Successful treatment of steroid-resistant severe acute GVHD with 24-h continuous infusion of FK506

• Published in: Bone marrow transplantation (Basingstoke) Vol. 19; no. 6; pp. 625 - 627
• Main Authors: OHASHI, Y, MINEGISHI, M, FUJIE, H, TSUCHIYA, S, KONNO, T
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.1997
• Subjects: Acute Disease; Adolescent; Biological and medical sciences; Bone Marrow Transplantation; Child; Complications; Diarrhea; Drug Resistance; Erythema; Female; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Histocompatibility antigen HLA; Humans; Immunomodulators; Immunosuppressive Agents - administration & dosage; Infusions, Intravenous; Intravenous administration; Intravenous infusion; Leukemia, Myeloid, Acute - therapy; Medical sciences; Patients; Pharmacology. Drug treatments; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prednisolone - therapeutic use; Skin diseases; Stem cell transplantation; Steroids; Tacrolimus; Tacrolimus - administration & dosage; Transplantation, Homologous; Human; Immunopathology; Corticosteroid; Transfusion; Intravenous administration; Continuous; Acute; Homograft; Graft versus host reaction; Malignant hemopathy; Case study; Chemotherapy; Treatment; Tacrolimus; Perfusion; Lymphoproliferative syndrome; Adolescent; Bone marrow; Complication; Graft; Immunosuppressive agent; Acute lymphocytic leukemia; Child; Negative therapeutic reaction
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1700716

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.