Increased Incidence of Lymphoproliferative Disorder after Immunosuppression with the Monoclonal Antibody OKT3 in Cardiac-Transplant Recipients

Abstract

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.

Lymphomas After Solid Organ Transplantation: A Collaborative Transplant Study Report

“…The use of potent antilymphocyte antibodies, particularly OKT3, for prophylaxis of acute rejection after solid organ transplantation is associated with a higher risk for lymphoma (6,12). In the present analysis of cadaver kidney recipients, a three to fourfold higher risk for lymphoma posed by both ATG and OKT3 was evident early after transplantation.…”

“…Caution has been advocated for use of multidrug combinations of powerful immunosuppressants (12,37). In heart transplantation, this warning has led to reduced use of OKT3 in recent years (from 13.9% between 1985 and 1989 to 6.2% in the 1995-2001 period) and likely to reductions in dosage and duration of treatment.…”

“…Experience with FK506-based immunosuppression is limited, although an increase in lymphomas has been described among pediatric patients (10,11). A heightened risk for lymphoma has also been reported among patients receiving induction therapy with OKT3, especially beyond a threshold cumulative dose (6,9,12). It has been speculated that the intensity of immunosuppression, rather than any individual agent, is a key determinant of lymphoma formation (13,14), a conclusion supported by the higher incidence of lymphoma in recipients of nonrenal transplants, who receive higher doses of immunosuppression (6,15).…”

The non-Hodgkin lymphomas: A review of the epidemiologic literature

“…Positive associations have been reported in studies that examined the use of immunosuppressive drugs after organ transplantation. [651][652][653] In a study evaluating the risk factors for mycosis fungoides, no associations were found with past or present use of hypnotics, diuretics, corticosteroids or NSAIDs. 654 …”

“…652,653,[667][668][669][670][671][672][673] Kinlen et al 668 in a preliminary report of a multi-center study of patients who received immunosuppressive therapy, reported 34 observed NHL cases (0.58 expected) among renal transplant recipients. Following renal transplantation, a significantly increased risk of NHL among men (SIR 5 10.0, 95% CI: 5.8-16.0) and women (11.0, 95% CI: 4.8-20.0) was reported in a cohort study in the Nordic countries.…”