Practical considerations in the use of tacrolimus for allogeneic marrow transplantation

Abstract

Tacrolimus has been shown to be more effective than cyclosporine for prevention of acute graft-versus-host disease (GVHD). A number of transplant centers have therefore adopted tacrolimus as standard prophylaxis, but with additional experience, current management of tacrolimus differs from that in the clinical studies. Therefore, a consensus conference was convened to assess the current practices. For prevention of GVHD, conference participants recommended administering tacrolimus at 0.03 mg/kg/day (by lean body weight) i.v. by continuous infusion from day −1 or −2 pretransplant, with day −2 used especially for pediatric patients. Therapeutic drug monitoring was considered essential in the management of patients on tacrolimus. The consensus target range for the whole blood concentration was 10–20 ng/ml. Doses were modified for blood levels outside the target range or for nephrotoxicity, and tacrolimus was discontinued for intolerable tremor, hemolytic uremic syndrome, leukoencephalopathy or other serious toxicity. Tacrolimus was employed most frequently in combination with minimethotrexate (5 mg/m² i.v. days 1, 3, 6 and 11). Tapering was individualized according to center practice. No patient category was excluded from use of tacrolimus based on age, extent of disease, patient–donor histocompatibility or stem cell source. Tacrolimus was also used successfully for treatment of chronic GVHD. The responsiveness of steroid-refractory acute GVHD was marginal, so it was deemed more prudent to use tacrolimus for prophylaxis instead.