ABSTRACT
Chronic graft-versus-host disease is the major long-term complication after allogeneic stem cell transplantation with a suboptimal response rate to current treatments. Therefore, clinical efficacy and changes in lymphocyte subsets before and after rituximab treatment were evaluated in a prospective phase II study in patients with steroid-refractory chronic graft-versus-host disease. Overall response rate was 61%. Only responding patients were found to have increased B-cell numbers prior to treatment. B cells had a naïve-antigen-presenting phenotype and were mainly CD5 negative or had a low CD5 expression. Normal B-cell homeostasis was reestablished in responding patients one year after ritxumab treatment and associated with a significant decline in skin-infiltrating CD8(+) T cells, suggesting that host B cells play a role in maintaining pathological CD8(+) T-cell responses. Imbalances in B-cell homeostasis could be used to identify patients a priori with a higher chance of response to rituximab treatment (Eudra-CT 2008-004125-42).
Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Graft vs Host Disease/drug therapy , Graft vs Host Disease/immunology , Immunophenotyping , Immunosuppressive Agents/therapeutic use , Antibodies, Monoclonal, Murine-Derived/administration & dosage , B-Lymphocytes/immunology , Chronic Disease , Graft vs Host Disease/etiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Lymphocyte Depletion , Phenotype , Prognosis , Rituximab , Transplantation, Homologous , Treatment OutcomeABSTRACT
We investigated the role of donor cytomegalovirus (CMV) serostatus on reactivation of CMV infection in CMV-infected transplant recipients. Reactivation of CMV infection occurred more frequently in patients receiving a CMV-positive graft but was less severe than in patients receiving a CMV-negative graft. These data suggest roles for both virus as well as CMV-specific immunity present in the graft.
Subject(s)
Cytomegalovirus Infections/pathology , Cytomegalovirus/isolation & purification , Severity of Illness Index , Stem Cell Transplantation , Tissue Donors , Virus Activation , Cytomegalovirus/immunology , Cytomegalovirus Infections/immunology , Female , Humans , Incidence , Male , Middle AgedABSTRACT
Chronic graft-versus-host-disease (cGVHD) is the major cause of late morbidity and mortality after allogeneic stem cell transplantation. B cells have been reported to be involved in mediating cGVHD. To assess whether preemptive host B cell depletion prevents extensive cGVHD after allogeneic reduced-intensity conditioning transplantation (RICT), 173 patients treated with RICT for various hematologic diseases, who had or had not received Rituximab (Rtx) within 6 month prior to RICT, were analyzed retrospectively. Rtx treatment within 6 months prior to RICT reduced extensive cGVHD significantly from 45.8% to 20.1%. We hypothesize that most likely host B cells initiate cGVHD, and thus, host B cell depletion prior to RICT by Rtx might be a valuable strategy to reduce extensive cGVHD after RICT.
Subject(s)
Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/drug effects , Graft vs Host Disease/prevention & control , Hematologic Diseases/surgery , Lymphocyte Depletion/methods , Transplantation Conditioning/methods , Adult , Aged , Alemtuzumab , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antibodies, Monoclonal, Murine-Derived , Antibodies, Neoplasm/therapeutic use , Antilymphocyte Serum/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Lymphocytes/immunology , Chronic Disease , Combined Modality Therapy , Disease-Free Survival , Drug Administration Schedule , Female , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Hematologic Diseases/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Patient Selection , Premedication , Retrospective Studies , Rituximab , Sample Size , Young AdultABSTRACT
After infection with the Epstein - Barr virus, a common gammaherpes virus which infects and persists in the B cells, an equilibrium is established in which newly infected and differentiating B cells are controlled by cytotoxic T cell (CTL) responses. Disturbance of this equilibrium, which can occur in immunocompromised situations, can lead to uncontrolled lymphoproliferation and subsequent development of non-Hodgkin Lymphomas (NHL). Here, we review the role of immunesurveillance of EBV-infected B cells and two situations where immunesurveillance is altered because of immunodeficiencies, transplantation recipients and HIV infection, which can lead to EBV-mediated NHL. In transplant recipients, immunosuppression prior and during transplantation can lead to lack of immunesurveillance and results in proliferation of infected B cells, which would normally be controlled by CTL responses. Interestingly, in HIV infection both deregulation of the normal B cell biology and a reduction in immunity play a role in developing NHL. Therefore, the nature of EBV infection in HIV-positive subjects is very different from that in transplanted individuals, in whom (re-)appearance of EBV-specific CD8(+) T cells - either by a decrease in immune suppression or infusion of donor lymphocytes - immediately leads to a decrease in EBV load.
