© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 20, 1519,
October 17, 2001
© 2001 Oxford University Press
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Rapamycin May Prevent Post-Transplant Lymphoma
Non-Hodgkin’s lymphoma is a dreaded complication of organ transplantation. For kidney transplant patients, the risk of lymphoma is 37 times higher than for the general population in the first year after surgery, and for heart transplant patients, it is 155 times higher. Lymphoma is so common after transplants that a new disease term, Post-Transplant Lymphoproliferative Disorder (PTLD), was coined to describe these virulent cancers, of which about 70% prove fatal despite treatment—most within 1 year of diagnosis.
The cause of PTLD is thought to be drug-induced immunosuppression, which allows activation of latent Epstein-Barr virus, which immortalizes infected B cells and sets the stage for malignancy. The widely used immunosuppressants cyclosporine and FK506 are especially dangerous. But rapamycin, an immunosuppressant approved in 1999 by the FDA for kidney transplantation, might help reverse the PTLD scourge.
At the joint annual meeting of the American Society of Transplantation and the American Society of Transplant Surgeons last May, Manikkam Suthanthiran, M.D., of Cornell University, reported that cyclosporine and FK506 increased the number of metastases in several mouse models of organ transplantation, but that rapamycin blocked metastases. "If that observation holds up statistically, I think it will argue very much in favor of more broad use of rapamycin in the transplant setting," said Jay Gibbons, Ph.D., assistant vice president for oncology research for Wyeth-Ayerst, which markets rapamycin. "That’s a clear-cut advantage."
Rapamycin is newly approved, so it will be many years before the drug’s PTLD-preventive effect (if any) becomes clear. But the National Cancer Institute is sponsoring a phase II lymphoma treatment trial of the rapamycin analogue CCI-779 (see main story). Success would imply that rapamycin indeed can prevent the devastation of PTLD.
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