Epstein-Barr virus lymphoproliferation after bone marrow transplantation

Abstract

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.

Risk factors for post‐transplant lymphoproliferative disorder after Thymoglobulin‐conditioned hematopoietic cell transplantation

“…Our study provided the following important findings: after HCT are of donor origin. 28,29 Regarding the importance of the recipient anti-EBV immunity, it has been documented for CMV that recipient anti-CMV T cells persist early post-transplant and protect the patients from CMV disease. 30 This also applies to recipient antiadenovirus T cells.…”

Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

“…Recent data implicated that CMV and HHV-6 might contribute to the development of PTLD [90,91]. The incidence of PTLD varies from 0.5% to 22%, depending on the number of risk factors [3,68,[92][93][94]. In the recipients of allo-HSCT, most of PTLD occur within 1 year post-transplantation, reaching a peak incidence within 3 months [95][96][97].…”

Establishment of anti-Epstein–Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection

“…Virus-induced transformation of infected cells is associated with various malignant diseases [3][4][5][6]. EBV-associated lymphoproliferative disease has been observed in patients with X-linked lymphoproliferative disease [7] and those receiving intensive immunosuppressive therapy, such as bone marrow transplantation [8][9][10].…”