Sylvester Comprehensive Cancer Center

UM/Sylvester Cancer Scientist Develops a Screening Technique to Guide Treatment in Lymphoma Patients

04.29.2004

Izidore Lossos, M.D., a hematologist oncologist at the University of Miami Sylvester Comprehensive Cancer Center, is a lead author of a landmark lymphoma study published Thursday, April 29, in the New England Journal of Medicine. The study identifies six genes that can predict whether a person’s lymphoma will respond to standard treatment. This finding by researchers at the University of Miami School of Medicine, Stanford University School of Medicine, and Applied Biosystems, could result in the first gene-based screening to identify people who need aggressive therapy.

Large-B-cell, the most common lymphoma, accounts for between 30% and 40% of all lymphoma cases and 25,000 Americans are diagnosed each year. Currently, fewer than half those patients are cured.

Dr. Lossos, associate professor of clinical medicine at the UM School of Medicine and a member of the Leukemia, Lymphoma, and Myeloma site disease group at UM/Sylvester, and his colleagues, examined three previous gene studies of large-B-cell lymphoma. Researchers now use microarrays, which take a fingerprint of gene expression in different tissues, to find large groups of genes that predict a person’s survival. These studies have resulted in huge lists of genes that cannot be easily screened by most medical laboratories. Lossos and his colleagues narrowed the list of potential informative genes down to 36 then analyzed expression of those genes in diffuse large-B-cell lymphoma tumors. “Then we took the top six genes which predicted a positive outcome and did a multivariate analysis, comparing them in combinations,” said Lossos. “We found that there was a complex interrelation between all of them and that together they are highly predictive.”

This is not a new treatment for lymphoma, but it is a new screening test that may help guide treatment. About two-thirds of patients with this disease will benefit from standard chemotherapy and one-third will not. “Now we can identify which patients will have a bad outcome with standard treatment up front, and take these patients immediately into some investigational treatments or more aggressive treatments like bone marrow transplantation,” said Dr. Lossos. “We can improve their outcomes.”

“In leukemia we stratify patients for treatment based on their risk, which we can predict through chromosomal analysis,” said Lossos. “We did not have a reliable method for predicting outcomes in lymphoma, but now we do.”

To analyze expression of these genes, the investigators used a method called real-time polymerase chain reaction analysis (RT-PCR), which identifies and quantifies gene expression. “Real-time RT-PCR is highly reliable and can be used routinely in clinical laboratories,” Lossos said. This should make screening large-B-cell lymphoma patients relatively easy and affordable for other medical centers – which means it could become more readily available. Testing for expression of only six genes tremendously simplifies the ability to do this screening.

“This is really the first time we’ve used this technology to pinpoint a number of genes, but it can be done in other types of tumors,” said Lossos. “I predict that in five or six years we’ll have similar results in other tumors.”

“I think that if I were a patient today I would like to know what my outcome is, because if I learned through gene expression that I would respond to standard chemotherapy, I would opt for standard therapy,” said Lossos. “But if I knew I would not, I would seek something more aggressive from the beginning.”

The New England Journal study is available online: http://content.nejm.org/cgi/content/short/350/18/1828

UM/Sylvester was founded in 1992 to provide comprehensive cancer services and today serves as the hub for cancer-related research, diagnosis, and treatment at the University of Miami School of Medicine. UM/Sylvester handles more than 1,100 inpatient admissions annually, performs 2,800 surgical procedures, and treats 2,900 new cancer patients. UM/Sylvester physicians performed chemotherapy on more than 9,800 patients and radiation therapy on more than 4,400 patients from throughout the United States and Latin America. All UM/Sylvester physicians are on the faculty of the University of Miami School of Medicine, South Florida’s only academic medical center. In addition, UM/Sylvester physicians and scientists are engaged in more than 150 clinical trials and receive more than $30 million annually in research grants. UM/Sylvester at Deerfield Beach recently opened to better meet the needs of residents of Broward and Palm Beach Counties. This 10,000 square-foot facility at I-95 and S.W. 10th Street offers appointments with physicians from six cancer specialties, complementary therapies from the Courtelis Center, and education and outreach events.

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