title: Successful treatment of steroid-resistant severe acute GVHD with 24-h continuous infusion of FK506.
abstract: We report our findings in two cases of steroid-resistant severe acute GVHD after allogeneic BMT successfully treated with FK506 (tacrolimus). An 18-year-old female (patient 1) who underwent BMT from an HLA-identical sibling for ALL in first CR, developed generalized erythema and profuse watery diarrhea, which progressed to acute GVHD of grade III severity, resistant to steroid control. After continuous 24-h administration of FK506, the diarrhea improved within 10 days. Patient 2, a 9-year-old girl with AML who underwent unrelated BMT, had skin, gut and liver lesions of acute GVHD grade IV, which did not respond to high-dose steroid therapy. They were controlled, however, by continuous intravenous infusion of FK506. Both patients are still surviving after more than 1 year without any acute GVHD sequelae or signs of chronic illness. The adverse effects of FK506 were mild and tolerable in both cases. Comparison of our findings with those in the literature suggests that it is important to give FK506 at plasma concentrations as high as 25-35 ng/ml by continuous intravenous infusion for extended periods to control steroid-resistant severe acute GVHD.
authors.affiliation: Institute of Development, Aging, and Cancer, Tohoku University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: M
authors.initials: M
authors.lastname: Minegishi
authors.forename: H
authors.initials: H
authors.lastname: Fujie
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: T
authors.initials: T
authors.lastname: Konno
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D016026:Bone Marrow Transplantation; D002648:Child; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011239:Prednisolone / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone; D016559:Tacrolimus