Is autologous graft versus host disease (AutoGVHD) really reactivation of Epstein-Barr virus (EBV)?

Abstract

17526 Background: AutoGVHD is a rare complication following autologous bone marrow transplantation(ABMT). It has been described as an autoimmune syndrome initiated by auto-effector T cells that recognize self-major histocompatibility complex class II antigens. AutoGVHD can be induced with immunosuppresives such as cyclosporine and alemtuzumab. Methods: We wish to report two patients among 17 patients who underwent ABMT this year of what was intially thought to be AutoGVHD but in both instances was really reactivation of EBV. Results: A 70 year old white man underwent ABMT for relapsed AML M2 in second CR. The conditioning regimen was cyclophosphamide and busulfan (BuCy). His hospital was uneventful and the prophylatic antibiotics used were ciprofloxacin, fluconazole, and valacyclovir. Neutropenic fever occured on day +11 and prophylatic antibiotics were discontinued and replaced with intravenous vancomycin, piperacillin&tazobactam, and caspofugin. Engraftment occured on day +15 and the patient was discharged on day + 20 on oral valacyclovir and fluconazole. An AutoGVHD rash occurred on day+29. The second patient was a 67 year old white with a stage IIIAE mantle cell lynphoma who underwent ABMT in first CR with the BEAM+rituximab regimen. His hospital course was uneventful; he received the identical prophylatic antibiotic regimen. Engraftment occured on day +12 and he was discharged on valacyclovir and fluconazole. On day +14 he developed an AutoGVHD rash. The first patient underwent a skin biopsy which showed a spongiotic dermatitis with intraepithelial vesicular formation and dermal perivascular lymphocytes. The immunostains of the lymphocytes showed a predominance of CD4 T cells. Immunostains for CMV, EBV, HSV1 and 2 were nonreactive. Serum antibodies to the Early EBV antigen and EBV capsid (IgG) and EBV nuclear (IgG) were elevated. Serologies for Human Herpes Virus 6, 7, and 8 were negative. The second patient had elevated antibodies to the Early EBV antigen, EBV capsid antigen, and the EBV nuclear antigen. He had elevated antibodies to Human Herpes Virus 6. Conclusions: These two patient suggests that what clinically is thought to be AutoGVHD may indeed be reactivation of EBV. The incidence of reactivation of EVB in ABMT needs to be studied prospectively. No significant financial relationships to disclose.