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Study recommends treatment change for pre-leukemia disease


A new study finds that longer courses of a mild form of chemotherapy may help patients with a bone marrow disease only recently considered a form of cancer. Writing in the April 15, 2006 issue of CANCER, a peer-reviewed journal of the American Cancer Society, researchers say the study found that 45 percent of patients with Myelodysplastic Syndrome (MDS) who relapse did respond to a second course of treatment, but that the quality and duration of the second response was inferior to the initial treatment, leading researchers to believe that longer initial treatments may be more beneficial to patient outcome.

MDS is a bone marrow disease that causes an increasing number of dysfunctional blood cells called blasts to develop from stem cells and proliferate in the blood stream at the expense of normal cells. As a result, fewer normal red blood cells will circulate to carry oxygen to cells resulting in anemia; fewer white blood cells will be available to fight infections; and fewer platelets to control bleeding. Although MDS has not been considered cancer in the past, most hematologists (specialists in diseases of the blood) now think it is a form of bone marrow cancer (i.e. leukemia).

MDS generally afflicts adults over 50 years old, and therapy is supportive rather than curative. However, a subset of MDS patients will develop blood cell cancer, or leukemia. These high-risk patients have been shown to benefit from a new DNA hypomethylating agent, decitabine, undergoing clinical trials. The results of these trials are revealed in a related article by Kantarjian et al. also published in the April 15, 2006 issue of CANCER.

Little is known about the optimal duration of treatment with decitabine and the effect of retreatment for relapse. Led by Michael Lübbert, M.D., Ph.D. of the University of Freiburg Medical Center in Freiburg, Germany, researchers assessed the efficacy of decitabine retreatment on relapsing high-risk MDS patients who received initial treatment with decitabine.

The researchers found that retreatment with a median of three courses of decitabine resulted in 10 patients out of 22 (45 percent) achieving any response. Three of the patients achieved a partial or complete response in all three cell lines, while the other seven patients experienced hematologic improvements of an at least 50 percent drop in transfusion requirements and higher counts in one or two blood cell lines. The median overall survival of all patients from the start of the first decitabine course was 28 months. Decitabine-retreated patients had a median survival of 13 months from relapse

Decitabine retreatment in the 12 patients (55 percent) not achieving a second response either suppressed the abnormal cells without bone marrow repopulation with normal cells, resulting in cytopenia (blood cell deficiency), or had no effect on normal or abnormal cell lines. Of these 12 retreatment failures, four patients developed acute leukemia and three patients died of complications due to pathological deficiencies in cell lines.

The authors conclude, "results of the present analysis point to the importance of extending therapy with low-dose decitabine beyond the point of first response, and strongly support institution of a maintenance treatment." This type of continued outpatient maintenance treatment is presently studied by the authors in a multicenter clinical trial in older patients with acute myeloid leukemia.

David Greenberg | EurekAlert!
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