Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acutegraft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities

This retrospective study describes the outcome in 53 patients who had immun osuppressive treatment changed from cyclosporine (CSP) to tacrolimus for re sistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CS P-associated neurotoxicity (n = 17), Tacrolimus was administered at doses o f 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, a s tolerated. Median time of conversion to tacrolimus after transplant was d ay 47, Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades LII or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution o f GVHD after changing treatment to tacrolimus, with 18 showing no improveme nt, Eleven evaluable patients had therapy changed to tacrolimus for CSP-ass ociated neurotoxicity at a median of 36 days after transplant. Eight patien ts had resolution of neurotoxicity and three had partial improvement. Eleve n evaluable patients had therapy changed to tacrolimus for HUS at a median of 46 days after transplant. One patient had complete resolution of HUS and 10 showed no response, Side-effects related to tacrolimus included renal t oxicity (34%), neurotoxicity (15%) and HUS (9%), Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CS P-associated neurotoxicity, While often successful for dealing with neuroto xicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD.