Transplantation
Combination Therapy Shows Significant Anti-rejection Benefits in Heart Transplants
By University of California, Los Angeles
May 24, 2005, 10:43

Amid the debate over which combination of immunosuppressive agents works best in helping patients fight off rejection of their new heart after transplant surgery, a new study led by researchers at the UCLA Heart Transplant Program showed that one particular combination using tacrolimus (TAC, or Prograf) had significant anti-rejection benefits for heart transplant patients over other combinations.

A mix of immunosuppressive therapies typically is used to prevent a recipient's body from rejecting a transplanted organ. Rejection is one of the most common causes of death in the first year after heart transplantation.

"Until now, there has been a lack of definitive clinical trial data comparing commonly used immunosuppressive agents, and this has caused some debate over what is the most advantageous combination of therapies for heart transplant recipients," said Dr. Jon Kobashigawa, lead author of the study and medical director of the UCLA Heart Transplant Program. "We now have results that demonstrate benefits in treating non-cellular and humoral rejection and this is a significant step forward for heart transplant patients."

The study results, presented at the 6th American Transplant Congress in Seattle, involved more than 340 heart transplant recipients, and evaluated three combination therapies: 1) TAC plus mycophenolate mofetil (MMF) and steroids, 2) cyclosporine microemulsion (CYA) plus MMF and steroids, and 3) TAC plus sirolimus (SRL) and steroids.

The primary purpose of this study was to compare the incidence of rejection requiring treatment, as measured by the International Society for Heart and Lung Transplantation grading system.

Humoral rejection recently has been described in liver, kidney and heart transplant recipients by the National Institutes of Health Consensus Conference. Humoral rejection is caused by the body making antibodies that can attack the donor organ, which is similar to the way that antibodies attack other foreign objects such as viruses or other infectious agents. This form of rejection can occur immediately (hyperacute rejection), or later after transplantation. The antibodies are either preformed antibodies (causing hyperacute rejection) or represent antibodies against the donor organ that developed after transplantation.

In heart transplant recipients, humoral rejection has been reported to play a role in the donor heart becoming weak in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease, which is one of the major factors limiting long-term survival.

The study found no significant differences between treatment groups in survival or incidence of treated cellular rejection. Importantly, there was a significant reduction in any treated rejection in the TAC-treated groups. The category of any treated rejection included both cellular and humoral rejection. Therefore, these results suggested less humoral rejection in the TAC-treated groups.

The study also found that the TAC/MMF group had significantly better kidney function and lower triglycerides levels compared to the other two groups. Rates of post-transplant diabetes were not significantly different. Fewer viral infections, but more fungal infections, were found in the TAC/SRL group.

The authors concluded that in heart transplant patients, TAC/MMF appeared to offer more advantages than either TAC/SRL or CYA/MMF, including the lowest incidence of any treated rejection and an improved side-effect profile.

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