Gentler Immunosuppression

Drug Affords Gentler Immunosuppression in Children

May 9, 2007 (San Francisco) — Preconditioning with alemtuzumab (Campath-1H) can simplify the immunosuppression regimens needed for pediatric kidney transplant patients, Henkie P. Tan, MD, PhD, a professor of surgery at the University of Pittsburgh, in Pennsylvania, reported here. He also said that the approach might achieve a lower rejection rate with fewer complications than standard therapy.

Typically, kidney transplant patients receive tacrolimus (Prograf) and 2 other immunosuppressants, such as prednisone and mycophenolate (CellCept). This combination can cause severe adverse reactions, which are especially a concern in children.

“I think its groundbreaking work,” commented session moderator James J. Wynn, MD, of the Medical College of Georgia, in Augusta.

Alemtuzumab is a monoclonal antibody approved by the US Food and Drug Administration as a cancer treatment, but it has not yet been approved for immunosuppression. Dr. Tan and his colleagues presented previous data showing that preconditioning adult patients who receive kidney transplants with alemtuzumab allows them to rely on tacrolimus alone for immunosuppression. This approach has become the standard of care at their center, the Thomas E. Starzl Transplantation Institute, and more than 1000 patients have received transplants this way, Dr. Tan said. In the current study, the Starzl investigators set out to see whether the approach works in children.

Avoiding prednisone and other steroids is particularly important because they can interfere with children’s normal growth, said Dr. Tan. Reducing adverse reactions such as vomiting and diarrhea can help as well. “If you can use 1 agent as opposed to 3 agents, you will probably have better compliance,” Dr. Tan told Medscape.

In this study, Dr. Tan and his colleagues conditioned 24 unselected consecutive pediatric kidney patients with 0.4 to 0.5 mg/kg of alemtuzumab before transplantation. The kidneys were removed laparoscopically from living donors. After transplantation, the patients received tacrolimus to achieve a blood trough level of 10 ng/mL.

The mean recipient age was 9.0 ± 5.8 years, and the mean donor age was 36.3 ± 7.3 years.

The success of these transplants compared favorably to data from the United Network for Organ Sharing, Dr. Tan said. There was no incidence of delayed graft function. After a mean follow-up of 15.6 ± 10.3 months, all the patients and 96% of the grafts survived. The mean creatinine level at follow-up was 0.87 ± 0.43 mg/dL.

After 1 year, there was 1 episode of acute cellular rejection and, after 645 days, 1 renal allograft was lost because of vascular torsion of an intraperitoneal allograft.

The investigators gradually reduced the dose of tacrolimus in 12 of the patients, starting 306 ± 66 days after the transplantation. They cut the dose from twice to once per day, and then to 3 times a week, twice a week, and finally once a week with no acute cellular rejection. “At this level, the blood trough level is undetectable,” Dr. Tan told Medscape. “We just feel uncomfortable stopping the immunosuppression altogether.”

He said more research should be done to see whether patients can survive without any immunosuppression after being preconditioned with alemtuzumab.

Using less immunosuppression might also enable the patients’ immune systems to resist disease, Dr. Tan said. The patients in this study suffered no invasive cytomegalovirus infections, no posttransplant lymphoproliferative disease, and no BK viremia.

Dr. Wynn particularly admired the researchers’ approach to weaning their patients to such low doses of immunosuppressants. “Most of us are too chicken to try it,” he said.

The research was supported by the University of Pittsburgh. Neither Dr. Tan nor Dr. Wynn report any relevant financial relationships.

American Transplant Congress: Abstract 340. Presented May 7, 2007.