Relationship between tacrolimus blood concentrations and clinical outcome during the first 4 weeks after SCT in children

N. Watanabe, K. Matsumoto, H. Muramatsu, K. Horibe, T. Matsuyama, S. Kojima, K. Kato

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

The relationship between tacrolimus concentration and acute GVHD is not well known, with few published data available for lower target levels. We hypothesized that lower levels of tacrolimus would correlate with higher incidence of acute GVHD and poorer prognosis. Receiver operator characteristic curves (ROC) were used to quantify tacrolimus blood levels as predictors of grade II-IV acute GVHD. A total of 97 pediatric patients with hematological malignancies met the study criteria. On the ROC, a cutoff of 7 ng/ml provided the best balance between sensitivity and specificity (62.8 vs 68.2%, respectively). Cumulative incidence of acute GVHD was 65.9% (range 58.5-73.3%) in patients with mean tacrolimus concentration of 7 ng/ml and 34.8% (range 27.8-41.8%) in patients with mean tacrolimus concentration of 7 ng/ml (P0.002). Incidence of non-relapse mortality (NRM) was higher in patients with tacrolimus of 7 ng/ml (42.9%; range 35.6-50.2%) than in patients with tacrolimus of 7 ng/ml (28.3%; range 17.4-39.2%; P0.008). This translated into better EFS in patients with tacrolimus of 7 ng/ml (48.9%; range 39.8-58.0%) than in patients with tacrolimus of 7 ng/ml (31.8%; range 25.0-38.6%; P0.031). Multivariate analysis showed that tacrolimus concentration was significantly associated with clinical outcomes. Mean whole-blood level of tacrolimus as continuous infusion should be maintained at 7 ng/ml for pediatric patients.

Original languageEnglish
Pages (from-to)1161-1166
Number of pages6
JournalBone Marrow Transplantation
Volume45
Issue number7
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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