title: Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 less than 0.001).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Loyola University of Chicago, Maywood, Ill.
authors.forename: L J
authors.initials: LJ
authors.lastname: Swinnen
authors.forename: M R
authors.initials: MR
authors.lastname: Costanzo-Nordin
authors.forename: S G
authors.initials: SG
authors.lastname: Fisher
authors.forename: E J
authors.initials: EJ
authors.lastname: O'Sullivan
authors.forename: M R
authors.initials: MR
authors.lastname: Johnson
authors.forename: A L
authors.initials: AL
authors.lastname: Heroux
authors.forename: G J
authors.initials: GJ
authors.lastname: Dizikes
authors.forename: R
authors.initials: R
authors.lastname: Pifarre
authors.forename: R I
authors.initials: RI
authors.lastname: Fisher
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal