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What is Myelodysplastic Syndrome (MDS)?

Myelodysplastic Syndrome (MDS)is the term used to describe a group of closely related conditions whose origin is hematopoietic stem cells (immature cells) of bone marrow from which all different types of blood cells develop. Myelodysplastic means myelo = bone marrow and blood cells, dysplatic = abnormal looking.

Development of Myelodisplastic Syndrome:

A hematopoietic stem cell may mature to become either a lymphoid stem cell or a myeloid stem cell. The myeloid stem cell develops into any one of the three types of blood cells i.e. white blood cells/WBCs/leucocytes (combat infection) or red blood cells/RBCs/erythrocytes (oxygen carriers) or blood platelets (stop or prevent bleeding) whereas the lymphoid stem cell becomes a white blood cell.
Blood cell lineage

Myelodysplastic Syndrome occurs when the hematopoietic stem cells do not mature to become erythrocytes or leucocytes or platelets. In other words the number of immature cells or blasts increases rapidly. These blast cells die before reaching maturity (transforming into either of the blood cells), just before they enter the bloodstream. Even if they enter the blood, due to their abnormality their functioning is not normal. This in turn results in decreased circulation levels of matured blood cell types such as red blood cells (anemia), platelets (thrombocytopenia) and white blood cells in the blood.

People with MDS have low blood count when compared to a normal person. The reduction in the number of blood cell types (cytopenia) may lead to infections due to decreased number of white blood cells (combat infections) or anemia due to lack of red blood cells/oxygen carriers or bleeding and bruising due to low levels of blood platelets. Gradually normal white blood cells and red blood cells are replaced by increasing blast cells in the bone marrow leading to Acute Myeloid Leukemia (AML).

Blast cells comprise of less than 5% of the cells in the bone marrow in normal conditions. But, in people suffering from MDS their number is usually more than 5%. The severity of the syndrome can be determined by the percentage of blast cells present in the bone marrow. The higher the number of these cells, the greater is the severity. If an individual has more than 20% of blast cells he/she is most likely to be diagnosed with acute myelogenous (or myeloid) leukemia (AML).

Incidence of MDS:

MDS falls under the category of rare syndromes. In the USA, between 10,000 and 15,000 people are diagnosed with this condition every year according to an estimate by American cancer society. Among them, almost 90% are over 60 and 10-20% people with MDS gradually develop AML.

Types of Myelodysplastic Syndrome:

Based on the types of blood cells involved, MDS is divided into following subtypes. These include:

  1. Refractory anemia – In this type of anemia, red blood cells are low in number in the blood. White blood cells and platelets do not show any variation in number.
  2. Refractory anemia with excessive blast cells – An individual suffering from this is anemic with reduced number of erythrocytes in the blood. Moreover, the number of blast cells remains normal in the bloodstream, but their population is between 5 and 19% of the total cells in the bone marrow. Changes in platelets and leucocytes may also be seen. This type of anemia may most probably progress to acute myeloid leukemia (AML).
  3. Refractory anemia with ringed sideroblasts – White blood cell and platelet numbers remain normal. Patient is anemic due to reduced number of RBCs. Also, in this condition the red blood cells have abnormal iron levels (ringed sideroblasts).
  4. Refractory cytopenia with multilineage dysplasia – In this condition any 2 blood cell types out of the 3 are less in number than their normal count. Blast cells constitute less than 1% of the cell population in the bloodstream and less than 5% in the bone marrow.
  5. Refractory anemia with excessive blast cells in transformation – This condition is sometimes referred to as acute myeloid leukemia (AML). Patient is anemic with a very low number of red blood cells, white blood cells and platelets. Blast cells increase in numbers rapidly constituting nearly 20 – 30% of the cell population in the bone marrow and more than 5% of the cell population in the bloodstream.
  6. MDS associated with del (5q) chromosome abnormality – People with this condition have low number of red blood cells and these cells are characterized by defect in a chromosome.
  7. Unclassified Myelodysplastic Syndrome – This condition is characterized by reduced number of one cell type among 3. Also, either platelets or white blood cells appear abnormal when observed under a microscope.

Causes of Myelodysplastic Syndrome:

Based on the cause of this condition, it has been divided into 2 categories. These include:

  1. Primary/ de novo/ Myelodysplastic Syndrome with no known cause – As the name indicates, the cause is not known in people suffering from this condition. This type of syndrome may be treated with much ease when compared to the ones whose cause is known. Majority of people are affected by primary MDS.
  2. Secondary/ Treatment related Myelodysplastic Syndrome – This is usually caused by radiotherapy and chemotherapy taken for previously diagnosed cancers such as myeloma, breast cancer, lymphoma etc. Moreover, repeated and continuous exposure to benzene (damages the DNA of stem cells) also leads to this condition. People get exposed to this chemical through smoking cigarettes and working in some industries. Not all people exposed to benzene and/or chemotherapy develops this syndrome. Scientists attribute the development of MDS in some and not in others to the inherited genes that have a very limited ability to detoxify the toxic chemicals.

Symptoms of Myelodysplastic Syndrome:

There is no specific set of symptoms related to MDS. The symptoms experienced could be common in some other conditions. Therefore it is always advisable to consult a doctor if any of the following symptoms begin to show up.

  • Shortness of breath.
  • Lightheadedness and headache.
  • Extreme paleness due to anemia.
  • Feeling tired or weak with less activity.
  • Frequent infections in the throat, lungs, skin and sinuses.
  • Infections in war or mouth or teeth due to a condition known as neutropenia, where neutrophils (a type of white blood cells) are less in number.
  • Fever.
  • Frequent nosebleeds.
  • Easy bleeding or bruising.
  • Pinpoint red spots beneath the skin caused by bleeding known as Petechiae.
  • Skin rashes due to thrombocytopenia (shortage of blood platelets).
  • Weight loss.

Risk Factors:

Risk factor is the term used to describe a person’s likelihood to develop a particular disease due to the presence of certain traits. Risk factors of MDS include:

  • Exposure to heavy metals such as mercury or lead.
  • People above 60 years of age.
  • Exposure to some pesticides, tobacco smoke etc.
  • White skin.
  • Men are more prone to the syndrome than women.

Diagnosing MDS:

It is a very difficult task to diagnose this syndrome as the symptoms associated with MDS could also appear in several other malignancies. Some blood and bone marrow tests are useful to detect the condition.

Blood Tests:

  • Complete Blood Count (CBC) – This involves taking blood from the patient and counting the number of red blood cells, platelets and white blood cells. In addition, hemoglobin content is also checked.
  • Peripheral Blood Smear – Blood sample taken from the patient is examined for changes in the size, shape, number and type of blood cells. Excess amount of iron in RBCs can also be detected using this procedure.

Bone marrow tests:

Bone marrow aspiration for Myelodisplastic SyndromeBone marrow samples are collected and various tests performed on them to diagnose the condition. Bone marrow biopsy involves the extraction of a small piece of bone, blood and bone marrow from hipbone using a hollow needle. Similarly, bone marrow aspirate (liquid from the bone marrow) is obtained.

Several tests are performed on the samples taken by the above mentioned process. These tests act as tools in confirming the diagnosis of MDS.

The following tests are performed on bone marrow samples.

  • Molecular Genetic Analysis – This is done to determine the genetic traits of the bone marrow cells by conducting sensitive RNA and DNA tests.
  • Cytogenetic Studies – They help in determining chromosomal abnormalities if any in the bone marrow cells. Nearly half of the patients suffering from MDS have been detected with changes in chromosomes specifically on chromosomes 5, 7, 8 and 20.
  • Flow Cytometry – Bone marrow cells are passed through a laser beam to check if their development is normal and to get the blast cell count.
  • Histochemistry Analysis – Bone marrow cells are checked for any abnormalities by the doctors.

Treatment for Myelodysplastic Syndrome:

Options to treat this syndrome are mainly aimed at relieving symptoms and slowing down the progression of the disease. Before a patient can begin the treatment, factors such as age, overall health, severity of the condition, probability that he/she will be eligible to receive a stem cell transplant should be considered.

Current available options include supportive care to relieve symptoms in patients, who are at low risk including drug therapy, blood or growth factor transfusions for infections and fatigue, and rigorous treatments to slow down the progression of the disease.

Treatment strategies include:

  1. Supportive Care – The following therapies fall under this category and are aimed at reducing the symptoms of MDS.
    • Growth Factor Therapy – Growth factors are the substances that stimulate the production of blood cells. Erythropoietin (EPO) is a hormone that induces red blood cell production. “Erythropoietin-Stimulating Agents (ESAs)” are the red blood cell growth factors. The synthetic forms of EPO, Aranesp and Procrit are given in the form of injections to the patients.
    • Transfusion Therapy – Blood transfusion is a process of replacing destroyed blood cells with new white blood cells or red blood cells or platelets. Frequent blood transfusion may damage the organs and tissues in the body due to excess accumulation of iron. In such cases iron chelation therapy is given. This involves a drug that attaches itself to the extra iron. The combined part (drug+iron) passes out of body during urination. Blood platelet transfusion is usually given to the patients while undergoing a procedure that may lead to bleeding.
    • Drug Therapy – Antithymocyte globulin (ATG) is given to patients with a specific form of MSD to reduce the need for transfusions. Deferoxamine is used to treat the accumulated iron in the blood. Antibiotics are given to combat infections. Lenalidomide is the drug given to the patients to decrease the need of transfusions who are suffering from MSD due to changes in a specific chromosome.
  2. Chemotherapy – In MSD, this particular term is used to describe the treatment that involves drugs which stop the growth of blast cells (immature cells). In systemic chemotherapy, the drug is either injected into a muscle or vein or taken orally which travels through the bloodstream to reach the cancerous cell growths. Unlike systemic, regional chemotherapy involves the introduction of drug directly into the affected organ.
  3. Bone marrow harvest operation for Myelodisplastic Syndrome

  4. Stem Cell Transplantation – In this method, the damaged cells are replaced by stem cells. Immature blood cells or stem cells are extracted from the bone marrow or blood of a donor and are frozen. Soon after the chemotherapy (destroys the excess blast cells), stem cells are introduced into the patient’s body. They grow into new blood cells.

Because Myelodysplastic Syndrome is characterized by low blood cell counts, it is advisable to keep away from situations or conditions that may hamper the functioning of your immune system.

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