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LOS ANGELES (April 20, 1999) -- A potentially catastrophic complication of transplantation that affects 10 to 15 percent of children who receive livers or other donated organs can now be detected and treated early.
Using a method of periodic testing devised by researchers at Cedars-Sinai Medical Center, physicians can monitor the progress of young transplant recipients to rapidly detect virally infected cells. With this information, they can quickly intervene in an effort to prevent progression to posttransplant lymphoproliferative disorder (PTLD), a type of cancer with an estimated mortality rate ranging from 40 to 70 percent of the children who develop it. Most of those who survive must endure long-term complications.
"We think the way this disorder works is that patients, especially pediatric patients who have not been exposed to the Epstein-Barr virus, have the virus transmitted to them when they receive the organs of adults," said Stanley C. Jordan, M.D., director of Pediatric Nephrology and Transplant Immunology, and medical director of the Renal Transplant Program at Cedars-Sinai. "The virus is often dormant in tissues but when we suppress the immune systems of patients, the virus starts to replicate. It can affect the immune cells, primarily B cells, of the recipient. Because the patient is immune-suppressed, they can't get rid of the virus. This eventually causes a malignant transformation of the cells."
Transplant specialists, using a variety of medications, intentionally suppress the immune system of a transplant recipient to prevent rejection of a new organ. One possible consequence of this immune suppression, however, is the patient's susceptibility to other invading organisms, in this case the Epstein-Barr virus. Dr. Jordan said common symptoms of PTLD include enlarged lymph nodes, swollen liver, spleen and other organs, and gastrointestinal bleeding. Once a patient becomes symptomatic, however, the disorder may have advanced too far to be reversed.
Instead of waiting and watching for symptoms to begin, transplant specialists who use the blood test report that its early warning could "potentially eliminate this disorder," Dr. Jordan said. "Using this quantitative test, we look for evidence of Epstein-Barr virus replication. Normally, we do not see any virus in a patient's blood unless they're actively transcribing (reproducing) the virus. If we have baseline values that are negative or very low and we see replication of the virus start, we can institute treatment before extensive organ damage is done." Dr. Jordan and his team feel this test has great potential for early detection and treatment of PTLD, but more experience is needed to prove effectiveness.
Treatment usually includes a reduction in medications that suppress immune response, along with the introduction of antiviral drugs and those that support the immune system, such as intravenous immunoglobulin (IVIG) therapy.
Patients who will develop PTLD - a complication that affects less than one percent of adult transplant recipients - generally do so within six to 12 months of transplantation.
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