Biology of Blood and Marrow Transplantation
Volume 16, Issue 3 , Pages 333-343 , March 2010

An Age-Dependent Pharmacokinetic Study of Intravenous and Oral Mycophenolate Mofetil in Combination with Tacrolimus for GVHD Prophylaxis in Pediatric Allogeneic Stem Cell Transplantation Recipients

  • Monica Bhatia

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Olga Militano

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Zhezhen Jin

      Affiliations

    • Department of Biostatistics, Columbia University, New York, New York
    • ,
  • Michal Figurski

      Affiliations

    • Department of Pathology & Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
    • ,
  • Leslie Shaw

      Affiliations

    • Department of Pathology & Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
    • ,
  • Virginia Moore

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Erin Morris

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Bradford Tallamy

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Carmella van deVen

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Janet Ayello

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • LeeAnn Baxter-Lowe

      Affiliations

    • Department of Surgery, University of California, San Francisco, California
    • ,
  • Prakash Satwani

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Diane George

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • M. Brigid Bradley

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • James Garvin

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • ,
  • Mitchell S. Cairo

      Affiliations

    • Department of Pediatrics, Columbia University, New York, New York
    • Department of Medicine, Columbia University, Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital, New York, New York
    • Department of Pathology, Columbia University, Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital, New York, New York
    • Corresponding Author InformationCorrespondence and reprint requests: Mitchell S. Cairo, MD, Division of Pediatric Blood and Marrow Transplantation, Pediatrics, Medicine, Pathology, Columbia University, 3959 Broadway, CHN 10-03, New York, NY 10032.

References 

  1. Cairo M, Heslop H. Pediatric blood and marrow transplantation: state of the science. Bone Marrow Transplant. 2008;41:97
  2. Chao N. Graft Versus Host Disease. Austin, TX: R.G. Landes Co; 1999;
  3. Ferrara JL, Levy R, Chao NJ. Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol Blood Marrow Transplant. 1999;5:347–356
  4. Jacobsohn DA. Acute graft-versus-host disease in children. Bone Marrow Transplant. 2008;41:215–221
  5. Mrsic M, Labar B, Bogdanic V, et al. Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation for leukemia. Bone Marrow Transplant. 1990;6:137–141
  6. Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986;314:729–735
  7. Jensen CW, Flechner SM, Van Buren CT, et al. Exacerbation of cyclosporine toxicity by concomitant administration of erythromycin. Transplantation. 1987;43:263–270
  8. Lazarus HM, Coccia PF, Herzig RH, et al. Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients. Blood. 1984;64:215–220
  9. Thompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet. 1984;2:1116–1120
  10. Lin CS, Boltz RC, Siekierka JJ, Sigal NH. FK-506 and cyclosporin A inhibit highly similar signal transduction pathways in human T lymphocytes. Cell Immunol. 1991;133:269–284
  11. Peters DH, Fitton A, Plosker GL, Faulds D. Tacrolimus. A review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs. 1993;46:746–794
  12. Hiraoka A, Ohashi Y, Okamoto S, et al. Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2001;28:181–185
  13. Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96:2062–2068
  14. Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998;92:2303–2314
  15. Basara N, Blau WI, Romer E, et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant. 1998;22:61–65
  16. Bornhauser M, Schuler U, Porksen G, et al. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Transplantation. 1999;67:499–504
  17. Dvorak CC, Callard E, Agarwal R. Use of intravenous mycophenolate mofetil for graft-versus-host disease prophylaxis in an allogeneic hematopoietic stem cell transplant recipient with an allergic reaction to cyclosporine and tacrolimus. Bone Marrow Transplant. 2006;38:253–254
  18. Haentzschel I, Freiberg-Richter J, Platzbecker U, et al. Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Bone Marrow Transplant. 2008;42:113–120
  19. Mohty M, de Lavallade H, Faucher C, et al. Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant. 2004;34:527–530
  20. Osunkwo I, Bessmertny O, Harrison L, et al. A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients. Biol Blood Marrow Transplant. 2004;10:246–258
  21. Shapira MY, Hirshfeld E, Weiss L, et al. Mycophenolate mofetil does not suppress the graft-versus-leukemia effect or the activity of lymphokine-activated killer (LAK) cells in a murine model. Cancer Immunol Immunother. 2005;54:383–388
  22. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304
  23. Tsina I, Chu F, Hama K, et al. Manual and automated (robotic) high-performance liquid chromatography methods for the determination of mycophenolic acid and its glucuronide conjugate in human plasma. J Chromatogr. 1996;675:119–129
  24. Figurski M, Korecka M, Fields L, Waligorska T, Shaw L. HPLC-MS/MS method for simultaneous quantification of total or free fraction of mycophenolic acid and its glucuronide metabolites. Ther Drug Monit. 2007;29:511–512
  25. Gibaldi M. Biopharmaceutics and Clinical Pharmacokinetics. Biopharmaceutics and Clinical Pharmacokinetics. Philadelphia, PA: Lea and Febiger; 1984;315-316
  26. Jacobson P, Huang J, Rydholm N, et al. Higher mycophenolate dose requirements in children undergoing hematopoietic cell transplant (HCT). J Clin Pharmacol. 2008;48:485–494
  27. Nash RA, Johnston L, Parker P, et al. A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005;11:495–505
  28. Papadimitriou JC, Cangro CB, Lustberg A, et al. Histologic features of mycophenolate mofetil-related colitis: a graft-versus-host disease-like pattern. Int J Surg Pathol. 2003;11:295–302
  29. Baron F, Sandmaier BM, Storer BE, et al. Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2007;13:1041–1048
  30. Giaccone L, McCune JS, Maris MB, et al. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Blood. 2005;106:4381–4388
  31. Jenke A, Renner U, Richte M, et al. Pharmacokinetics of intravenous mycophenolate mofetil after allogeneic blood stem cell transplantation. Clin Transplant. 2001;15:176–184
  32. Bullingham R, Monroe S, Nicholls A, Hale M. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clinl Pharmacol. 1996;36:315–324
  33. Shaw LM, Holt DW, Oellerich M, Meiser B, van Gelder T. Current issues in therapeutic drug monitoring of mycophenolic acid: report of a roundtable discussion. Ther Drug Monit. 2001;23:305–315
  34. Shaw LM, Korecka M, Venkataramanan R, Goldberg L, Bloom R, Brayman KL. Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies. Am J Transplant. 2003;3:534–542
  35. Shaw LM, Mick R, Nowak I, Korecka M, Brayman KL. Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function. J Clin Pharmacol. 1998;38:268–275
  36. Kagaya H, Miura M, Satoh S, et al. No pharmacokinetic interactions between mycophenolic acid and tacrolimus in renal transplant recipients. J Clin Pharmacy Therapeut. 2008;33:193–201
  37. van Gelder T, Shaw LM. The rationale for and limitations of therapeutic drug monitoring for mycophenolate mofetil in transplantation. Transplantation. 2005;80:S244–253
  38. Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet. 1998;34:429–455
  39. Arns W, Cibrik DM, Walker RG, et al. Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature. Transplantation. 2006;82:1004–1012
  40. Gregoor PJ, de Sevaux RG, Hene RJ, et al. Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients. Transplantation. 1999;68:1603–1606
  41. Shaw LM, Nawrocki A, Korecka M, Solari S, Kang J. Using established immunosuppressant therapy effectively: lessons from the measurement of mycophenolic acid plasma concentrations. Ther Drug Monit. 2004;26:347–351
  42. Rea RS, Capitano B, Bies R, Bigos KL, Smith R, Lee H. Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit. 2008;30:674–681
  43. Trager K, DeBacker D, Radermacher P. Metabolic alterations in sepsis and vasoactive drug-related metabolic effects. Curr Opin Crit Care. 2003;9:271–278

 Financial disclosure: See Acknowledgments on page 341.

 The first 2 authors should be considered equal coprimary first authors.

PII: S1083-8791(09)00463-7

doi: 10.1016/j.bbmt.2009.10.007

Biology of Blood and Marrow Transplantation
Volume 16, Issue 3 , Pages 333-343 , March 2010

Article Tools

* Image Usage & Resolution