Biology of Blood and Marrow Transplantation
Volume 10, Issue 4 , Pages 246-258, April 2004

A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients

  • Ifeyinwa Osunkwo

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Olga Bessmertny

      Affiliations

    • Department of Pharmacy, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Lauren Harrison

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Ying-Kuen Cheung

      Affiliations

    • Division of Biostatistics,, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Carmella Van De Ven

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Gustavo del Toro

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • James Garvin

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Diane George

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • M.Brigid Bradley

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Karen Wolownik

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Cheryl Wischhover

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Joseph Levy

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Donna Skerrett

      Affiliations

    • Department of Pathology, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • ,
  • Mitchell S Cairo

      Affiliations

    • Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Columbia University, New York, New York, USA
    • Corresponding Author InformationCorrespondence and reprint requests: Mitchell S. Cairo, MD, Columbia University, 161 Fort Washington Ave., 7th Floor, Room 754, New York, NY 10032 USA

Received 28 July 2003; accepted 19 November 2003.

Abstract 

Tacrolimus (FK506)/mycophenolate mofetil (MMF) has been demonstrated to be an effective salvage therapy for steroid-resistant chronic graft-versus-host disease (GVHD), but its effectiveness as prophylaxis for acute GVHD (aGVHD) is unknown. We investigated the safety and efficacy of FK506/MMF in preventing aGVHD and sparing the use of methotrexate and methylprednisolone in childhood and adolescent allogeneic stem cell transplant (AlloSCT) recipients. Thirty-four childhood and adolescent patients (median age, 7 years; range, 0.5–21 years; 24 males and 10 females) undergoing 37 AlloSCTs for malignant (n = 22) and nonmalignant (n = 12) disorders received FK506 (0.03 mg/kg/d by continuous intravenous infusion) and MMF (15 mg/kg per dose orally or intravenously twice daily). Stem cell sources included 22 umbilical cord blood donors (21 unrelated and 1 related), 6 related bone marrow donors, and 9 related peripheral blood donors. Malignant diagnoses included 7 acute lymphoblastic leukemias, 3 acute myeloid leukemias, 1 acute promyelocytic leukemia, 2 non-Hodgkin lymphomas, 4 Hodgkin diseases, 3 chronic myeloid leukemias, and 2 neuroblastomas; nonmalignant diagnoses included 2 β-thalassemias, 1 sickle cell disease, 4 aplastic anemias, 1 Wiskott-Aldrich syndrome, 1 Hurler syndrome, 2 hemophagocytic lymphohistiocytoses, and 1 myelodysplastic syndrome. The probability of developing grade ≥II aGVHD was 45.4% ± 9.7% (7 related bone marrow/related peripheral blood; 5 umbilical cord blood), and for chronic GVHD it was 38.1% ± 19.7%. FK506/MMF was well tolerated. Three patients had grade III to IV neurotoxicity (disorientation and leukoencephalopathy); 4 patients developed grade III to IV nephrotoxicity (all received concomitant nephrotoxins). Patients who achieved target mycophenolic acid levels (1.0–3.5 μg/mL) before day +30 had a significantly reduced incidence of developing grade ≥II aGVHD (16.7% ± 15.2% versus 100%; P < .02). These results suggest that FK506/MMF is well tolerated and may be a safe and effective methotrexate- and methylprednisolone-sparing alternative GVHD prophylaxis regimen after AlloSCT. Further pharmacokinetic and pharmacodynamic studies are ongoing in pediatric and adolescent AlloSCT recipients to define optimal MMF dosing.

Keywords:  Tacrolimus, Mycophenolate mofetil, Graft-versus-host disease, Allogeneic stem cell transplantation

 

PII: S1083-8791(03)00480-4

doi:10.1016/j.bbmt.2003.11.005

Biology of Blood and Marrow Transplantation
Volume 10, Issue 4 , Pages 246-258, April 2004

Article Tools

* Image Usage & Resolution