High fatality rate of Epstein-Barr virus-associated lymphoproliferative disorder occurring after bone marrow transplantation with rabbit antithymocyte globulin conditioning regimens

Abstract

Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (EBV-LPD) following bone marrow transplantation can be fatal. The major risk factors for the development of EBV-LPD are ex vivo T-cell depletion or in vivo T-cell depletion with either antithymocyte globulin (ATG) or monoclonal anti-T-cell antibodies. Between March 1999 and January 2001, a total of 23 transplants with ATG of equine source (20 transplants) and ATG of rabbit source (3 transplants) used as part of the preparatory regimen were performed at the Barbara Ann Karmanos Cancer Institute in Detroit, Mich. The three patients who received rabbit ATG developed EBV-LPD between 60 and 90 days following bone marrow transplantation. However, there were no cases of EBV-LPD in the equine group. Treatment given in these cases consisted of tapering immunosuppression, antiviral therapy, unprocessed donor lymphocyte infusion, mobilized peripheral blood progenitor cell rescue infusion (one patient), and chemotherapy (one patient). All three patients died of complications from EBV-LPD. The association of rabbit ATG with the development of EBV-LPD suggests that patients receiving rabbit ATG as part of their preparatory regimens require close monitoring of the EBV viral load and possible early intervention with antiviral therapy.

FIG. 1.

Histopathology of excised tissue from a patient with PTLD involving the liver, showing a large cellular infiltrate consisting of diffuse large immunoblasts with plasmacytoid features demonstrating EBV by use of immunohistochemical staining for EBER. Magnification, ×400.

FIG. 2.

Histopathology of excised tissue taken at autopsy from a patient with PTLD involving the liver, showing a large cellular infiltrate consisting of diffuse large immunoblasts with plasmacytoid features demonstrating EBV by use of immunohistochemical staining for EBER. Magnification, ×400.

FIG. 3.

Histopathology of excised tissue from a patient with PTLD involving the lymph node, showing a mixed infiltrate of lymphocytes and diffuse large immunoblasts with plasmacytoid features. Magnification, ×400.