Myelodysplastic Syndrome

What It Is, How It’s Treated and How to Cope

Myelodysplastic syndrome (MDS) is an illness in which the body’s bone marrow doesn’t make blood cells properly. The bone marrow makes cells that are dysfunctional and these blood cells are destroyed before they leave the bone marrow or on entering the b loodstream. People who have myelodysplastic syndrome don’t have enough blood cells in their bodies to keep them healthy and a blood test will reveal a very low blood count.

MDS is viewed as a kind of cancer because the abnormal blood cells that are found in the bone marrow are all identical – the blood cells seem to ‘clone’ themselves just like certain cancer cells – with all the damaged cells starting from a single abnormal cell. MDS sometimes (30% of cases) develops into acute myeloid leukemia which grows very quickly in cells of the bone marrow.

It is possible that MDS is an early phase of leukemia, despite the fact that many people may never develop the disease. For this reason MDS used to be called pre-leukemia or smoldering leukemia.

In most forms of cancer the damaged cells live for a much longer time than normal, healthy cells and then gather together to overgrow the good cells in the body but in MDS the cells are not able to function normally and die faster than normal cells in the body. So why are they damaging? The cells tend to multiply faster than do normal cells and do gather together, but very slowly.

How Does Myelodysplastic Syndrome Occur in the Bone Marrow?

The soft inner portion of our bones (skull, shoulder blades, ribs, pelvis and backbones) is called bone marrow and it consists mainly of cells that form blood, fat cells and tissues that helps the blood-forming cells to grow.

Stem cells found in the bone marrow are the substances that make new blood cells. Some of these continue to function as stem cells with the rest going on to form either red blood cells, white blood cells or platelets.

The red blood cells in out bodies carry hemoglobin – a substance that channels oxygen from the lungs to our body tissues, platelets are responsible for helping the body seal wounds in blood vessels when we bruise or cut ourselves and are not strictly speaking a blood cell but rather sections of bone marrow cells called megakayocytes.

White blood cells or ‘leukocytes’ help to defend the body against infective processes and are divided into lymphocytes and granulocytes.

White blood cells, also known as leukocytes, are important in defending the body against infection. The 2 major types of white blood cells are lymphocytes and granulocytes which destroy bacteria. Often the first sign of MDS is low numbers of white blood cells leading to frequent infections.

Are there Different Kinds of Myelodysplastic Syndrome?

As determined by the World Health Organization, there are eight categories of MDS:

• Refractory anemia

• Refractory anemia with ringed sideroblasts

• Refractory cytopenia with multilineage dysplasia

• Refractory cytopenia with multilineage dysplasia and ringed sideroblasts

• Refractory anemia with excess blasts-1(RAEB-1)

• Refractory anemia with excess blasts-2(RAEB-2)

• Myelodysplastic syndrome, unclassified (MDS-U)

• MDS associated with isolated del(5q)

These categories are based on the prognosis for each disease related to the way the cells in the bone marrow look.

Refractory Anemia

This is where only anemia occurs. The cells that go on to form red blood cells look abnormal under a microscope (dysplasia). The number of early cells that is produced is normal but the red blood cells in the bone marrow may show iron deposits in a ring structure. Five to ten percent of patients with MDS have refractory anemia and it usually doesn’t cause acute myeloid leukemia.

Refractory anemia with ringed sideroblasts

This is like refractory anemia but there are more ring sideroblasts in their bone marrow. Ten to fifteen percent of people with MDS fall into this category and it usually doesn’t develop into leukemia.

Refractory cytopenia with multilineage dysplasia

This is where at least two of the three kinds of blood cells are low in number and. Two of the cell types in the bone marrow look abnormal when examined. About 25% of people with MDS have this type and in about 10% of patients it will go on to develop into leukemia.

Refractory cytopenia with multilineage dysplasia and ringed sideroblasts

Again, at least two of the three kinds of blood cells are low in number and two of the cell types in the bone marrow look abnormal under the microscope (dysplasia). Fifteen percent of patients show these signs and leukemia is common in about 10% of cases.

Refractory anemia with excess blasts (types 1 and 2)

One of the three blood cell types is low in number and look abnormal. This type makes up 40% of all patients with MDS and there is a 25% chance of the syndrome developing into acute myeloid leukemia with type 1 and 33% with type 2.

Myelodysplastic syndrome, unclassified (MDS-U)

One of the three blood cell types is low in number and either the white or megakaryocyte cell series looks abnormal when examined. It is not a common form of the disease and the chance of developing leukemia is very low.

MDS associated with isolated del(5q)

Anemia is the only feature of this disease and tests reveal that part of their chromosome number 5 is missing. It rarely develops into leukemia.

MDS can be classified according to bone marrow and circulating blood cell counts as well is determining if the MDS is ‘primary’ or ‘secondary’ In primary MDS the patient has no risk factor but secondary MDS can be linked to several different causes as discussed below and is hard to treat.

What are the Symptoms of Myelodysplastic Syndrome?

There are several symptoms which may indicate that a patient has MDS. These are caused by a shortage of blood cells:

• Excessive tiredness, shortness of breath, and pale skin can occur and may be caused by anemia (shortage of red blood cells).

• Severe infectious diseases with high fevers can be occur and can be caused by leukopenia (not having enough normal white blood cells) and by having too few mature granulocytes).

• Bruising and bleeding like frequent or severe nosebleeds and/or bleeding from the gums can be due to thrombocytopenia i.e. not having enough blood platelets that seal damaged blood vessels.

Your doctor will also look at cells from your blood and bone marrow to help him make a diagnosis.

Risk Factors for Myelodysplastic Syndrome

A risk factor is something that may increase your chance of getting a certain disease but it does not mean that you are certain to become ill with a specific condition. The risk factors that have been identified for MDS include:

Smoking

This is a lifestyle-related risk factor that is suspected for myelodysplastic syndrome. It can affect any cell in the body – even those with which it does not come into direct contact. The cancer-causing agents in cigarettes are absorbed into the bloodstream and can spread almost anywhere in the body.

Environmental exposures

Radiation and certain other chemicals are linked to MDS for example high-dose radiation exposure and long-term exposure to benzene or chemicals used to make petroleum and rubber can increase your risk of developing MDS.

Cancer treatment

Treatment with certain chemotherapy drugs is the most important risk factor for MDS. Drugs that can cause MDS are mechlorethamine, procarbazine, chlorambucil, etoposide, teniposide, and cyclophosphamide and doxorubicin.

If these drugs are given together with radiation therapy the risk is increased. Many of these cases occur after treatment for Hodgkin disease, non-Hodgkin lymphoma, or childhood acute lymphocytic leukemia. They can also occur after treatment for breast, lung, ovarian, testicular, gastrointestinal system, or other cancers.

Patients who have had stem cell transplants (bone marrow transplants) and are given very high doses of chemotherapy are now developing MDS as well.

Congenital diseases

Patients with Fanconi anemia have a greatly increased risk of developing leukemia or MDS as a child or young adult. People with Fanconi anemia have a shortage of one or more kinds blood cell and could also show malfunctions of limbs and internal organs. Other findings include light or dark spots on the skin, shorter height than expected for the child's age, and deafness.

Familial MDS

MDS is also found to occur frequently in adults in some families.

Age - This could be the greatest risk factor as MDS is a disease most commonly seen in elderly people.

Sex - MDS is slightly more common in men.

How is Myelodysplastic Syndrome Treated?

Chemotherapy

MDS is treated with chemotherapy drugs which are a kind of ant-cancer drug taken by mouth or injected into a vein or muscle. In MDS patients who are taking intensive chemotherapy a semi-permanent plastic tube may be placed into a large vein with the end of the tube lying under the skin of the chest area. Drugs are then injected into this tube or blood samples taken easily.

Once the drugs are in the bloodstream they can reach almost all parts of the body and because MDS is widespread in the body, chemotherapy is the ideal treatment option. The goal of treatment with chemotherapy drugs is to stop the abnormal stem cells and give the normal, healthy cells a chance to grow.

Since the drugs used in these treatments can also damage normal cells there are side effects to chemotherapy treatment. You may be given a single drug or various combinations of drugs. The drugs attack cells that are dividing quickly so tissues like those of the lining of the mouth and intestines and hair follicles are affected.

You may not get all or even any of these effects and how your body is impacted depends on which drugs you are given and for how long. Once the treatment is over, your cells will re-grow and the symptoms should subside.

You may experience one or more of the following side effects while undergoing treatment:

• Hair loss

• Mouth sores

• Appetite loss

• Nausea, and vomiting.

• Lowered infection resistance due to low numbers of white blood cells

• Easy bruising or bleeding due to low numbers of blood platelets

• Fatigue due to low red blood cell numbers.

If you are bothered by side effects such as these your doctor can give you other drugs together with your chemotherapy to minimize effects like nausea and vomiting or to increase your blood counts to a healthy level so you can avoid infections.

During chemotherapy organ damage may occur such as to the kidneys, liver, testes, ovaries, brain, heart, and lungs but your doctor will monitor you carefully to make sure that these effects are avoided and stop medication that causes damage.

Differentiation Agents

These are substances that allow bone marrow blasts to form into mature blood cells and a drug called azacitidine has been approved by the FDA for treating MDS. The goal of treatment is to alter DNA in the cells and render them normal. This is similar to drugs used in chemotherapy so it can lower blood counts and it used with care.

Arsenic trioxide causes immature cells to mature and has shown some success in treating some patients. It is taken intravenously and has few side effects.

Angiogenesis Inhibitors

Angiogenesis is the process of developing new blood vessels and can aggravate the development of cancer cells. If a patient is given a drug to stop the development of these vessels the disease can be slowed down. Thalidomide, has had some mild success in treating MDS and it can help avoid needing blood transfusions because they were able to make their own red blood cells or their granulocyte counts and platelet counts.

There are side effects like drowsiness, fatigue, and constipation, however and new drugs are currently being developed that are similar to thalidomide but without the side effects.

How to Cope with MDS

If your white blood cells are very low you should take steps to avoid infection such as:

• Avoiding exposure to bacteria, fungi, or viruses.

• Wearing a surgical mask around crowds and construction areas.

• Washing hands and avoiding fresh, uncooked fruit and other foods that might carry germs.

• Taking powerful antibiotics before signs of infection or at the earliest sign that one is developing.

Always eat a balanced diet, take moderate exercise and take steps to deal with any psychological issues that may be troubling you.

The type of treatment you will be given depends on the type of disease you have, your age and your general health. Talk to your doctor about your illness, the aims of treatment and the side effects of the drugs you will be prescribed. You may feel anxious about your disease and opening the channels of communication between your caregivers and family members will help you stay strong enough to fight your illness.