The Myelodysplastic Syndrome

This is a common cause of anemia in the elderly. As people age, the bone marrow begins to mal-function and looses its ability to produce healthy white cells, healthy red cells or platelets. The Bone Marrow All the blood cells are produced by the bone marrow. The bone marrow is located in the center of all the bones of the body. Commonly it’s the marrow in the vertebrae, the pelvis and the upper ends of the long bones that produce most of the blood. But in times of need, the other bones will kick in and allow their dormant marrow to be turned on. Blood is composed of liquid and solid particles. The liquid is mostly water containing very precious proteins, chemicals and hormones. The solid particles are 1. The Red Cells 2. The White Cells 3. The Platelets. The red cells are red because they contain hemoglobin, which carries the oxygen from the lungs to the tissues of the body; the same red cells pick up carbon dioxide from the tissues, the break down product of metabolism and take it back to the lungs where it is excreted to the air. There are between 4 and 6 millions red cells per cc of blood The white cells are called white because of the way they stain under the microscope. There are two types of white cells; the neutrophil and the lymphocyte. The neutrophil circulates in the blood ready to defend the body against bacterial invasion; the lymphocyte is an immune cell and is part of the immune system. (See Page on The Immune System and Cancer for a better understanding of lymphoma) There are about 10,000 white cells per cc of blood. Platelets are the smallest of the blood cells. They are tiny globular masses that patch up small holes in blood vessels. There are 250,000 platelets per cc of blood. The Stem Cell All the different cell populations of the body usually come from one progenitor cell, called a stem cell. The bone marrow has a small population of these pluripotential cells, which give rise to all the other cells in the blood. All the white cells, the red cells and the platelet, evolve from this small population of cells. The Stem Cell of the marrow is a pluripotential cell that has the growth potential and capacity to produce ANY OTHER CELL in the body, including heart muscle, liver and kidney. In the bone marrow, the stem cells produce a first generation of immature red cells, called normoblasts, immature white cells, called myeloblasts and large platelet-producing cells called megakaryoblast. The normoblasts mature and differentiate, by going through a few more cell divisions, before evolving into mature red cells; the myeloblasts mature into normal neutrophils in a similar fashion. The megakaryoblasts grow large and produce thousands of platelets, from its nucleus, and then its membranes release its cell contents into the plasma. The lymphocytes evolve from lymphoblasts that are present in both the bone marrow and lymph nodes. How the Dysplasia Occurs Dysplasia means abnormal growth and differentiation. Genetic mutations occur in the genome and the normal cell-signaling system breaks down. The Stem Cells do not smoothly move from one generation to the next and get stuck either as normoblasts or myeloblasts. The Stem Cells may continue to mature through the early generations but the rate of maturation is slowed and cells pile up at different stages producing a crowded atypical population of cells. The Stem Cells will sometimes mature but the red cells or the white cells are abnormal and do not function properly. The red cells have ringer sideroblasts (red cells overloaded with iron, which gives them a characteristic recognizable appearance) Because of its Dysplastic nature, the disease is subclassifed into four different types: 1. Refractory anemia (RA) (where red cells only are decreased) or refractory cytopenia (RC) (Where red cells, white cells and platelets are decreased) 2. Refractory anemia with ringed sideroblasts (RARS) 3. Refractory anemia with excess blasts (RAEB) 4. Refractory anemia with excess blasts in transformation. (RAEBT) Type 1 can evolve into type 2, 3 or 4; type 2 can advance into type 3, or 4. The differential and maturating growth of the cells is affected by the genetic mutations that cause the disease. The phenomenon occurs sporadically and may be a disease of aging. In sporadic Myelodysplastic Syndrome, the long arm of chromosome 5 is frequently missing. The absents of this piece of the chromosome allows other chromosomal changes to occur and leads to more problems. The Myelodysplastic Syndrome that follows due to the previous treatment of a malignancy are easy to differentiate from the sporadic type. If the patient has been treated previously with either chemotherapy or radiation therapy, then these agent may be the cause. There are usually two types of treatments that can cause the specific chromosomal changes. 1. Radiation Therapy or alkylating agents (Nitrogen Mustard, Cytoxan, Alkeran, Busulphan). These cells have a complete deletion of chromosome 13, with the loss of part or all or chromosome 5 and 7. 2. Topo-isomerase Inhibitors. (Etoposide) These cells have multiple DNA strand breaks so translocations of chromosomes occur. Chromosome 11 will adhere with chromosome 4, 9, or 19. The effects of radiation therapy take a long time to affect the marrow i.e. up to twenty years. Topo-isomerase inhibitors take about two years to affect the marrow. Prognosis And Treatment The prognosis depends on what stage the disease is at, when it is diagnosed. It is frequently a disease of the elderly, who often have other diseases at the time of diagnosis. If it is at the anemic stage; expectant observation is all that is needed. As long as the disease remains stable, no treatment is needed. If the anemia gets slowly worse, then intermittent blood transfusions may suffice for a period of time. If the frequently of blood transfusion is increasing, then a trail of Epogen should be tried. If Epogen does not work as a single drug, then Neupogen can be added and this may have an additive effect on stimulating the marrow. Patients, who present with low blood counts, after having had radiation therapy or chemotherapy or both, previously, may have to be treated more aggressively. If the blast cells are increasing in the marrow, then patients may have to be treated with chemotherapy or high dose chemotherapy with stem cell rescue. The treatment for this disease is complicated and the judgments used when to treat, with what, is beyond the brief discussion. If you wish to know more about this disease or the drugs used to treat it, then call my office for an appointment and I will be happy to give you a second opinion on the management of your particular disease.