INCREASED INCIDENCE OF LYMPHOPROLIFERATIVE DISORDER AFTER IMMUNOSUPPRESSION WITH THE MONOCLONAL-ANTIBODY OKT3 IN CARDIAC-TRANSPLANT RECIPIENTS

A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation. In order to identify variables that predict the development of post-transplantation lymphoproliferative disorder, we analyzed retrospectively a series of 154 consecutive cardiac-transplant recipients at a single institution. Univariate analyses and multivariate analysis by logistic regression were performed. Among 75 patients who did not receive OKT3, post-transplantation lymphoproliferative disorder developed in 1 (1.3 percent), as compared with 9 of 79 patients who received the drug (11.4 percent); the incidence among the OKT3-treated patients was ninefold higher (odds ratio, 9.5; 95 percent confidence interval, 1.6 to 54.7). According to multivariate analysis, the only factor significantly associated with the development of post-transplantation lymphoproliferative disorder was the use of OKT3 (P = 0.001). A significant increase in risk with increasing doses was also apparent: 4 of 65 patients who received a cumulative dose of 75 mg of OKT3 or less (6.2 percent) had post-transplantation lymphoproliferative disorder, whereas 5 of 14 patients who received more than 75 mg had the disorder (35.7 percent; P<0.001). The addition of OKT3 to the immunosuppressive regimen increases the incidence of post-transplantation lymphoproliferative disorder after cardiac transplantation, and the risk increases sharply after cumulative doses greater than 75 mg. We suggest that the risks and benefits of prophylactic OKT3 administration be reassessed in the light of these findings, particularly since the value of prophylactic immunotherapy in cardiac-transplant recipients remains to be clearly established. POST-TRANSPLANTATION lymphoproliferative disorder is a well-recognized, frequently fatal complication of immunosuppression.1,2 The term encompasses a spectrum of abnormal proliferations of B lymphocytes that occur after organ transplantation. Such lymphoproliferative disorders have been identified in the wider context of immunodeficiency in general — whether it is congenital, due to human immunodeficiency virus type 1 (HIV), or associated with intensive chemotherapy for leukemia.3 4 5 The disease has provided insights into the nature of lymphoid cancer and has assumed increasing clinical importance in view of the HIV epidemic and the rising number of organ-transplant recipients. The incidence of post-transplantation lymphoproliferative disorder varies with the… © 1990, Massachusetts Medical Society. All rights reserved.