Public Release: 

New approach to post-transplant lymphoma shows promise

Ohio State University Wexner Medical Center

COLUMBUS, Ohio - Scientists may be making significant headway in treating one of the most difficult and often fatal complications of organ transplant, PTLD, or post-transplant lymphoproliferative disorder.

PTLD is a form of lymphoma, or cancer of the glands of the lymph system, associated with the presence of the Epstein-Barr virus (EBV). Normally, EBV itself is not threatening - scientists say 90-95 percent of us carry it in our systems all the time. But it poses special problems for transplant patients because the drugs they have to take to keep their body from rejecting new organs weaken the immune system and create the perfect environment for the virus to spring into action.

Kidney transplants are among the most common transplants in the United States, with more than 10,000 renal transplants performed annually for patients with end-stage renal disease. PTLD occurs in 1 to 2 percent of kidney transplants, with mortality ranging from 50 to 70 percent. PTLD may develop following kidney or other organ transplants when EBV-infected B lymphocytes proliferate uncontrollably in the absence of the infection-fighting immune cells that normally keep them in check.

It's a tricky complication to treat successfully.

A multidisciplinary team of physicians and scientists at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute - Ohio State University Comprehensive Cancer Center, however, says it has had significant success treating PTLD using a two-part therapy that includes the use of the antiviral drug acyclovir along with gradual reductions in patients' immunosuppressive drugs. By reducing the doses of the drugs that suppress the rejection of the transplanted organ and the function of the normal immune system, the immune mediators that recognize and kill EBV-infected cancer cells are allowed to do their job.

Drs. Pierluigi Porcu and Charles Eisenbeis, oncologists at The James, used the approach with 11 consecutive kidney transplant patients who developed PTLD eight to 94 months after transplant. All of the patients developed diffuse large B-cell lymphomas.

Following treatment, 10 of 11 patients had a complete response, meaning all evidence of the disease disappeared, and nine of 11 patients ( 82 percent of those treated) maintained the response with a median follow-up of almost two and one-half years. Patients who recovered had stronger immune systems, measured by increases in the numbers of their T cells, suggesting the therapy stimulated the specific cells needed to destroy the lymphoma.

The study appears in the online version of the journal Blood at http://www.bloodjournal.org/cgi/reprint/2002-01-0210v1.pdf.

Previous approaches to treating PTLD included chemotherapy to kill the lymphoma cells, the use of antiviral agents to disable the EBV, or monoclonal antibody therapy designed to impact changes in the blood's B cells. Each therapy has its drawbacks, with optimal therapy remaining elusive.

Porcu says this is the first prospective analysis of a uniform approach to treating kidney transplant patients who develop PTLD with antiviral therapy plus graduated reduction in immunosuppression.

"These results appear promising for what is often a fatal disease," says Porcu, noting previously described treatments have been only half as effective, generating a complete response rate of only 50 percent.

Porcu says the therapy has some limitations, noting that kidney rejection did occur in those patients with PTLD in the transplanted organ.

"Still, the survival results from a potentially fatal malignancy are striking and those patients losing the kidney graft should ultimately be eligible for a second transplant," he added.

A large team of physicians and scientists gave early support and direction to the study, including Dr. Ronald Ferguson, professor of surgery and chief of transplantation and his team of transplant surgeons, pathologists Gerald Nuovo and William Marsh and the laboratory staff of Dr. Michael Caligiuri, director of the Division of Hematology/Oncology at Ohio State and associate director for clinical research at the OSUCCC.

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