Tacrolimus in adult hematopoietic stem cell transplantation

ABSTRACT

Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients.

Areas covered: This review introduces phase II/III of clinical trials related with Tac’s roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients.

Expert opinion: A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.

KEYWORDS:

• Tacrolimus
• hematopoietic stem cell transplantation
• graft-versus-host disease
• immunosuppression
• tacrolimus concentration
• pharmacogenetics
• side effects

Article highlights

• The target ranges of the Tac concentration seem to be 10–20 ng/mL, and higher blood levels (>12 ng/mL) are suggested by several studies during the initial first week post HSCT.

• CYP3A5, CYP3A4, and ABCB1 polymorphism were found to affect Tac dosage in HSCT.

• Because fluconazole has less influence upon Tac levels than other azoles, it seems to be the most appropriate azole antifungal agent in Tac therapy after HSCT.

• Novel agents that have shown promising results in the prevention of GVHD in phase Ⅰ/Ⅱ trials include bort, rATG, MVC, and PTCY in combination with Tac.

• Nephrotoxicity, neurotoxicity, and pain syndrome are relatively common toxicities caused by Tac in HSCT.

This box summarizes key points contained in the article.

Author Contributions Statement

JJ Ma designed the review and Y Gao wrote the first draft of the manuscript. JJ Ma and Y Gao reviewed the manuscript and made critical revisions. Both authors read and approved the final version of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper is supported by Chinese National Natural Science Foundation (No. 8140130232).