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

Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.

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.

Trial registration: ClinicalTrials.gov NCT00186628.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00186628