Initial tacrolimus weight-based dosing strategy in allogeneic hematopoietic stem-cell transplantation

Area of Science:

• Hematology
• Immunology
• Pharmacology

Background:

• Tacrolimus is crucial for graft-versus-host disease (GVHD) prophylaxis post-hematopoietic stem-cell transplantation (HSCT).
• Therapeutic tacrolimus levels are essential for preventing acute GVHD (aGVHD), while excessive levels risk toxicity and relapse.

Purpose of the Study:

• To evaluate the achievement of initial therapeutic tacrolimus levels using empiric weight-based dosing.
• To assess the incidence of tacrolimus toxicity, aGVHD, and relapse in patients receiving continuous intravenous tacrolimus infusion.

Main Methods:

• Retrospective chart review of adult patients undergoing allogeneic HSCT.
• Analysis of patients receiving initial tacrolimus continuous intravenous infusion for GVHD prophylaxis.
• Primary outcome: percentage of patients achieving therapeutic tacrolimus levels (5-12 ng/mL).

Main Results:

• Only 47% of patients achieved initial therapeutic tacrolimus levels, with a median level of 12.4 ng/mL.
• Over half (52%) of patients experienced supratherapeutic levels.
• No significant nephrotoxicity, hepatotoxicity, or neurotoxicity was observed within the first week or at neutrophil engraftment.
• Grade II-IV aGVHD by day 100 occurred in 22% of patients; 16% experienced relapse after six months.

Conclusions:

• Empiric weight-based dosing of tacrolimus for GVHD prophylaxis often leads to supratherapeutic levels.
• Low observed toxicity suggests potential for dose reduction or an expanded therapeutic target range (5-15 ng/mL).
• These findings may inform optimized tacrolimus dosing strategies to balance efficacy and safety in HSCT recipients.