Myelodysplastic sydrome (MDS) is a disorder in which the bone marrow stops being able to produce enough blood cells. It is caused by acquired (that is, not inherited) genetic damage to the marrow stem cells and mainly affects those over age sixty. The reason for the stem cell damage is usually unknown, although some cases are caused by exposure to benzene, radiation, or certain types of chemotherapy.
Analysis of the name “myelodysplasia” is the first step toward understanding this confusing disorder: myelo is Greek for marrow, dys means abnormal, and -plasia means formation or development. Thus, myelodysplasia means abnormal bone marrow development. The result is insufficient blood formation for the needs of the body.
MDS is usually diagnosed when weakness, infection, or bleeding causes a person to seek medical help; some cases are found on routine blood testing before symptoms arise. Analysis of the CBC will show reductions in one, two, or three of the blood counts (red, white, platelets).
The patient will then be referred to a hematologist, who will rule out other causes of low blood counts (such as deficiencies of vitamin B12, folic acid, and iron) and perform a bone marrow biopsy.
A curious finding in MDS is that, although the disorder is characterized by lower than normal blood counts, a patient’s bone marrow will often exhibit an excess of blood-producing cells compared to normal.
The appearance of the MDS marrow cells, however, is bizarre; they are misshapen, abnormally enlarged, and altered in a way that enables them to be labeled “dysplastic.” The problem is that the exuberant growth is exceeded by accelerated cell death: instead of releasing healthy blood cells into the circulation, MDS cells mostly die in the bone marrow.
Although MDS is not a cancer, the dysplastic and damaged marrow stem cells are primed to sustain further damage and be converted into leukemia. The likelihood of conversion to leukemia can be predicted with some accuracy and is highly correlated with overall survival (the greater the chance of leukemia, the lower the survival). The method of prediction is called the International Prognostic Scoring System (IPSS).
The IPSS uses three criteria to determine if a patient has a low, intermediate, or high risk of developing leukemia. They are:
1. The percentage of bone marrow cells that are leukemia blasts (ranging from less than 5 percent to 20 percent).
2. The chromosome pattern of the bone marrow cells.
3. The number of blood counts (one, two, or three) that are low, considering the red cells, white cells, and platelets.
An MDS patient’s hematologist will calculate the IPSS score and risk category, which will dictate the possible treatments. Those with low or low to intermediate scores may need only a low-intensity approach to maintain their blood counts, such as blood transfusions or injections of blood cell growth factors. Those with intermediate to high IPSS scores may require chemotherapy followed by a stem cell transplant from another person in an effort to eradicate the diseased marrow. Patients with any score may benefit from the drug azacytidine (Vidaza), which is a form of low-intensity chemotherapy. When Vidaza works well, it can diminish the need for blood transfusions, delay the onset of leukemia, and extend life.
The related drug decitabine (Dacogen) was recently approved by the FDA for use in MDS patients with high or intermediate IPSS categories. Some patients may benefit from infusions of antithymocyte globulin (ATG), a horse or rabbit serum that suppresses the immune system (which may be attacking the bone marrow).
A special category of MDS is that characterized by a 5q minus chromosome abnormality (also called deletion 5q). Patients with such an abnormality in their bone marrow may respond well to the drug lenalidomide (Revlimid), which can induce dramatic improvements in red blood counts and liberate them from blood transfusions.
