, and Frederick R. Appelbaum From the Southwest Oncology Group, San Antonio, TX. Cyclosporine A (CsA) inhibits P-glycoprotein (Pgp)-mediated cellular export of anthracyclines at clinically achievable concentrations. This randomized controlled trial was performed to test the benefit of CsA addition to treatment with cytarabine and daunorubicin (DNR) in patients with poor-risk acute myeloid leukemia (AML). A total of 226 patients were randomly assigned to sequential treatment with cytarabine and infusional DNR with or without intravenous CsA. Remitting patients received one course of consolidation chemotherapy that included DNR with or without CsA as assigned during induction. Addition of CsA significantly reduced the frequency of resistance to induction chemotherapy (31% versus 47%, P = .0077). Whereas the rate of complete remission was not significantly improved (39% versus 33%, P = .14), relapse-free survival (34% versus 9% at 2 years, P = .031) and overall survival (22% versus 12%, P = .046) were significantly increased with CsA. The effect of CsA on survival was greatest in patients with moderate or bright Pgp expression (median 12 months with CsA versus 4 months for controls) compared to patients with absent or low Pgp expression (median 6 months in both arms). The frequency of induction deaths was 15% with CsA and 18% in controls. Steady-state serum concentrations of DNR (P = .0089) and daunorubicinol (P < .0001) were significantly higher in CsA-treated patients. Survival (P = .0003) and induction response (P = .028) improved with increasing DNR concentration in CsA-treated patients but not in controls, suggesting a targeted interaction by CsA to enhance anthracycline cytotoxicity. These results indicate that addition of CsA to an induction and consolidation regimen containing infusional DNR significantly reduces resistance to DNR, prolongs the duration of remission, and improves overall survival in patients with poor-risk AML. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Cyclosporine modulation in poor-risk acute myeloid leukemia Jim V. Beattie, Paul J. Petruska, Kenneth J. Kopecky, Alan F. List, and Frederick R. Appelbaum Blood 2002 100: 366-367. [Full Text] [PDF] This article has been cited by other articles: R. M. Stone Genetically Defined Prognostic Factors and Novel Therapeutics for AML ASCO Educational Book, January 1, 2008; 2008(1): 280 - 284. [Abstract] [Full Text] [PDF] S. Chumsri, W. Matsui, and A. M. Burger Therapeutic Implications of Leukemic Stem Cell Pathways Clin. Cancer Res., November 15, 2007; 13(22): 6549 - 6554. 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