Risk of lymphoid neoplasia after cardiothoracic transplantation - A cohortstudy of the relation to Epstein-Barr virus

Background Organ transplantation is associated with a greatly increased ris k of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD), which is often fatal. There has been little epidemiological analysis, howe ver, of the risk. factors for LPD in transplant patients and none on whethe r the risks of non-EBV-associated lymphoid neoplasms are also increased. Methods, The risk of lymphoid neoplasia was assessed in a cohort of 1563 pa tients who underwent cardiothoracic transplantation at Harefield Hospital, UK from 1980 to 1994 and were followed until December 1995. EBV antibody wa s assessed in the patients before transplantation, and lymphoid neoplasms w ere assessed for EBV RNA and latent EBV gene expression. Results. Thirty cases of LPD occurred during followup. One lymphoma of unkn own EBV status occurred. There were also six cases of EBV-negative non-Hodg kin's lymphoma (EBV-negative NHL), a highly significant excess over expecta tions from She general population rates of NHL (standardized incidence rati o 10.2 [95% confidence interval, 4.6-22.8]), The risk of LPD was significan tly 10-fold raised in individuals who were EBV seronegative before transpla ntation; independently of this, it decreased steeply with age at transplant ation and was greatest in the first year after transplantation. The risk wa s significantly raised in young seronegative recipients if the donor was ol der than the recipient. EBV-negative NHL occurred entirely in men 45 years old and older who were EBV seropositive before transplantation, and risk wa s not related to duration since transplantation. Conclusions. The risk factors found for LPD accord with EBV etiology and wi th greater hazard from primary infection than from reactivation. A second n on-Hodgkin's lymphoid neoplasm, not related to EBV, seems also to be a cons equence of transplantation and immunosuppression but is unlikely to be due to first infection by a ubiquitous agent. Its etiology and prevention need investigation separately from LPD.