Low-Dose Decitabine Produces Improved Blood Counts in Some Elderly Persons
Researchers from Europe report that there may be a new treatment option for elderly persons and others who cannot tolerate the side effects of the potentially curative regimen of high-dose chemotherapy and stem cell transplantation. A recent study shows that a drug, called decitabine, produces improved blood counts in some older persons.
A myelodysplastic syndrome is a disease in which the cells in a person’s bone marrow are not functioning normally. The bone marrow (and circulating blood) contains early blood-forming cells, called stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). In the case of myelodysplastic syndromes, not enough normal blood cells are being produced. This condition is sometimes referred to as a pre-leukemia or “smoldering” leukemia, because it often develops into leukemia, a type of cancer. Some persons with myelodysplastic syndrome also have additional abnormalities, including genetic abnormalities of the blood cells, a high number of immature blood cells (called blasts) in the bone marrow, or decreasing numbers of red blood cells, white blood cells, or platelets. These persons are at a higher risk for a more rapid progression to leukemia than are those who have more favorable cell features.
Treatment of myelodysplastic syndromes often consists of the infusion of red blood cells or platelets to compensate for the inadequate production of these cells in the bone marrow. This therapy may ease the signs and symptoms of disease, such as anemia or fatigue, and may prolong survival time. The use of chemotherapy to kill the pre-cancer cells and the use of biologic therapy agents (immunotherapy) to help the immune system are being studied in clinical trials. One curative option may be the use of doses of chemotherapy that are higher ( high-dose chemotherapy) than the standard doses, with radiation therapy directed at the entire body. This high-dose chemotherapy can kill more pre-leukemia and leukemia cells than standard doses of chemotherapy; however, it can also damage healthy cells, especially the young stem cells in the bone marrow. For this reason, an SCT may be used in combination with high-dose chemotherapy and radiation therapy to “rescue” the bone marrow and enhance the production of new blood cells. Unfortunately, elderly persons often cannot tolerate the potential complications of the transplant procedure or the side effects of some chemotherapy drugs. Researchers in Europe studied the use of decitabine, a drug that is relatively non-toxic at low doses, to treat elderly persons with myelodysplastic syndrome.
Sixty-six persons, averaging 68 years of age, received low doses of decitabine (for 3 days every 6 weeks) for the treatment of myelodysplastic syndrome. Half of these patients had a response to treatment, showing improved blood counts. Of the 52 persons who had at least 1 course of decitabine, 66% experienced an increase in platelet counts. The highest response rates were observed in persons who had the high-risk type of myelodysplastic syndrome with severe cell genetic abnormalities. The average duration of response was 31 weeks. Seven percent of patients died from treatment-related effects, usually low blood counts.
These findings show that decitabine may be an effective agent, resulting in responses and improved blood counts in many elderly individuals with high-risk myelodysplastic syndrome. This drug will likely be particularly useful when combined with biologic therapies or other agents, to improve the treatment outcomes of persons with myelodysplastic syndrome who cannot tolerate a stem cell transplant. Older persons who have a myelodysplastic syndrome may wish to talk with their doctor about the risks and benefits of the low-dose decitabine regimen, or of participating in a clinical trial in which other new treatments are being studied. Sources of information on ongoing clinical trials that can be discussed with a doctor include a comprehensive, easy-to-use service provided by the National Cancer Institute ( cancer.gov) and the Clinical Trials section and service offered by Cancer Consultants.com ( www.411cancer.com). ( Journal of Clinical Oncology, Vol 18, No 5, pp 956-968, 2000)
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