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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4381-4388. Prepublished online as a Blood First Edition Paper on September 6, 2005; DOI 10.1182/blood-2005-06-2217. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-06-2217v1 106/13/4381    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 Giaccone, L. Articles by Georges, G. E. Search for Related Content PubMed PubMed Citation Articles by Giaccone, L. Articles by Georges, G. E. Related Collections Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation Luisa Giaccone, Jeannine S. McCune, Michael B. Maris, Theodore A. Gooley, Brenda M. Sandmaier, John T. Slattery, Scott Cole, Richard A. Nash, Rainer F. Storb, and George E. Georges From the Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington, Seattle, WA; and University of Turin, Turin, Italy. The immunosuppressive drug mycophenolate mofetil (MMF) is used after nonmyeloablative hematopoietic cell transplantation (HCT); however, limited pharmacodynamic data are available. We evaluated plasma concentrations of mycophenolic acid (MPA), the active metabolite of MMF, and outcomes in 85 patients with hematologic malignancies conditioned with fludarabine and 2 Gy total body irradiation followed by HLA-matched unrelated-donor HCT and postgrafting cyclosporine and MMF. The first 38 patients received MMF 15 mg/kg twice daily; the next 47 patients received MMF 3 times daily. MPA pharmacokinetics were determined on days 7 and 21. Comparing the twice-daily and 3-times-daily MMF groups, the mean total MPA concentration steady state (Css) was 1.9 and 3.1 µg/mL; the unbound Css was 18 and 36 ng/mL, respectively (P < .001). Sixteen patients with a total MPA Css less than 3 µg/mL had low (< 50%) donor T-cell chimerism (P = .03), and 6 patients with MPA Css less than 2.5 µg/mL had graft rejection. An elevated unbound Css was associated with cytomegalovirus reactivation (P = .03). There were no significant associations between MPA pharmacokinetics and acute graft-versus-host disease (GVHD) or relapse. We conclude that increased MPA Css's predicted higher degrees of donor T-cell chimerism after unrelated donor nonmyeloablative HCT and suggest that targeting MPA Css's greater than 2.5 µg/mL could prevent graft rejection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Jacobson, J. Huang, N. Rydholm, M. Tran, T. DeFor, J. Tolar, and P. J. Orchard Higher Mycophenolate Dose Requirements in Children Undergoing Hematopoietic Cell Transplant (HCT) J. Clin. Pharmacol., April 1, 2008; 48(4): 485 - 494. [Abstract] [Full Text] [PDF] H. J. Deeg How I treat refractory acute GVHD Blood, May 15, 2007; 109(10): 4119 - 4126. [Abstract] [Full Text] [PDF] P. Jacobson, K. Green, J. Rogosheske, C. Brunstein, B. Ebeling, T. DeFor, P. McGlave, and D. Weisdorf Highly Variable Mycophenolate Mofetil Bioavailability Following Nonmyeloablative Hematopoietic Cell Transplantation J. Clin. Pharmacol., January 1, 2007; 47(1): 6 - 12. [Abstract] [Full Text] [PDF] M. A. Schroeder, J. F. DiPersio, M. P. Rettig, and J. K. Ritchey Forced Expression of the "IY" Mutant Inosine Monophosphate Dehydrogenase II Results in Physiologically Significant Resistance to Mycophenolic Acid In Vitro. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 5480 - 5480. [Abstract] [PDF]

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