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On Sept 3, 1998 I was diagnosed with Myelodysplastic Syndrome, Refractory Anemia with Ring Sideroblasts . It was the second time in the hospital in four weeks, with anemia. My hemoglobin count was 6.2, and they transfused me with four pints of blood. This time they did a bone marrow test, blood test, and cat scans. Since Sept. I have had a transfusion every four weeks. The hematologists started me on Procrit (erythropoietin)for twelve weeks and took me off after 12 weeks. He then started me on B6. I have now been without a transfusion since 1/99, so I am keeping my fingers crossed, along with everything else..:-)


What are the Myelodysplastic Syndromes ?


There are five forms of myelodysplastic syndrome:

Refractory anemia
Refractory anemia with ring sideroblasts
Refractory anemia with excess blasts
Refractory anemia with excess blasts in transformation
Chronic myelomonocytic leukemia


The myelodysplastic syndromes (MDS) are a group of diseases in which the production of blood cells is severely disrupted. The term myelodysplasia may be used to refer to the effects of myelodysplastic syndrome on the bone marrow. In contrast to leukemia in which one type of blood cell is produced in excessively large numbers the production of any, and sometimes of all, types of blood cells is affected in myelodysplastic syndrome.

The poor quality of the blood cells produced means that a significant proportion of them are destroyed before they leave the bone marrow. This means that the levels of red cells, white cells and platelets in the blood may be abnormally low. When the levels of all types of blood cells are low the condition is called pancytopaenia.

Myelodysplastic syndrome is mainly seen in people over the age of 50 years and in this age group it is more common in men. In younger patients the numbers of men and women are about equal.

Treatment of myelodysplastic syndrome is mainly supportive, that is, intended to relieve the symptoms rather than to try to cure the disease. The condition is treatable but is not considered curable in most cases. The majority of patients with myelodysplastic syndrome are too old to be eligible for a bone marrow transplant. In younger patients a donor bone marrow transplant may lead to long-term disease-free survival. In rare cases patients with the less aggressive subtypes of myelodysplastic syndrome have been reported to spontaneously recover.


Myelodysplastic Syndrome and Leukemia


Myelodysplastic syndrome is sometimes described as preleukemia, because up to a third of cases may eventually progress to a leukemic state, usually acute myeloid leukemia. Most doctors now prefer the term myelodysplastic syndrome because preleukemia is misleading.

Even some cases which do not transform to acute myeloid leukemia may resemble acute leukaemia with increased numbers of primitive blast cells in the bone marrow. Cases like this are sometimes called "smouldering leukemia".

Myelodysplastic syndrome arises, like leukemia, from a single abnormal stem cell from which all the defective blood cells making up the abnormal marrow population are derived. Certain characteristic abnormalities affecting the chromosomes, which carry the genetic information of the cells, are frequently seen in myelodysplastic syndrome. The same defects are frequently found in acute myeloid leukemia. In leukemia the bone marrow contains a mixture of diseased and normal blood producing cells. In myelodysplasia, in contrast, the blood producing cells are all abnormal and are all derived from the same damaged stem cell.

Myelodysplasia affects all the blood cells but one or other specific problem such as anemia, infections due to low white cell count or bleeding due to low platelet count may dominate the clinical picture.

It is important to emphasise that progression to leukaemia only occurs in a minority of cases. If any patient is worried about this aspect of the disease they should discuss it fully with their doctor.



Causes


Most cases of myelodysplastic syndrome have no obvious cause. This is called idiopathic or primary myelodysplastic syndrome.

Some cases, particularly younger adults under the age of 30, will be patients who have been treated with radiotherapy or drugs for other cancers. In these cases the myelodysplastic syndrome is probably a complication of treatment. This is called secondary myelodysplastic syndrome or sometimes referred to as treatment-related myelodysplastic syndrome.

In rare cases there appears to be a familial tendency to develop myelodysplastic syndrome. This only applies to a very small minority of cases. Exposure to high levels of benzene may increase the risk of myelodysplastic syndrome.

Types of Myelodysplastic Syndrome

There is a generally accepted classification system for myelodysplastic syndrome which is based on the appearance of the bone marrow and the results of specialised laboratory tests. This system is called the FAB system in recognition of the group of French, American and British haematologists who designed the system.

The FAB type is of great value in predicting the likely progress of the disease and the degree to which blood cell production is disrupted. The different forms of the disease vary in how aggressive they are clinically. The principles of treatment are the same for all forms of the disease.

There are five types of myelodysplastic syndrome in the FAB system. These are:
Refractory anemia
Refractory anemia with ring sideroblasts
Refractory anemia with excess blasts
Refractory anemia with excess blasts in transformation
Chronic myelomonocytic leukemia
Refractory Anemia (RA)

The marrow cells which produce red cells appear abnormal. The white cell and platelet producing cells may also appear abnormal but the proportion of primitive cells (blast cells) is similar to normal.

RA accounts for about 20 to 30% of cases. Transformation of RA to acute leukaemia is rare. The median survival ranges from two to five years. Some patients with RA survive well in excess of five years.



Refractory Anemia with Ring Sideroblasts (RAS)

The same changes are seen as in RA but there are additional abnormalities in the red cell population. As the red cell precursors become more defective they are unable to use iron to make the haemoglobin to carry oxygen around the circulation. Instead, the iron is deposited in characteristic rings in the red cell. These cells are called ring sideroblasts. This accounts for about 2 to 5% of patients and has an identical outlook to RA.



Refractory Anemia with Excess Blasts (RAEB)

In this form there are abnormal primitive white cells and platelet precursors called blasts. This indicates increasing abnormalities in blood cell production. This form accounts for about one-third of myelodysplastic syndrome and has a median survival of about six to nine months. About 40% of patients with RAEB will go on to develop acute leukemia.



Refractory Anemia with Excess Blasts in Transformation (RAEB-t)

The bone marrow in RAEB-t shows many features of acute leukemia. The distinction between this and leukemia is based on the percentage of marrow cells that are primitive blasts. About 25% of patients present with this form of myelodysplastic syndrome. The median survival is six months or less. The rate of transformation to overt leukaemia is between 60 and 75%.



Chronic Myelomonocytic Leukemia (CMML)

In CMML the red cell precursors usually appear abnormal. A mild reduction in the platelet count is often present. There is an increase in the number of monocytes in the blood and the marrow may or may not contain an increased proportion of blast cells. There may be anemia. CMML is considered a form of myelodysplastic syndrome because of the similar appearance of the bone marrow. Transformation of CMML to acute leukemia happens in a similar way to other forms of myelodysplastic syndrome. This type accounts for approximately 15%-20% of myelodysplastic syndromes. Median survival is of the order of 12-18 months. Approximately 30% of patients progress to acute leukemia.



Signs and Symptoms


Some patients with myelodysplastic syndrome will have no symptoms at the time of diagnosis. The most common symptoms are those due to the low red cell count (anemia), these include excessive breathlessness and tiredness.


The usual signs and symptoms are:

excessive tiredness on exertion
breathlessness
bleeding
easy bruising
infection
enlargement of spleen or liver

Tiredness and weakness are caused by the anemia. Bruising and/or bleeding problems result from a low platelet count. Infection may be a problem despite a sometimes apparently high white cell count because there are very few healthy white cells in the circulation.

Patients may show any combination of these symptoms. Some may be more obvious than others. Initial symptoms may appear to be nothing worse than a bout of flu.

Later in the disease more severe bleeding problems and severe infections may become a problem.

Anyone who develops any of the following signs or symptoms should see a doctor:
fever which persists more than a few days
weakness or persistent tiredness
swelling in the abdomen
bleeding problems e.g. heavy periods, blood in the stool, bleeding gums when cleaning teeth
unexplained or widespread bruising
bone pain


Diagnosis


Myelodysplastic syndrome is occasionally found by chance in the course of a routine blood test or a test for some other illness. Most patients will have been referred for tests with a clinical diagnosis of anemia.


Full Blood Count

This is a test which measures the different types of blood cell and the haemoglobin level.

A patient with myelodysplastic syndrome will have a low red cell and platelet count and be anemic. The white cell count may be lower than normal values.

The full blood count is done on a machine and the results may give an indication that the patient has myelodysplastic syndrome.

The general practitioner may take a blood sample and send it to the pathology laboratory or the patient may be sent to the laboratory to have blood taken. In either case, if the blood count suggests myelodysplastic syndrome the patient or the family doctor will be contacted by the hospital. A repeat count will be done (to confirm the result) and further tests will be arranged.


Blood Film Report

When the results of a full blood count are abnormal a blood film will be examined under the microscope.


Bone Marrow Biopsy

In all patients with myelodysplastic syndrome a bone marrow sample will be required. This involves obtaining a small amount of marrow from inside the bone with a needle, and a sample from the bone itself showing the structure of the bone marrow cavity. The first is known as a bone marrow aspirate, the second as a bone marrow trephine. The samples are usually obtained from the back of the hip bone, although the sternum (breast bone) may be used instead for bone marrow aspirates (but not for trephines). The procedure causes some discomfort but does not take very long. The procedure is usually carried out with sedation as well as local anaesthetic.

The blood film in myelodysplastic syndrome usually shows distinctive abnormalities of the red blood cells. It is still necessary to have a bone marrow biopsy to confirm the diagnosis and to allow sub-typing of the condition.

The type of myelo-dysplastic syndrome is very important in predicting the likely behaviour of the disease. A bone marrow biopsy will also provide cells for chromosome analysis.


Chromosome Analysis

This may be done on the cells from the blood, the bone marrow or both. In myelodysplastic syndrome there are typical changes in the chromosomes of the bone marrow cells when these are compared to normal cells from the same patient. The exact pattern of these changes may be important in predicting the likely response to treatment.

The initial diagnosis will probably be done at a local hospital but the patient may well be referred to a specialist centre for treatment.



Treatment


In the majority of patients with myelodysplastic syndrome treatment is aimed at controlling the symptoms and improving the quality of life for the patient. In the older patient there is no evidence that any treatment will improve the overall survival. Because the condition is so variable treatment tends to differ for each patient. The treatment of patients with secondary myelodysplastic syndrome is basically the same as for the primary disease but they tend to be less likely to respond to drug treatment.

No specific treatment has been developed for the myelodysplastic syndromes and for most patients treatment is aimed at relieving symptoms. This can usually be done by giving red cell or platelet transfusion when necessary.

Patients who have only mild anemia will require no treatment. The mainstay of treatment for symptomatic patients is the use of blood transfusions to control anemia. In a small percentage of patients it may be possible to improve the red cell count by giving injections of the hormone erythropoietin. Platelets can be given to patients for whom bleeding is a particularly marked problem. Platelets are not given routinely because they do not last very long in the circulation. Excessively frequent platelet administration could lead to the development of antibodies against the patientís own platelets or against donor platelets which may make future treatment less effective.

Patients with very low white counts may require antibiotics to prevent infections. In these patients any infection which does develop is likely to need hospital treatment.



Drug Treatment


During the early stages of disease drugs are not routinely used because the patient can feel relatively well with just the support of blood transfusions.

The use of cell-killing, cytotoxic, drugs has occasionally been beneficial but results are generally disappointing. When the disease does respond to treatment the effect is often brief.

High doses of chemotherapy, as used for acute myeloid leukemia, have been used with benefit for selected patients with the RAEB or RAEB-t sub-types of myelodysplastic syndrome.

Recently new drugs called G-CSF or GM-CSF have been introduced for treatment of blood and bone marrow diseases. G-CSF and GM-CSF are natural substances called growth factors produced in the body to control the production of white blood cells. They can be used in treatment to stimulate the production of normal granulocytes and monocytes.

In patients with myelodysplastic syndrome injections of growth factors usually increase the white blood count but the count returns to pre-treatment levels when the injections stop. The effect of growth factors on the number and severity of infections and on the disease progression is not yet known.

Therapies such as the use of vitamins A and D3 which aim to correct the failure in production of fully mature normal blood cells are also being evaluated. These drugs are known as differentiation agents.

With the exception of bone marrow transplantation for younger patients all studies so far have shown that the type of the disease is more important in predicting the length of survival than the treatment given.



Bone Marrow Transplantation


The majority of patients with myelodysplastic syndrome are over 60 years of age and therefore are not eligible for a bone marrow transplant. This is because the risks associated with transplants in older patients are greater than the potential benefits.

For young patients with myelodysplastic syndrome who have a donor available, bone marrow transplantation offers the potential for long-term, disease free survival. The outcome of bone marrow transplantation tends to be better in those younger patients who have fewer immature blast cells in the bone marrow, but long-term benefit has been noted in all FAB types.



So when you hear of a drive for bone marrow doners in your area, PLEASE go get tested.


It only hurts a little..:-)








This AA-MDS site owned by Jacqui Roth.
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Some Links for information on MDS



Myelodysplastic Syndrome Foundation

Ask NOAH About: Cancer

OncoLink

Diagnosis and Management of Anemia in Patients With the Myelodysplastic Syndrome

Leukaemia Research Fund

Leah's Homepage

Katy's Homepage

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