Tacrolimus levels are not associated with risk of malignancy in lung transplant recipients

Benjamin Daniel Fox, Fadi Ashquar, Yael Raviv, Dror Rozengarten, Osnat Straichman, Shimon Izhakian, Mordechai Reuven Kramer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Lung transplant (LTx) recipients suffer from high rates of malignancy. Exposure to immunosuppressive medication such as tacrolimus has been proposed as a risk factor for tumorigenesis. We hypothesized that chronically high levels of tacrolimus would be associated with risk of malignancy. Material/Methods: The study was performed in a transplant center in Israel, with a nested case-control design. Cases were LTx recipients who were diagnosed with any solid or hematological malignancy except non-melanoma skin cancer. Controls were tumor-free during their entire follow-up after LTx and had at least the same follow-up time as their matched case. Controls were matched to cases by age and type of transplant received (single/double). Tacrolimus levels were extracted and analyzed for median drug level and also integrated over time (area under the curve – AUC-tacrolimus). Results: We reviewed 412 LTx recipients in our registry. Thirty-nine cases of malignancy were diagnosed and 160 controls were matched, giving a crude tumor incidence rate of 26/100 000/year. Lung cancers were the commonest diagnosis. Cases and controls were well matched by age, smoking status, and LTx type. Median tacrolimus levels were 11.0 ng/ml and 11.3 ng/ml in cases and controls, respectively (p=0.88). The median log (AUC-tacrolimus) was 9.4 in the cases and 9.5 in the controls (p=0.59). Conclusions: In this nested case-control study, exposure to tacrolimus was similar in tumor cases and non-tumor controls. These data, based on a cohort with modest size, suggest either that tumorigenesis in LTx recipients is unrelated to tacrolimus exposure or that levels in these patients are above an unknown threshold at which the doseresponse effect is saturated.

Original languageEnglish
Pages (from-to)677-681
Number of pages5
JournalAnnals of Transplantation
Volume22
DOIs
StatePublished - 1 Jan 2017
Externally publishedYes

Keywords

  • Carcinogenesis
  • Case-control studies
  • Immunosuppressive agents
  • Lung transplantation
  • Neoplasms
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

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