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Blood - Acute Leukemia

genetic clinical cells adults patients normal

The term leukemia comes from the Greek, meaning "white blood," and refers to a set of diseases in which neoplastic white blood cells (blasts) accumulate in the blood and bone marrow. These cells fail to differentiate into mature, functional cells of the eight normal lineages, and furthermore suppress the growth of normal blood cells. The symptoms of acute leukemia are a consequence of a lack of normal red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia), deficiencies that result, respectively, in fatigue, susceptibility to infection, and bruising or bleeding. This disease progresses rapidly, and without treatment is invariably fatal, usually within weeks or months. The treatment of acute leukemia is based upon the use of chemotherapy and radiation therapy, sometimes with the addition of bone marrow transplantation. The goal of these treatments is to destroy all of the leukemic blasts, and to allow the residual normal HSCs to repopulate the bone marrow and restore normal blood production. The first aim of treatment is to eradicate all detectable leukemic blasts in a patient—if this is achieved, the disease is said to be in remission. Remission is not, however, tantamount to cure; almost invariably a small number of leukemic cells survive the therapy and eventually the leukemia returns or relapses. Acute leukemia may develop from preexisting myelodysplasia, or it may arise de novo. Like myelodysplasia, acute leukemia is more common in older adults than in younger adults; approximately 60 percent of cases are diagnosed in patients older than sixty years. Numerous clinical studies have shown, however, that older adults with acute leukemia are significantly less likely to achieve remission or cure than are younger patients. Currently, even with the best available therapy, few people older than sixty years diagnosed with acute leukemia survive longer than three years. There are likely two reasons for this poorer prognosis. First, the therapies for acute leukemia are themselves toxic and harsh. Older patients are more likely to have other significant health problems, and are therefore more susceptible to the adverse effects of therapy and are less likely to receive as high a dose. Second, the biology of acute leukemia appears to be different in older adults, perhaps because of accumulation of additional genetic mutations in HSCs over time. In older adults, acute leukemia is more likely to follow a period of myelodysplasia (see above), or to occur after previous exposure to chemotherapy for another malignancy. Leukemia in older patients is also more likely to exhibit certain characteristic chromosomal abnormalities in the leukemic clone. These features are associated with a poorer response to therapy, whether in younger or older patients.

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