Rapid reconstitution of CD4 T cells and NK cells protects against CMV-reactivation after allogeneic stem cell transplantation.

Background: Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT).

Methods: Here we investigated the role of immune cell reconstitution in the onset and subsequent severity of EBV- and CMV-reactivation. To this end, 116 patients were prospectively sampled for absolute T cell (CD4 and CD8), B-cell (CD19) and NK-cell (CD16 and CD56) numbers weekly post-SCT during the first 3 months and thereafter monthly until 6 months post-SCT.

γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia.

Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV reactivation after allo-SCT and reduced leukemic relapse. Given the potential of Vδ2-negative γδT cells to recognize CMV-infected cells and tumor cells, the molecular biology of distinct γδT-cell subsets expanding during CMV reactivation after allo-SCT was investigated.

Adequate control of primary EBV infection and subsequent reactivations after cardiac transplantation in an EBV seronegative patient.

EBV seronegative recipients of cardiac transplantation are at risk for development of post transplant lymphoproliferative disease following primary EBV infection due to the ongoing treatment with immunosuppressive drugs. Here we present detailed kinetics of the EBV-specific T-cell response following cardiac transplantation in an EBV seronegative recipient who developed a primary EBV infection 15weeks post transplantation and subsequent viral reactivations throughout follow up. The patient developed an EBV-specific CD8(+) T-cell response within 24days after first detection of the primary infection.

The immunological phenotype of rituximab-sensitive chronic graft-versus-host disease: a phase II study.

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%.

Influence of donor cytomegalovirus (CMV) status on severity of viral reactivation after allogeneic stem cell transplantation in CMV-seropositive recipients.

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.

High level of perforin expression in T cells: An early prognostic marker of the severity of herpesvirus reactivation after allogeneic stem cell transplantation in adults.

Background: Epstein-Barr virus (EBV) and cytomegalovirus reactivations are frequent complications of hematopoeitic allogeneic stem cell transplantation (SCT) because of a lack of T cell control after immunosuppression. Early diagnosis of reactivation and subsequent preemptive therapy relies on frequent viral load measurement. Additional virus-specific T cell reconstitution data could improve the predictive value of viral load detection for viral complications after transplantation.

Rituximab treatment before reduced-intensity conditioning transplantation associates with a decreased incidence of extensive chronic GVHD.

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.

Immune surveillance of EBV-infected B cells and the development of non-Hodgkin lymphomas in immunocompromised patients.

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.