Scoring system identifies MDS patients who have low-risk disease but a poor prognosis

December 21, 2007

HOUSTON - A new scoring system for a form of leukemia known as myelodysplastic syndrome (MDS) identifies patients who appear to have low-risk disease but actually have poor prospects of survival, researchers at The University of Texas M. D. Anderson Cancer Center report online at the journal Leukemia.

"We know an undefined group of MDS patients who are classified as low-risk by our present prognostic models will at some point have a sudden worsening of their disease. Right now, we don't know who these people are, but if we can identify them, we can start those with a poor prognosis on early treatment," says lead author Guillermo Garcia-Manero, M.D., associate professor in M. D. Anderson's Department of Leukemia.

Physicians tend to adopt a watch and wait approach to low-risk MDS patients, which Garcia-Manero says misses low-risk/poor prognosis patients. Myelodysplastic Syndromes are a group of conditions that cause insufficient production of blood cells, which is often lethal. About 10 percent of patients have their MDS transform into acute myelogenous leukemia.

Garcia-Manero and colleagues examined a number of potential molecular and demographic markers to develop a prognostic scoring system for this group by applying them to 856 patients treated at M. D. Anderson between 1976 and 2005. All were rated low or intermediate risk by the International Prognostic Scoring System, the mainstay model.

They found that a combination of older age, low platelet counts, anemia, a higher percentage of cancerous cells, or blasts, in the bone marrow and poor-risk cytogenetics (aberrant chromosomes) divided the 856 patients into three clearly defined groups: When researchers applied the IPSS to the same patients, it failed to segregate patients with low or intermediate risk into the new test's risk categories.

Garcia-Manero says the scoring system is being applied in prospective clinical trials that are under way or planned at M. D. Anderson.

In the past three 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. Half the patients in the new study over the 30-year period died, and 90 percent of those were of myelodysplastic syndrome that had not transformed into AML, the researchers note.

"Identifying these low-risk, poor prognosis patients could allow us to be more aggressive, using medication at an earlier stage," Garcia-Manero notes. Few patients rated as low-risk receive donor bone marrow transplants, but a poor prognostic score would allow earlier consideration of that approach.

Garcia-Manero says the study needs to be replicated by other researchers and tested in prospective clinical trials, some of which are under way. The analysis of 856 patients was retrospective.
-end-
Funding sources for this research were 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 are: Jenny Shan, Stefan Faderl, M.D., Jorge Cortes, M.D., Farhad Ravandi, M.D., Gautam Borthakur, M.D., William Wierda, M.D., Ph.D., Sherry Pierce and Hagop Kantarjian, M.D., all of the Department of Leukemia; and Jun Liu and Xuelin Huang, Ph.D., both of M. D. Anderson's Department of Biostatistics.

University of Texas M. D. Anderson Cancer Center

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