Practical considerations in the use of tacrolimus for allogeneic marrow transplantation

Tacrolimus has been shown to be more effective than cyclosporine for preven tion of acute graft-versus-host disease (GVHD), A number of transplant cent ers have therefore adopted tacrolimus as standard prophylaxis, but with add itional experience, current management of tacrolimus differs from that in t he clinical studies. Therefore, a consensus conference was convened to asse ss the current practices. For prevention of GVHD, conference participants r ecommended 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 u sed especially for pediatric patients. Therapeutic drug monitoring was cons idered 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 sy ndrome, leukoencephalopathy or other serious toxicity. Tacrolimus was emplo yed most frequently in combination with minimethotrexate (5 mg/m(2) i.v. da ys 1, 3, 6 and 11), Tapering was individualized according to center practic e. No patient category was excluded from use of tacrolimus based on age, ex tent of disease, patient-donor histocompatibility or stem cell source. Tacr olimus was also used successfully for treatment of chronic GVHD, The respon siveness of steroid-refractory acute GVHD was marginal, so it was deemed mo re prudent to use tacrolimus for prophylaxis instead.