title: Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin.
abstract: The A chain of the toxin ricin has been conjugated by a disulfide bond to a murine monoclonal antibody that recognizes the CD5 (T,p67) antigen present on 95% of peripheral blood T lymphocytes. This immunotoxin was used to treat a patient with severe grade III-IV, steroid-resistant, acute graft-vs-host disease (GvHD) after an allogeneic, human leukocyte antigen-identical bone marrow transplant for acute myelogenous leukemia. Immunotoxin therapy produced a complete clinical response in the skin and gastrointestinal tract. The patient tolerated a 14-day course without symptoms or signs of toxic effects. After two days of therapy, circulating T cells could not be demonstrated by indirect immunofluorescence. After therapy, acute GvHD did not recur. However, seven months after therapy the patient demonstrated mild signs of chronic GvHD that were easily controlled with low-dose immunosuppressive therapy. These findings indicate that an anti-T-cell ricin A chain immunotoxin can be given safely for treatment of acute GvHD and may be an effective therapy for this significant posttransplant complication.
authors.affiliation: Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: N A
authors.initials: NA
authors.lastname: Kernan
authors.forename: V
authors.initials: V
authors.lastname: Byers
authors.forename: P J
authors.initials: PJ
authors.lastname: Scannon
authors.forename: R P
authors.initials: RP
authors.lastname: Mischak
authors.forename: J
authors.initials: J
authors.lastname: Brochstein
authors.forename: N
authors.initials: N
authors.lastname: Flomenberg
authors.forename: B
authors.initials: B
authors.lastname: Dupont
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Reilly
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D016026:Bone Marrow Transplantation; D002648:Child; D004351:Drug Resistance; D005260:Female; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008775:Methylprednisolone / Q000627:therapeutic use; D012276:Ricin / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012276:Ricin; D008775:Methylprednisolone