[ Back to EurekAlert! ] Public release date: 8-Dec-2008
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center

New prognostic model for MDS covers all phases of disease

M. D. Anderson Cancer Center risk model applies beyond the newly diagnosed

IMAGE: Hagop Kantarjian, M.D., is chair of M. D. Anderson's department of leukemia.

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SAN FRANCISCO - A new risk model for myelodysplastic syndrome provides survival projections that apply to patients at any stage of the disease, researchers at The University of Texas M. D. Anderson Cancer Center report today at the 50th Annual Meeting of the American Society of Hematology.

"The previous prognostic model for MDS applies only to the newly diagnosed patient, so once therapy begins or the disease progresses, it cannot help guide our decisions," said study lead author Hagop Kantarjian, M.D., chair of M. D. Anderson's Department of Leukemia.

"Our new model, developed by analyzing 1,915 patients over 12 years, is applicable to any patient with MDS at any time during the course of the disease," Kantarjian said. The existing model, known as the International Prognostic Scoring System (IPSS), was developed at a time when there were few immediate treatment options for MDS.

Myelodysplastic syndrome comprises several conditions that cause insufficient production of blood cells, which are often lethal. About 10 percent of patients have their MDS transform into acute myelogenous leukemia, the least treatable form of adult leukemia.

The M. D. Anderson prognostic model adjusts for duration of the disease, prior therapy, development of secondary MDS and the presence of chronic myelomonocytic leukemia, in which white blood cells called myelomonocytes crowd out other blood cells. The model assigns points based on a combination of age, platelet count, anemia, percentage of cancerous cells, or blasts, in the bone marrow, and chromosomal abnormalities.

The new prognostic model stratified 958 study patients into four distinct prognostic groups with significantly different outcomes. Low-risk patients had a median survival of 54 months and 63 percent survived for three years, compared with 6 months and 4 percent for high-risk patients. Patients ranked at intermediate levels 1 and 2 fell between the two extremes. (See Chart)

Risk Score Number of patients (percent) Median survival in months 3-year survival percentage
Low 0-4 157 (16) 54 63
Intermediate 1 5-6 229 (24) 25 34
Intermediate 2 7-8 233 (24) 14 16
High ≥ 9 341 (36) 6 4

Results were validated in a separate test group of 957 patients. The model also was highly prognostic for 507 patients who were newly diagnosed, those to whom the IPSS model applies.

Kantarjian noted that the new model was prognostic when applied to the four IPSS risk groups, but the IPSS model was not prognostic when applied to the four risk groups in the new model. "In all aspects, the new model is a better one," Kantarjian said. "We are using it right now in the clinic."

In the past four years, therapy for MDS has improved significantly, with approval of three new drugs: lenalidomide, a thalidomide derivative indicated for some patients, and two demethylating agents that turn on genes by removing chemical "off switches" that block gene expression.

Previously, most patients were observed or received supportive care until MDS transformed into acute myelogenous leukemia. They then received supportive care such as blood transfusions and AML treatments that included relatively harsh chemotherapy or bone marrow transplants.

Researchers also applied the model to a three-arm clinical trial of the demethylating agent decitabine for MDS, where the model demonstrated improved survival with decitabine.

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Research was funded by a Physician-Scientist award from the Commonwealth Cancer Foundation for Research, a Leukemia and Lymphoma Translational Research Grant, and a grant from the National Cancer Institute.

Co-authors with Kantarjian and senior author Guillermo Garcia-Manero, M.D., who designed the study, are Susan O'Brien, M.D., Farhad Ravandi, M.D., Jorge Cortes, M.D., Jianqin Shan, Ph.D., all of M. D. Anderson's Department of Leukemia; John M. Bennett, M.D., of the University of Rochester in Rochester, N.Y., Alan F. List, M.D., of H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL, and Pierre Fenaux, M.D., Ph.D., of Hospital Avicenne in Bobigny, France.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For six of the past nine years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.



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