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.

Outcome of treatment of Epstein–Barr virus‐related post‐transplant lymphoproliferative disorder in hematopoietic stem cell recipients: a comprehensive review of reported cases

“…The role of EBV in contributing to lymphomagenesis is especially well established in the lymphoproliferative diseases that arise in immunosuppressed individuals (68–70). In patients treated with allogeneic HSCT, the incidence of EBV‐PTLD varies from 0.45% to 29%, according to the source of hematopoietic cells, the associated cell manipulation, and the details of immunosuppressive regimens used (1, 71, 72). In recipients of solid organ transplants, the incidence of PTLD ranges from 1% to 15% (73, 74).…”

EBV PCR in the Diagnosis and Monitoring of Posttransplant Lymphoproliferative Disorder: Results of a Two-Arm Prospective Trial

“…Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of pharmacologic immunosuppression used routinely in solid organ and stem‐cell transplant patients. Up to 15% of transplant patients develop PTLD with a mortality rate of 40–70% (1–6). PTLD is often detected at a late stage when patients have a poor performance status and are suffering from side effects of their lymphoma.…”

“…Early diagnosis of PTLD is important, as it expands treatment options to include reduction in immunosuppression, rituximab, or chemotherapy. In addition, patients with early stage disease are better able to withstand therapy and have the highest chance for cure (5,7).…”

Prognostic factors and outcome of Epstein–Barr virus DNAemia in high‐risk recipients of allogeneic stem cell transplantation treated with preemptive rituximab

“…Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of developing post‐transplant lymphoproliferative disorder (PTLD), which presents clinically as aggressive and frequently fatal lymphomas . The overall frequency is approximately 1% ; however, it varies from 0.45% after HSCT from matched family donors to 11.7–29% after HSCT from T‐cell–depleted unrelated donors . The highest incidence occurs in the first 6 months after transplant, and the vast majority of cases develop during the first year .…”