Abstract
The level of Epstein-Barr virus DNA in blood has proven to be a biomarker with some predictive value in allogeneic hematopoietic stem cell transplantation patients (HSCT). We evaluated the impact of EBV load on survival of 51 patients (32M/19F, median age: 32 years, from < 1 to 68 years old), who had received HSCT for different types of malignancies (49 cases) or non-malignancies (2 cases). The overall survival [1]was compared between patients with extreme and moderate cell bound EBV DNA levels. Different sources of stem-cells (peripheral blood stem, n = 39; bone marrow, n = 9; or umbilical cord blood, n = 3) were used. Twenty patients received reduced-intensity conditioning regimen while the other 31 received myeloablative conditioning. Patients with high or very low level of cell bound EBV-DNA levels had a shorter OS than those with moderate EBV load: OS at 5 years was 67% vs 90% (p < 0.03). There was a conspicuous relationship between EBV load and the reconstitution dynamics of total and EBV-specific T cells, CD4+ and CD4- CD8- (double negative) T cells in the few patients where it was analyzed. This was not statistically significant. Two other factors were associated to early mortality in addition to high or low EBV load: acute GVHD II-IV (p < 0.02) and pre-transplant conditioning with total body irradiation (TBI) ≥6 Gy, (p < 0.03). All the patients meeting all three criteria died within two years after transplantation. This points to a subgroup of HSCT patients which deserve special attention with improvement of future, personalized treatment.
Highlights
Patients receiving bone marrow (BMT) or hematologic stem cell transplants (HSCT) show a considerable risk to develop Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD) and lymphomas [1]
The following risk-factors have been associated with EBV-related complications after HSCT: HLA and EBV mismatch between recipient and donor, reduced intensity conditioning (RIC), acute graft-versushost disease (GVHD) and pre-transplant splenectomy [2]
The crucial role of T cell mediated immune response in controlling the EBV persistent infection is emphasized by the consistent observation that patients with T cell dysfunction are at high risk of developing EBV-associated lymphoproliferative conditions [23, 24]
Summary
Patients receiving bone marrow (BMT) or hematologic stem cell transplants (HSCT) show a considerable risk to develop EBV-associated posttransplant lymphoproliferative disorder (PTLD) and lymphomas [1]. The following risk-factors have been associated with EBV-related complications after HSCT: HLA and EBV mismatch between recipient and donor, reduced intensity conditioning (RIC), acute graft-versushost disease (GVHD) and pre-transplant splenectomy [2]. Imbalance in the control of the persistent, latent EBV-infection is one major factor in the pathogenesis of these complications. Epstein-Barr virus (EBV) is a gamma herpesvirus with the unique capacity to establish latent infection in human B lymphocytes and to activate them into proliferating lymphoblasts, acting thereby as a predisposing factor for different types of B-cell malignancies [5, 6]. In addition it has been demonstrated that helper CD4+ T lymphocytes can play an instrumental role in controlling the EBV-latency [10]
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