The myelodysplastic syndromes (MDS) are a group of diseases in which the production of blood cells by the bone marrow is disrupted. In contrast to leukaemia, in which one specific type of blood cell (the white cell) is produced in excessively large numbers, the production of any, and sometimes of all, types of blood cells is affected.

The myelodysplastic syndromes were formerly referred to by many names including preleukaemia. The term preleukaemia is no longer used because it is very misleading. Although a minority of patients with MDS develop acute leukaemia, most do not. When leukaemic transformation does occur, it is to acute myeloid leukaemia (AML). This form of leukaemia is typically more difficult to treat than primary AML (cases arising in patients with no previous bone marrow disease).

The bone marrow in myelodysplastic syndrome is typically more active than normal and yet the numbers of blood cells in the circulation are reduced. This is because most of the cells being produced in the bone marrow are defective and are destroyed before they leave the bone marrow to enter the blood stream. The hallmark of the myelodysplastic syndromes is the combination of a hyperactive marrow with low blood cell counts. A reduction in numbers of all types of blood cell is called pancytopaenia. The other common feature of the myelodysplastic syndromes is abnormality in the appearance of the bone marrow and blood cells. These abnormalities (e.g. white cells lacking normal granules) are characteristic of the condition.

The myelodysplastic syndromes are difficult to treat because of the unusual combination of hyperactive marrow but inadequate blood cell production. The only treatment considered potentially curative is a donor stem cell transplant in younger and fitter patients. Unfortunately most patients are too old for this to be an option.

Classification

There are two main ways of classifying myelodysplastic syndrome. The FAB (French American British) system divides MDS into five subgroups. The World Health Organization (WHO) developed a different classification system with two main subgroups. These are:

  • Chronic and nonprogressive anemia - blood cell count deficiencies without evidence of leukemic blast cells
  • Progressive and symptomatic blood cell deficiencies - there are leukemic blast cells in the bone marrow

If the leukemic blast cells make up more than 20% of the bone marrow, the individual is considered to have acute myelogenous leukemia (blood cancer).

Can Myelodysplastic Syndromes Be Prevented?

Some studies have shown a statistical link between smoking and the risk of developing leukemia or myelodysplastic syndromes (MDS). Of course, nonsmokers are also less likely than smokers to develop many other specific cancers, as well as heart disease, stroke, and other diseases.

Treating other cancers with chemotherapy and radiation may cause secondary (post-treatment) MDS. Doctors are now studying ways to minimize the risk of secondary MDS developing in patients receiving these treatments. For example, in highly curable conditions such as Hodgkin disease, doctors may try to avoid using drugs that can lead to MDS. However, the obvious benefits of treating life-threatening cancers with chemotherapy and radiation therapy must be balanced against the small chance of developing MDS several years later.

Avoiding known cancer-causing industrial chemicals, such as benzene, might lower your risk of developing MDS. However, most people with MDS do not have any known exposure to occupational and environmental radiation and chemicals.

Can Myelodysplastic Syndromes Be Found Early?

Currently, no special tests are recommended for early detection of myelodysplastic syndromes (MDS) in the general population.

Follow-up physical exams and, in some cases, blood tests may help find some cases of MDS in cancer survivors previously treated with certain chemotherapy drugs.

Signs and Symptoms

Myelodysplastic syndromes (MDS) can cause many different signs and symptoms. Patients can have symptoms such as weight loss, fever, and loss of appetite. Of course, these do not occur only with MDS and are more often caused by something other than cancer.

Shortages of one or more types of blood cells can cause most signs and symptoms of MDS:

  • Excessive tiredness, shortness of breath, and pale skin can be caused by anemia (shortage of red blood cells).
  • Serious infections with high fevers can be caused by leukopenia (not having enough normal white blood cells) and, in particular, by having neutropenia or granulocytopenia (too few mature granulocytes).
  • Excessive bruising and bleeding (for example, frequent or severe nosebleeds and/or bleeding from the gums) can be due to thrombocytopenia (not having enough of the blood platelets needed for plugging holes in damaged blood vessels).

Patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) can have the same symptoms, except that they can have fullness in their abdomen, particularly the left side, caused by an enlarged spleen, which can be felt by the doctor. They may also notice enlarged lymph nodes.

Treatment

Treatment depends on the type of myelodysplastic syndrome present, including if blast cells are present and what type of abnormal chromosome exists. Many treatment options are available. It is also important to consider what other medical problems an individual might have, such as diabetes or high blood pressure, along with the myelodysplastic syndrome when considering treatment.

Because no definitive cure or treatment for myelodysplastic syndromes exists, most people receive supportive care, which is intended to help manage symptoms such as fatigue and to prevent bleeding and infections. Supportive care may include the following:

  • Transfusion therapy. People with anemia induced by myelodysplastic syndromes are likely to receive transfusions of red blood cells, which help relieve anemia and fatigue.

Much of the news about transfusion therapy is positive: Doctors usually have no trouble findi ng a matching blood type, transfused blood cells generally remain in the body a month or more, and there’s no limit to the number of transfusions you can receive. Although some people have concerns about the safety of transfused blood, the blood supply is closely monitored and accidental disease transmissions are rare.

Some problems exist, however. Over time, you may develop antibodies to transfused blood cells, making them less effective at relieving symptoms. And donor red blood cells contain iron that can build up in the body, causing liver and heart damage, especially in people who have had multiple transfusions over a period of years. To reduce the risk of iron overload, doctors use vitamin C along with an intravenous chelating agent that binds with iron, reducing its toxic effect.

Platelets also can be transfused, although the process is more complicated because the donor blood must be circulated through a machine to separate out the platelets. What’s more, you can develop antibodies to donor platelets fairly quickly. White cells, because they are so short-lived, aren’t usually transfused separately.

  • Drug therapy. Hematopoietic growth factors stimulate the production of blood cells. They occur naturally in the bone marrow but are also produced artificially. Some growth factors, such as erythropoietin or darbepoetin, can reduce the need for blood transfusions by increasing red blood cells. Others may help prevent infections by increasing white blood cells in people with certain myelodysplastic syndromes. Researchers are also studying growth factors that may encourage the bone marrow to produce platelets. Side effects of growth factors are usually minor and include temporary bone pain and fever.

The Food and Drug Administration has approved several drugs specifically for the treatment of myelodysplastic syndromes. Azacitidine (Vidaza) and decitabine (Dacogen), also called differentiation agents, work by stimulating blasts to develop into mature blood cells. These drugs may improve quality of life and help delay progression to acute myelogenous leukemia. But they aren’t effective in all people, and some can cause further blood cell problems.

Lenalidomide (Revlimid), a drug chemically related to thalidomide, may eliminate the need for blood transfusions in people with myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality. It also appears to have few side effects.

Other therapies

Although supportive care is the treatment of choice for most people with both primary and secondary myelodysplastic syndromes, other treatments sometimes may be an option:

  • Chemotherapy. This is sometimes used to destroy blasts in people with severe disease. But chemotherapy is seldom effective, and the risks usually far outweigh the benefits, especially in older adults.
  • Stem cell transplant. Replacing abnormal stem cells with healthy, donated cells (allogeneic transplant) has the most potential for prolonging life. Unfortunately, few people are candidates for this procedure because of the high risks involved in transplanting in older adults - those most likely to have myelodysplastic syndromes. Even among young, relatively healthy people, the number of transplant-related deaths is high.

A new approach called nonmyeloablative transplantation may make stem cell transplants less dangerous for older adults and improve outcomes overall. Instead of using chemotherapy to completely destroy the host’s stem cells before transplantation, this procedure suppresses the immune system just enough to prevent rejection of the donated cells

Sources: LRF, Rare Diseases

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