Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence.

Abstract

B cells are involved in the pathogenesis of chronic GVHD (cGVHD). We hypothesized that prophylactic anti-B-cell therapy delivered 2 months after transplantation would decrease allogeneic donor B-cell immunity and possibly the incidence of cGVHD. Therefore, in the present study, patients with high-risk chronic lymphocytic leukemia (n = 22) and mantle-cell lymphoma (n = 13) received a total lymphoid irradiation of 80 cGy for 10 days and antithymocyte globulin 1.5 mg/kg/d for 5 days. Rituximab (375 mg/m(2)) was infused weekly on days 56, 63, 70, and 77 after transplantation. The incidence of acute GVHD was 6%. The cumulative incidence of cGVHD was 20%. Nonrelapse mortality was 3%. Rituximab treatment after allogeneic transplantation significantly reduced B-cell allogeneic immunity, with complete prevention of alloreactive H-Y Ab development in male patients with female donors (P = .01). Overall survival and freedom from progression at 4 years for chronic lymphocytic leukemia patients were 73% and 47%, respectively; for mantle-cell lymphoma patients, they were 69% and 53%, respectively.

• Authors: Sally Arai, Bita Sahaf, Balasubramanian Narasimhan, George L Chen, Carol D Jones, Robert Lowsky, Judith A Shizuru, Laura J Johnston, Ginna G Laport, Wen-Kai Weng, Jonathan E Benjamin, Joanna Schaenman, Janice Brown, Jessica Ramirez, James L Zehnder, Robert S Negrin, David B Miklos
• Journal: Blood (Blood) Vol. 119 Issue 25 Pg. 6145-54 (Jun 21 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22563089 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunosuppressive Agents
• Rituximab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, pharmacology)
• Autoimmunity (drug effects)
• B-Lymphocytes (drug effects, immunology)
• Chemoprevention (methods)
• Chronic Disease
• Drug Administration Schedule
• Feasibility Studies
• Female
• Graft vs Host Disease (epidemiology, immunology, prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immunosuppressive Agents (administration & dosage, pharmacology)
• Incidence
• Leukemia, Lymphocytic, Chronic, B-Cell (epidemiology, immunology, therapy)
• Male
• Middle Aged
• Pilot Projects
• Rituximab
• Transplantation Conditioning (methods)
• Transplantation, Homologous (adverse effects)
• Young Adult