Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients

Article Abstract:

To a great degree, the success of organ transplantation procedures has resulted from improvements in methods of immunosuppression, which reduce the likelihood that the recipient's immune system will reject the new organ. However, this necessary immunosuppression is not without its own potential complications. Like the immunosuppression due to chemotherapy and that due to AIDS, the immunosuppression for transplantation may result in infection and lymphoproliferative disorder. The lymphoproliferative disorder, which can be life-threatening, is thought to result from primary or reactivated infection with the Epstein-Barr virus. An increase in the incidence of lymphoproliferative disorder was recently observed in a series of heart transplant patients at one institution. Researchers noticed that the increase seemed to occur at the same time that a new method of improving immunosuppression was introduced. A retrospective study of 154 heart-transplant patients was then undertaken to determine if this treatment was, indeed, responsible for the increase in lymphoproliferative disorder. The new treatment was the use of the drug OKT3 for immunosuppression. OKT3 is a monoclonal antibody which binds to the CD3 receptor on T cells. In humans, treatment with OKT3 results in a depletion of circulating T cells with the CD3-positive lymphocytes. Previously, OKT3 had been reserved as treatment for those cases in which conventional immunosuppression was failing, but recently it has come to be used prophylactically for all transplant patients at some medical centers. The review of the patient records revealed that post-transplantation lymphoproliferative disorders developed in 1 of 75 patients (1.3 percent) who did not receive OKT3, and in 9 of 79 patients (11.4 percent) who did get the monoclonal antibody. Statistical analysis showed that the OKT3 antibody was the only variable which was significantly associated with the development of lymphoproliferative disorder in these patients. Since the value of OKT3 as a prophylactic agent in transplant patients has not been clearly established, the risks must be carefully considered before the treatment is prescribed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Lymphoproliferative disorders, Immunoproliferative disorders

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Preemptive therapy in immunocompromised hosts

Article Abstract:

One of the greatest success stories in biomedical science in the 20th century was the development of organ and bone marrow transplants. Although transplants can save lives there are complications associated with the procedure. The two major concerns following a transplant are the survival of the patient and of the donor organ. It is the function of the immune system to recognize the body's own tissues and to destroy foreign substances, or in this case, donor tissue. Therefore, recipients of organ transplants are treated with drugs, such as cyclosporine, to suppress the immune system so that it will not attack and destroy the transplanted organ. However, such drugs make a patient susceptible to opportunistic infections that can be life-threatening. One particular example is the case of cytomegalovirus infection and the subsequent development of pneumonia in patients receiving bone marrow transplants. In these patients, pneumonia caused by cytomegalovirus infection ends in death for over 80 percent of the cases. In the past, all bone marrow recipients were treated with antimicrobial agents (acyclovir and immunoglobulin) as a preventive measure against the development of infection. However, this procedure is costly and it exposes uninfected patients to the risks and potential toxic effects associated with the drug treatments. Recently, a new strategy for treating cytomegalovirus infection in bone marrow transplant patients was developed. The procedure involves using laboratory tests to identify patients with cytomegalovirus infection prior to the development of symptoms, and those with infection are treated with the antiviral drug ganciclovir. The proven effectiveness of this procedure has been demonstrated in a recent clinical trail, the results of which are reported in the April 11, 1991 issue of the New England Journal of Medicine. This type of treatment strategy, namely diagnostic testing followed by treatment of those who are infected, can be used as a model to design treatments for other infectious diseases that occur in transplant patients or in other patients with suppressed immune systems. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Drug therapy, Cytomegalovirus infections, Bone marrow, Bone marrow transplantation

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Cancers complicating organ transplantation

Article Abstract:

The successful transplantation of organs requires suppression of the immune system, which would otherwise reject the foreign tissue; medications are used to inhibit the immune system. However, this immunosuppression causes problems of its own. Since the late 1960s, it has been clear that organ transplant recipients are more likely to get some types of cancer. Overall, 6 percent of transplant recipients develop cancer, but only 1 percent die from it. The cancers which are increased in likelihood among these patients do not reflect the cancers which are most common in the population as a whole, but are rather cancers which are relatively uncommon in the general population. These include lymphomas, squamous cell carcinoma of the lips and skin, Kaposi's sarcoma, carcinomas of the vulva and perineum, carcinomas of the kidney, and hepatobiliary tumors, in addition to others. Even among lymphomas, the cancers are different in the transplant recipients than in the general population. While about 65 percent of lymphomas are non-Hodgkin's lymphomas in the general population, 93 percent are the non-Hodgkin's type among the transplant patients. Furthermore, the natural history of the lymphomas is different; about 1 percent of non-Hodgkin's lymphomas involve the brain in the general population, in contrast to about 28 percent among transplant patients. In the December 20, 1990 issue of The New England Journal of Medicine, researchers report how a new method of improving immunosuppression, the use of antibodies to deplete T cells (known as OKT3), resulted in a higher incidence of lymphoproliferative disorder as an unwanted side effect. These findings should not be viewed as a reason to back away from transplantation, which is a life-saving therapeutic option for many patients. However, it is clear that greater understanding must be reached regarding the functioning of the immune system and the manner in which immunosuppression promotes and alters the development of particular tumors. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cancer

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