title: FK506 (tacrolimus) in the treatment of steroid-resistant acute graft-versus-host disease in children undergoing bone marrow transplantation.
abstract: Steroid-resistant graft-versus-host disease (GVHD) is an often lethal complication of bone marrow transplantation (BMT). FK506 (tacrolimus) is a new potent immunosuppressant which has been shown to be superior to conventional immunosuppression in the prevention and treatment of graft rejection in recipients of solid organ transplants. To determine whether FK506 is effective in the treatment of steroid-resistant acute GVHD, 6 children with biopsy-proven severe GVHD were studied. FK506 was administered as intravenous or oral therapy and the dose was adjusted to achieve serum levels between 0.5 and 1.0 microgram/ml by ELISA. Steroid doses were tapered based on clinical grading in each organ. Within 1-2 days, improvement occurred in skin and gut in all patients, and in liver in 3 patients. Toxicity attributable to FK506 was similar to that described in solid organ transplant patients and included neurotoxicity, nephrotoxicity and gastrointestinal effects. While FK506 is effective in the treatment of steroid-resistant acute GVHD, toxicity may limit its use. Further studies evaluating FK506 as GVHD prophylaxis and treatment of less advanced GVHD are needed.
authors.affiliation: Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, PA 15213-2583, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Koehler
authors.forename: D
authors.initials: D
authors.lastname: Howrie
authors.forename: J
authors.initials: J
authors.lastname: Mirro
authors.forename: S
authors.initials: S
authors.lastname: Neudorf
authors.forename: J
authors.initials: J
authors.lastname: Blatt
authors.forename: S
authors.initials: S
authors.lastname: Corey
authors.forename: M
authors.initials: M
authors.lastname: Wollman
authors.forename: V
authors.initials: V
authors.lastname: Kelly-Ekeroth
authors.forename: J
authors.initials: J
authors.lastname: Reyes
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D016879:Salvage Therapy; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011239:Prednisolone; D016559:Tacrolimus