title: Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation.
abstract: Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: B J
authors.initials: BJ
authors.lastname: Nelson
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
authors.forename: G B
authors.initials: GB
authors.lastname: McDonald
authors.forename: R A
authors.initials: RA
authors.lastname: Nash
authors.forename: K M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: R P
authors.initials: RP
authors.lastname: Witherspoon
authors.forename: P J
authors.initials: PJ
authors.lastname: Scannon
authors.forename: N
authors.initials: N
authors.lastname: Friedmann
authors.forename: R
authors.initials: R
authors.lastname: Storb
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D018956:CD5 Antigens / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007674:Kidney Diseases / Q000139:chemically induced; D008212:Lymphocyte Depletion; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D012276:Ricin / Q000009:adverse effects / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018956:CD5 Antigens; D007166:Immunosuppressive Agents; D000922:Immunotoxins; C059257:XomaZyme; D012276:Ricin; D008775:Methylprednisolone