Marrow graft rejection and veno-occlusive disease of the liver in patients with aplastic anemia conditioned with cyclophosphamide and cyclosporine.
Based on studies in multiply transfused dogs showing that cyclosporine (CsA) pregrafting reduced the incidence of rejection, we treated 11 multiply transfused patients with severe aplastic anemia with CsA, 12.5-20 mg/kg/day i.m. on days -6 to -1, and cyclophosphamide, 50 mg/kg/day i.v. on days -5 to -2, followed on day 0 by a marrow graft from an HLA-identical sibling donor. Patients were not given additional infusions of buffy coat cells from their marrow donors. As postgrafting prophylaxis for graft-versus-host disease 10 patients were given CsA, 12.5 mg/kg/day orally, and one patient was given a standard regimen of intermittent methotrexate. Among 10 evaluable patients, 2 rejected their marrow grafts. Eight patients had sustained engraftment. Two of these developed severe veno-occlusive disease of the liver, a complication previously observed only in patients conditioned with total-body irradiation but not in more than 200 patients with aplastic anemia conditioned with cyclophosphamide without the addition of CsA. These data indicate that conditioning of patients with cyclophosphamide and concurrent CsA does not uniformly prevent graft rejection and can result in severe hepatic toxicity.
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000009:adverse effects*; D003524:Cyclosporins / Q000009:adverse effects* / Q000097:blood; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000209:etiology; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male
D003524:Cyclosporins; D003520:Cyclophosphamide