Rituximab for steroid-refractory chronic graft-versus-host disease.

Abstract

B cells may be implicated in the pathophysiology of chronic graft-versus-host disease (GVHD), as evidenced by antibody production against sex-mismatched, Y chromosome-encoded minor HLA antigens in association with chronic GVHD. We therefore designed a phase 1/2 study of anti-B-cell therapy with rituximab in steroid-refractory chronic GVHD. Twenty-one patients were treated with 38 cycles of rituximab. Rituximab was tolerated well, and toxicity was limited to infectious events. The clinical response rate was 70%, including 2 patients with complete responses. Responses were limited to patients with cutaneous and musculoskeletal manifestations of chronic GVHD and were durable through 1 year after therapy. The median dose of prednisone among treated subjects fell from 40 mg/day to 10 mg/day, 1 year after rituximab therapy (P < .001). A chronic GVHD symptom score improved in the majority of treated patients. Antibody titers against Y chromosome-encoded minor HLA antigens fell and remained low, whereas titers against infectious antigens (EBV, tetanus) remained stable or rose during the treatment period. We conclude that specific anti-B-cell therapy with rituximab may be beneficial for patients with steroidrefractory chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00136396.

• Authors: Corey Cutler, David Miklos, Haesook T Kim, Nathaniel Treister, Sook-Bin Woo, Don Bienfang, Lloyd B Klickstein, Jesse Levin, Katherine Miller, Carol Reynolds, Rebecca Macdonell, Mildred Pasek, Stephanie J Lee, Vincent Ho, Robert Soiffer, Joseph H Antin, Jerome Ritz, Edwin Alyea
• Journal: Blood (Blood) Vol. 108 Issue 2 Pg. 756-62 (Jul 15 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16551963 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Steroids
• Rituximab
• Prednisone

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Murine-Derived
• B-Lymphocytes (drug effects, pathology)
• Chronic Disease
• Drug Resistance
• Female
• Graft vs Host Disease (drug therapy, pathology)
• Humans
• Male
• Middle Aged
• Musculoskeletal Diseases (drug therapy, etiology)
• Prednisone (pharmacology)
• Rituximab
• Salvage Therapy (methods)
• Skin Diseases (drug therapy, etiology)
• Steroids (pharmacology)