What is Myelodysplastic Syndrome (MDS)?
Myelodysplastic Syndrome or MDS is not a single disease but a group of disorders affecting the
bone marrow, with the abnormality being most prominently reflected as a lowering of blood counts.
In fact, one way to think of the complexity of MDS is to think of it as being to the bone marrow
what pneumonia is to the lungs; the response of an organ to a variety of causes like aging, toxic
exposure, infections, and auto-immunity. Amongst infections of the lungs alone, pneumonia could
be the result of a variety of possible pathogens including bacterial, viral, tuberculous, or fungal
agents. Similarly, MDS is the response of the bone marrow to a variety of unknown insults and cannot
be treated as a single disease. There are two things that all patients with MDS share; first there
is a lowering of one or more blood counts and second, the bone marrow cells look abnormal or "dysplastic".
Cells that are circulating in our blood are born in the bone marrow from a small number of primitive
"stem cells". MDS is a disease of A SINGLE bone marrow stem cell which then starts producing ineffective
and abnormal blood cells. There are two main forms of blood cells; Lymphoid and Myeloid. As the name implies,
MDS is a disease of the myeloid cells; dysplasia means that the cells look abnormal. Our blood contains three
types of myeloid cells; red blood cells or RBCs which carry oxygen in the form of hemoglobin to all parts of
the body, white blood cells or WBCs which are mainly responsible for fighting infections, and platelets which
stop bleeding. Lowering of RBCs leads to a decrease in hemoglobin or anemia. Decrease in WBCs, especially the
neutrophils (referred to as an absolute neutrophil count or ANC) increase the risk of infections. A decline in
platelets, especially a count under 30,000/ul, leads to a susceptibility towards bleeding. MDS patients present
with a lowering of one or more types of these blood cells, the most common cell type affected being red cells.
This makes anemia a universal hallmark of the disease. It is called Refractory Anemia because the anemia of MDS
patients does not respond to commonly employed therapies for anemia such as iron and vitamins.
The disease usually strikes older individuals, half the patients being older than 70 years of age. There are two
types of MDS, one for which no cause is known called primary or de novo MDS, and the other which follows known
and documented exposure to toxins/chemical agents such as benzene, chemotherapy, radiation therapy etc called
secondary MDS. The vast majority of patients constituting ~90% of the MDS cases belong to the Primary MDS category
while in <10% cases, the disease is a result of damage to the bone marrow produced by chemicals such as treatment
for a prior malignancy.
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Risk Factors
A risk factor is anything that may increase your chance of developing a disease. Different diseases, including cancer,
have different risk factors. Although these factors may put you at greater risk, they do not necessarily cause the
disease. Risk factors for MDS include:
- Smoking
- Age
- Environmental exposures
- Certain chemotherapy treatments for other cancers
- Stem cell transplants
- Congenital diseases
- A family history of MDS
- Sex (MDS is slightly more common in men)
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Symptoms
Lowering of the blood cells is known as cytopenias and therefore MDS patients may suffer from:
- mono-cytopenia (lowering of only one type of blood cells)
- i-cytopenia (two blood cell types) or
- pan-cytopenia (all three blood cell types).
Patients with MDS show symptoms related to the severity of the cytopenias as well as the number of cell types
affected. Patients with MDS present with one or more of the following blood abnormalities:
- Anemia or Low Red Blood Cell Count: Red cells produced in the bone marrow carry oxygen in the form of hemoglobin
via blood to all the tissues in our bodies.
If a patient has only lowering of the red blood cells, then symptoms will be related to anemia, including
increased tiredness, weakness, inability to exercise and participate in prolonged physical activities or exertion.
This is the most common type of cytopenia in MDS, being present in almost 90% patients.
- Leukopenia or Low White Blood Cell Count: Repeated or persistent infections may indicate involvement of white
blood cells. There are two main types of white cells in the blood, neutrophils which are responsible for fighting
bacterial infections, and lymphocytes which fight viral infections. The absolute neutrophil count or ANC can be
low in MDS patients.
- Thrombocytopenia or Low Platelet Count: These cells are involved in the prevention of bleeding and may be low
in MDS patients. Frequent bleeding episodes would suggest a lowering of platelets.
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Screening and Diagnosis
It must be noted that our body has an enormous reserve and ability to cope with abnormal situations so that
the disease may fail to produce any symptoms until greater than 90% of the function has been compromised.
This is why a diagnosis of MDS is often brought to light by a routine annual physical examination, which is
accompanied by a complete blood count or CBC.
- Anemia or Low Red Blood Cell Count: Red cells produced in the bone marrow carry oxygen in the form of
hemoglobin via blood to all the tissues in our bodies. The normal range of hemoglobin in the blood is
between 12.5 to 15.5 Gm/dL. In MDS patients, this level falls to below the normal range, the profundity of
anemia being a direct reflection of the severity of the disease and/or the duration. In cases of severe anemia
where the hemoglobin typically falls below 8 gm/dL, blood transfusions are required to maintain normal body functions.
- Leukopenia or Low White Blood Cell Count: There are two main types of white cells in the blood, neutrophils
which are responsible for fighting bacterial infections, and lymphocytes which fight viral infections. The absolute
neutrophil count or ANC can be low in MDS patients. Normally this count ranges between 4,000 to 10,000/ul. In
severely neutropenic patients, this count may fall as low as 100/ul or even lower. Despite such a severe leukopenia,
most MDS patients are not as prone to repeated infections as other patients with, for example, chemotherapy induced
leukopenia for two main reasons. First, the decline in ANC is gradual in MDS so that the body has a chance to
re-adjust itself. Secondly, the neutrophils despite being low in the blood are most likely present in higher numbers
where they are needed; in tissues. This is the most common cytopenia to accompany anemia.
- Thrombocytopenia or Low Platelet Count: Normal platelet count ranges between 150,000 to 400,000/ul in the blood.
These cells are involved in the prevention of bleeding and may be low in MDS patients. Severe thrombocytopenia is
said to occur when the platelet count falls below 30,000/uL. Thrombocytopenia as an isolated sign of MDS is a rare
but definite form of presentation. Such patients cannot be technically classified as Refractory Anemia patients
since there is no anemia. A newer form of morphologic classification (WHO Classification) now identifies these cases
as Refractory Cytopenia with Multi-lineage Dysplasia or RCMD.
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Common Treatment Options
The course of the disease and response to therapy in MDS vary between patients. It is important to follow
patients, especially those with a new diagnosis with periodic blood counts and bone marrow examinations.
For newly diagnosed patients, we recommend weekly blood counts even if the disease appears to be a benign,
low risk form of MDS, so that a general idea about the expected rate of progression may be obtained in the
first few months of diagnosis.
For transfusion dependent patients, and those with higher risk disease it is best to obtain a weekly CBC with
differential. If the counts remain stable, then the weekly checks can be relaxed, and patients may get bi-monthly
counts. Such a regular follow-up will allow for detection of disease progression and transformation to acute
leukemia in a timely manner. At this point, experimental therapies could be contemplated or patients may be
referred to special Centers for therapy or transplant.
The Mechanistic View vs. the Organismic View of MDS
The mechanistic view suggests that the human body can be conceived of as a machine, made up of individual components.
This view implies that if something goes wrong with one part of the body, then attention to fixing the individual
problem would readjust the malfunction back to normal and alleviate the disease.
The organismic view calls for a more complex view of the human body because it takes into consideration the fact
that most organs in the body function in an inter-dependent manner through complex communication networks. In
other words, the disruption in the routine of one organ will affect the functions of another. As long as the
problem is limited to something very specific such as a broken bone, the mechanistic approach will work fine.
However, treatment of a diseased organ alone, that cooperates with other systems in the body in order to produce
its desired end results, may not be as successful.
According to this view, treatment of any diseased organ must take into account, the entire body and not just the
one diseased organ. This is especially true for the more chronic diseases where slowly progressive pathology in
one organ leads to readjustments and compromises by several others. MDS is a prime example of one such disease
as described below since it is less of a discrete event than an interminable condition in a majority of patients.
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