New Treatment May Prolong Life for Heart Transplant Patients
Columbia Presbyterian Researchers Report Promising Results in Initial Study
Mar 2, 2000
Acute rejection is a primary cause of death in heart transplant recipients. A promising new treatment, daclizumab, under investigation at the Columbia Presbyterian Medical Center, has been shown to decrease the frequency of rejection without increasing the incidence of infection in heart transplant recipients for a three-month period following transplantation. Initial findings are reported in the March 2 issue of The New England Journal of Medicine.
Background and Major Points
Traditionally, post-operative transplant patients are treated with monoclonal or polyclonal antibodies to decrease frequency and severity of early organ rejection. Although these non-targeted therapies have been successful in delaying rejection, their side effects cause global immunosuppression in patients which, in turn, increases patients' risk for infection and cancer.
The primary mediator of solid organ rejection is the activated T-cell. Daclizumab is a humanized monoclonal antibody that can target specific arms of the immune system. It can bind to key receptors, such as Interleukin-2 on activated T-cells, without causing complete shutdown of the immune system. Previous studies with daclizumab among kidney transplant recipients have shown promising results—indicating decreases in number of allograft rejections and prolonged intervals without increases in the incidence of infection.
55 patients who were eligible for heart transplant at Columbia Presbyterian participated in the daclizumab study to test its safety and efficacy in reducing acute rejection frequency; 28 were administered daclizumab during post-operative cardiac biopsy, and 27 were not given daclizumab.
Acute rejection developed in 63 percent of the control group compared to only 18 percent in the daclizumab-treated group, and the time before onset of the first rejection episode was also significantly delayed in the latter group.
Furthermore, the severity of rejection was also reduced. Only two patients in the daclizumab-treated group developed moderately severe rejection compared to nine in the control group.
The first three months following transplantation are critical for recipients since it is during this period that they are more likely to experience frequent rejection episodes. Chronic rejection manifests as diffuse blockages along the entire length of the arteries of the new heart, a condition known as cardiac allograft vasculopathy, which is one of the main causes of death in transplant patients. Currently, no treatment exists to reverse this process once it develops; therefore, the focus of most strategies is to prevent its occurrence. There is evidence to suggest that reducing the number and the severity of acute rejections may have an impact on the development of chronic rejection.
Led by Dr. Ainat Beniaminovitz, Assistant Professor of Medicine and Assistant Attending Physician, the research team at Columbia Presbyterian concluded from their initial findings that daclizumab safely reduces the frequency and severity of allograft rejection in heart transplant patients, suggesting that this drug could significantly impact patients' long-term survival. Their results have led to plans for an expanded multicenter clinical investigation of daclizumab.