Effect of cytomegalovirus prophylaxis with immunoglobulin or with antiviral drugs on post-transplant non-Hodgkin lymphoma: a multicentre retrospective analysis

BACKGROUND: Post-transplant non-Hodgkin lymphoma is a feared complication of immunosuppressive treatment and is associated with high mortality. Most post-transplant lymphomas develop from the uncontrolled proliferation of Epstein-Barr-virus (EBV)-infected B lymphocytes. No reliable methods for the prevention of EBV infection and lymphoma are available. We aimed to elucidate the effect of prophylactic treatment for cytomegalovirus (CMV) infection on the incidence of post-transplant lymphomas. METHODS: In a multicentre retrospective study, we analysed the incidence of post-transplant non-Hodgkin lymphoma in 44 828 recipients of deceased-donor kidney transplants who were reported to the scientific registry of the Collaborative Transplant Study. Patients had received antiviral drugs (aciclovir or ganciclovir) or anti-CMV immunoglobulin to prevent CMV infection according to the transplant centres' protocols, or no CMV prophylaxis. Standardised incidence ratios (SIR) of lymphoma were calculated and compared by chi(2) analyses FINDINGS: During the first post-transplantation year, 30 255 patients who did not receive CMV prophylaxis developed lymphomas at SIR 26.4. Lymphoma incidence in 12 470 patients who received antiviral treatment was nearly identical (SIR 24.2, p=0.62) to that in patients who did not receive CMV prophylaxis. However, 2103 patients who received anti-CMV immunoglobulin showed a complete absence of lymphomas in the first after-transplantation year (SIR 0; p=0.012 vs no treatment, p=0.016 vs antivirals). In the subsequent 5 years of follow-up, new cases of lymphoma developed at similar rates in all three groups (p=0.97). INTERPRETATION: These findings suggest that prophylactic anti-CMV immunoglobulin prevents the development of early post-transplant non-Hodgkin lymphoma in kidney-graft recipients. Prophylactic treatment with antiviral drugs does not reduce the risk of post-transplant lymphoma.