Relationship of tacrolimus (FK506) whole blood concentrations and efficacy and safety after HLA-identical sibling bone marrow transplantation

John R. Wingard, Richard A. Nash, Donna Przepiorka, Jared L. Klein, Daniel J. Weisdorf, Joseph W. Fay, Jin Zhu, Rochelle M. Maher, William E. Fitzsimmons, Voravit Ratanatharathorn

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

A randomized clinical trial comparing tacrolimus with cyclosporine, both with short-course methotrexate, as prophylaxis against graft-vs.-host disease (GVHD) in allogeneic HLA-matched sibling bone marrow transplant patients was conducted. Cyclosporine was dosed to achieve a target concentration range between 150 and 450 ng/mL during the first 8 weeks after transplant. For tacrolimus, the target concentration range was 10-30 ng/mL during the first 8 weeks after transplant. A gradual tapering schedule of 20% per month during months 3-6 was then conducted for patients in both treatment arms. The efficacy of the immunosuppressive regimen was determined by the rate of acute GVHD grades II-IV. The toxicity of the immunosuppressive regimen was determined by the occurrence of the creatinine exceeding 2 mg/dL, the creatinine doubling the baseline value, or the necessity for hemodialysis. Correlations between blood concentrations and efficacy and toxicity parameters were assessed. For both tacrolimus and cyclosporine, increasing blood concentrations were associated with greater renal dysfunction. For cyclosporine, there was a nonsignificant trend to an increased incidence of grades II-IV acute GVHD with lower cyclosporine blood concentrations (<300 ng/mL). In contrast, there did not appear to be a relationship between the blood concentrations of tacrolimus and the occurrence of acute GVHD. This suggests that optimization of efficacy while minimizing the risk for nephrotoxicity could be achieved by dosing tacrolimus to a targeted range between 10 and 20 ng/mL.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume4
Issue number3
DOIs
StatePublished - 1998

Keywords

  • Cyclosporine
  • Graft-vs.-host disease
  • Immunosuppression

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