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

• Published in: Blood Vol. 108; no. 2; pp. 756 - 762
• Main Authors: Cutler, Corey, Miklos, David, Kim, Haesook T., Treister, Nathaniel, Woo, Sook-Bin, Bienfang, Don, Klickstein, Lloyd B., Levin, Jesse, Miller, Katherine, Reynolds, Carol, Macdonell, Rebecca, Pasek, Mildred, Lee, Stephanie J., Ho, Vincent, Soiffer, Robert, Antin, Joseph H., Ritz, Jerome, Alyea, Edwin
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.07.2006; The Americain Society of Hematology; The American Society of Hematology
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Murine-Derived; B-Lymphocytes - drug effects; B-Lymphocytes - pathology; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Chronic Disease; Drug Resistance; Female; Graft vs Host Disease - drug therapy; Graft vs Host Disease - pathology; Humans; Male; Medical sciences; Middle Aged; Musculoskeletal Diseases - drug therapy; Musculoskeletal Diseases - etiology; Prednisone - pharmacology; Rituximab; Salvage Therapy - methods; Skin Diseases - drug therapy; Skin Diseases - etiology; Steroids - pharmacology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Human; Steroid; Immunopathology; Treatment resistance; Chronic disease; Stem cell; Hematopoietic cell; Homograft; Rituximab; Graft versus host reaction; Monoclonal antibody; Treatment; Immunotherapy; Anticytokine; Graft
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2006-01-0233

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.