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

Abstract

Summary:This retrospective study describes the outcome in 53 patients who had immunosuppressive treatment changed from cyclosporine (CSP) to tacrolimus for resistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CSP-associated neurotoxicity (n = 17). Tacrolimus was administered at doses of 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, as tolerated. Median time of conversion to tacrolimus after transplant was day 47. Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades III or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution of GVHD after changing treatment to tacrolimus, with 18 showing no improvement. Eleven evaluable patients had therapy changed to tacrolimus for CSP-associated neurotoxicity at a median of 36 days after transplant. Eight patients had resolution of neurotoxicity and three had partial improvement. Eleven 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 toxicity (34%), neurotoxicity (15%) and HUS (9%). Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CSP-associated neurotoxicity. While often successful for dealing with neurotoxicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD. Bone Marrow Transplantation (2000) 26, 985-991.

Posterior Reversible Encephalopathy Syndrome after Solid Organ Transplantation

“…18 Although blood levels of cyclosporine and tacrolimus tend not to correlate with PRES, medication withdrawal often results in alleviation of toxicity. 33,34 The cause of neurotoxicity with PRES remains controversial. From a historical persective, hypertension with failed autoregulation and hyperperfusion has been suggested as the cause of the developing vasogenic edema.…”

How I treat refractory acute GVHD

“…A switch from cyclosporine to tacrolimus in our hands was useful only in patients in whom the switch occurred because of neurotoxicity. 60 Phototherapy pursues a different strategy. Based on initial observations in patients with cutaneous T-cell lymphoma or various dermatologic disorders, 8-methoxypsoralen is given to patients orally before external exposure to ultraviolet irradiation in the UVA range (320-400 nm) to sensitize circulating T lymphocytes to UV energy.…”

Prevention and treatment of acute GvHD

“…44,45 Switching from CsA to FK506 proved to be beneficial for 12% of patients. 46 ATG was another option for steroid-resistant patients. Unfortunately, a prospective randomized Group for Marrow Transplantation study showed no difference between patients who were randomized to receive 2 mg/kg of 6MPD for 10 days alone and those who were administered 6MPD associated with rabbit ATG.…”