Myelodysplastic syndromes (MDS) are a group of diseases that originate in an early blood-forming cell in the marrow. In patients with this disorder, the marrow produces too few red blood cells, white blood cells and often platelets. In the myelodysplastic syndromes, the maturing blood cells often die in the marrow before they reach full maturity and enter the blood, accounting for the low blood cell concentrations. There may also be an accumulation of very immature marrow cells, called leukemic blast cells.
The severity of the marrow cell disturbance is varied and can range from mild to very severe.
Thus, the disease may be indolent or chronic and be manifest primarily as mild anemia; it may have severe decreases in red and white blood cells and platelets and be more troublesome; or it may have severe decreases in blood cells and have leukemic blast cells in the marrow and be even more threatening to the health of the patient. In addition, the disease can progress such that the leukemic blast cells take over the marrow and the disease evolves into acute myelogenous leukemia. The marked decrease in blood cell formation makes it difficult for patients to prevent or fight infection and it predisposes them to exaggerated bleeding.
The annual incidence worldwide may be in the range of 4,000 to 6,000 cases per year. The age of onset closely follows that of acute myelogenous leukemia, increasing dramatically after age 50. The disorder affects both genders but, like other leukemias, is more common in men than women.
Although myelodysplastic syndrome covers a spectrum of neoplastic myeloid diseases, most cases can be placed into several subgroups based on the blood cell counts and the appearance of blood cells under the microscope. The two principal subgroups are:
Chronic and Nonprogressive Anemia
Blood cell count deficiencies without evidence of leukemic blast cells make up about one third of the myelodysplastic disorders. The disorder may cause principally a deficiency 1) of red cells, 2) of red cells and white cells or 3) of red cells, white cells and platelets. These situations are often referred to as refractory anemia (even though white cell and platelet counts may be low as well as red cell counts). These situations may be nonprogressive for years or decades. If the blood-cell count deficiencies are mild, the circumstance may have little effect on the patient’s ability to conduct his or her usual activities. About 10 to 15 percent of patients in this subgroup may later develop acute myelogenous leukemia.
Progressive and Symptomatic Blood Cell Deficiencies
The second principal subgroup of myelodysplastic disease shows evidence of leukemic blast cells in the marrow. This finding is associated often with low red cell, white cell and platelet counts, and other changes of blood cell shape and structure under the microscope that is characteristic of these leukemic syndromes. This category of disease has been variously designated as low blast count myelogenous leukemia, refractory anemia with excess blasts, smoldering leukemia and other designations. Like the other category of myelodysplastic syndrome, it may have a wide range of severity and a difference in the rate of worsening. If the leukemic blast count was high the designation “refractory anemia with excess blasts in transition” (to acute myelogenous leukemia) was used but the designation is not useful and it has been recommended that it be dropped. (Table 1). Such patients are considered to have acute myelogenous leukemia. In fact, these disorders are each gradations of severity of myelogenous leukemia. The proportion of leukemic blasts cells in the marrow and the degree of the abnormalities in blood cell counts correlates with the rate of progression of the disease.
Causes and Risk Factors
In most cases the disease has no external cause. The use of certain drugs that are designed to damage DNA and are used to treat lymphoma, myeloma or other cancers, such as breast or ovarian cancer, increase the risk of developing acute myelogenous leukemia or a myelodysplastic disorder. The same sequence of events can follow the use of therapeutic radiation for lymphoma. Benzene exposure above threshold levels for protracted periods of time, usually in an industrial setting, may increase the incidence of acute myelogenous leukemia and may precede the onset of myelodysplasia. The increasingly stringent regulation of benzene use in the workplace has diminished this sequence of events.