About Myelodysplastic Syndromes (MDS)

MDS is a group of disorders where your bone marrow does not work well, and the blood-forming stem cells in your bone marrow fail to make enough healthy blood cells. People with MDS can lack the right amount of red blood cells, white blood cells, and platelets (the small cells that help blood to clot).

The disease happens because the bone marrow cells do not develop into mature blood cells. Instead, these blood cells stay within the bone marrow in an immature state. The symptoms and the course of MDS may vary greatly from person to person. These differences depend on which blood cells are affected.

All people with MDS have two things in common:

• They have a low blood cell count for at least 1 blood cell type. This is called cytopenia.
• Their bone marrow and blood contain blood cells with an abnormal shape, size, or look.
  

What does the term "myelodysplastic" actually mean?
Myelo = blood cells
Dysplastic = abnormal development or growth
So, when you have myelodysplastic syndrome, this means that your blood cells have an unusual shape and that they have abnormal growth.

Who develops MDS?

While the exact number of people who have MDS is not known, about 10,300 new cases were reported in the U.S. in 2003. This number was taken from data collected by the Surveillance, Epidemiology, and End Results (SEER) Program of the Centers for Disease Control (CDC) and the National Cancer Institute (NCI). This program only started collecting data in 2001. The number of people may be higher than reported because some doctors are not yet aware of the need to report MDS cases to a national registry. Some doctors believe that there are as many as 12,000 to 15,000 new MDS cases each year in the U.S.
We know that people diagnosed with MDS are:

• More often men than women
• Most often age 60 or older; the average age at diagnosis is 71
• Most often white; Native Americans, African-Americans, Inuits, Asians, and Pacific Islanders are least likely to get MDS.
  

What causes MDS?

Most of the time, doctors don't know the exact cause of MDS. These cases are called de novo MDS. We do know that certain lifestyle factors are linked to MDS.
You are more likely to develop MDS if you have:

• Been a smoker
• Been heavily exposed to certain chemicals, such as benzene
• Had chemotherapy or radiation treatments. These can cause treatment-related or secondary MDS. Treatment-related MDS is often severe and can be more difficult to treat than de novo MDS.
  

MDS cannot be passed down through the genes from parent to child and it cannot be passed through germs from person to person.

How is MDS Diagnosed?

MDS is a complex disease. So diagnosing it is a complex process. Doctors use a number of tools to figure out exactly what type of MDS you have.

Doing a Medical History

To understand what is causing your symptoms and low blood counts, your doctor will take a detailed medical history. Your doctor may ask you questions like the following:

• What are your symptoms?
• Have you been exposed to harmful chemicals, such as benzene, that have been linked to MDS?
• Are you a smoker or have you been a smoker?
• Have you had chemotherapy or radiation treatments in the past?
  

Providing your doctor a detailed health history helps your doctor give you an accurate diagnosis.

Getting Lab Work

When trying to figure out the cause of your symptoms, your doctor will ask for samples of your blood and bone marrow. These samples will be used in a number of tests.

About Blood Tests
The tests on your blood help your doctor find out what type of MDS you have. Some of the results can be confusing. This section explains your blood test results. Compare this section with the results of your blood work. It can help you better understand the lab report.

One important test is a complete blood count or CBC for short. The CBC measures the number of each blood cell type in your blood sample. If the CBC shows a low number of red blood cells, white blood cells, or platelets, your doctor may look at the cells under a microscope. This is called a blood smear, and it shows whether any red blood cells are not normal.

Your doctor will ask you to get a CBC, and possibly other blood tests, on a regular basis. This will allow your doctor to know if your blood counts are high or low and if they have changed from the last time you had a CBC. If your blood counts are abnormal or have changed, your doctor may try to find out why.

Learn more about the CBC test.

Other blood tests

Your doctor may order other blood tests after getting results from your CBC.
 
EPO level
EPO, or erythropoietin, is a protein made by your kidneys. It is created in response to low oxygen levels in the body - in other words, in response to anemia. EPO causes your bone marrow to make more red blood cells. A shortage of EPO can also cause anemia. A low EPO level may be a sign of a problem other than MDS, or it may make anemia worse in people who have MDS.

Iron level
If you have anemia, your doctor may also check the level of iron in your blood. A shortage of iron can cause anemia.

Vitamin B12 and folate levels
If your red blood cells have an abnormal shape, size, or look, your doctor will check the levels of vitamin B12 and folate in your blood. A shortage of these vitamins can cause dysplasia, or cells that are not normal, and this can lead to anemia.

About Bone Marrow Tests
Bone marrow tests are done for several reasons. Most likely, your doctor examined your bone marrow to confirm you have MDS. The doctor may also do a bone marrow exam now and again to find out if your MDS has stayed the same, improved, or worsened since the last exam.
The bone marrow test shows:

1. Exactly what types and amounts of cells your marrow is making
2. Levels of bone marrow blasts (immature white blood cells); if more than 5 out of every 100 white blood cells in your bone marrow is a blast cell, this is not normal
3. Damaged chromosomes (DNA) in the cells of your bone marrow. These are called cytogenetic (sie-toe-juh-NEH-tik) abnormalities. Some chromosome abnormalities are linked to specific MDS sub-types
   

Learn more about the process of getting a bone marrow test.

What are blasts?

When speaking about MDS, blasts are very young white blood cells. In normal bone marrow, no more than 5 out of 100 white cells are blasts. But people with MDS may have too many blasts in their bone marrow.

The number of blasts in the bone marrow is used to define how severe your MDS is:

• If less than 5 out of 100 white cells in your bone marrow are blasts, you have lower-risk MDS.
• If between 5 out of 100 and 19 out of 100 white cells in your bone marrow are blasts, you have higher-risk MDS.
• If 20 or more out of 100 white cells in your bone marrow are blasts, you have AML or acute myelogenous leukemia. About 30 out of 100 patients diagnosed with MDS will eventually have AML.
  

What are the symptoms of MDS?

The symptoms of MDS may vary greatly from person to person. The symptoms depend on what blood cells are affected and how low the blood counts have fallen. A person with MDS can have any of the following:

• Low Red Blood Cell Count: A low red blood cell count is called anemia. Red blood cells carry oxygen from your lungs to the rest of your body. A low red blood cell count causes fatigue and tiredness.
• Low White Blood Cell Count: A low white blood cell count is called neutropenia. White blood cells fight infections in the body by attacking and killing bacteria and viruses. A low white blood cell count can increase the risk for infections.
• Low Platelet Count: A low platelet count is called thrombocytopenia. Platelets help blood to clot and stop bleeding. A low platelet count can lead to bleeding problems and cause you to bruise easily.
  

If your MDS is in its early stages and your blood counts are not too low yet, you may have only mild symptoms. If your blood counts are very low, you will have more symptoms.

Lean more about the possible symptoms of low blood counts.

What are the types of MDS?

Before 1976, the term "MDS" didn't exist. Doctors and scientists used other names for what we now call MDS. At that time, there was no standard way to split MDS into subtypes.

In 1976, scientists came out with the first system for classifying MDS into subtypes. This system is called the French-American-British or FAB system. It is based on how blood and bone marrow cells look.
 
In 1997, the International Prognostic Scoring System or IPSS was launched. This system turns patient data into a score. The score tells how quickly an MDS case is likely to progress and helps predict what may happen with the patient's MDS in the future.

In 1999, the World Health Organization, or WHO, published a new classification system. This classification system was then revised in 2008. Its goal was to be more specific than the FAB in describing subtypes and in predicting what will happen to patients. The system is based on patient data from around the world and on the most up-to-date knowledge of MDS.

French American British (FAB) Classification System
Even though the newer WHO system updated the FAB system, the FAB system is still used by some doctors today.

The FAB system is based on four main factors:

• The percentage of blast cells in the bone marrow
• The percentage of peripheral blood blasts
• The percentage of red blood cell precursors with abnormal iron deposits called ring sideroblasts
• The percentage of monocytes in the blood
  

The FAB system divides MDS into 5 subtypes. These subtypes include:

1. Refractory anemia, also called RA
2. Refractory anemia with ring sideroblasts, also called RARS
3. Refractory anemia with excess blasts, also called RAEB
4. Refractory anemia with excess blasts in transition, also called RAEB-t
5. Chronic Myelomonocytic Leukemia, or CMML
   

MDS Subtype (FAB Classification System)	Blood Findings	Bone Marrow Findings
RA (Refractory Anemia)	Less than 1% blasts	Less than 5% blasts
RARS (Refractory Anemia with Ring Sideroblasts	Less than 1% blasts	Less than 5% blasts More than 15% of young red blood cells in marrow contain ring-shaped iron deposits called ring sideroblasts
RAEB (Refractory Anemia with Excess Blasts in Transmission) Note: Now called AML (acute myelogenous leukemia)	Less than 5% blasts At least 2 cytopenias (low blood cell counts)	5% to 20% blasts
RAEB-t (Refractory Anemia with Excess Blasts in Transformation)	More than 5% Note: At least 2 cytopenias (low blood cell counts)	21% - 30% blasts
CMMA (chronic myelomonocytic Leukemia)	Less than 5% More than 1,000 monocytes per cubic millimeter of blood	5% - 20% blasts

WHO (World Health Organization) Classification System

The WHO classification system builds and expands on the older FAB system. It divides MDS into seven subtypes based on tests of the blood and bone marrow. These seven subtypes include:

1. Refractory cytopenia with unilineage dysplasia or RCUD; there are three subtypes of RCUD:
   a.    refractory anemia or RA
   b.    refractory neutropenia or RN
   c.    refractory thrombocytopenia or RT
2. Refractory anemia with ring sideroblasts or RARS
3. Refractory cytopenia with multilineage dysplasia or RCMD
4. Refractory anemia with excess blasts type 1 or RAEB-1
   
5. Refractory anemia with excess blasts type 2 or RAEB-2
6. MDS with isolated deletion 5q 
7. MDS unclassified
   

MDS Subtype	Blood Findings	Bone Marrow Findings
RCUD (Refractory Cytopenia with Unilineage Dysplasia)	One low blood cell count (cytopenia) Has 3 subtypes: low red cell counts is called refractory anemia or RA low white cell count is called refractory neutropenia or RN low platelet count is called refractory neutropenia or RN	Less than 5% young white blood cells called blasts Little or no dysplasia
RARS (Refractory Anemia with Ring Sideroblasts)	Low red blood cell count that can't be treated with iron or vitamins	More than 15% red blood cells that contain ring-shaped iron deposits called ring sideroblasts
RCMD (Refractory Cytopenia with Multilineage Dysplasia)	Low white blood cell count (neutropenia) or low platelet count (thrombocytopenia)	Dysplasia in more than 1 cell type Less than 5% blasts, or less than 15% ringed sideroblasts Note: In patients with more than 15% ringed sideroblasts, the subtype is called RCMD_RS
RAEB-1 (Refractory Anemia with Excess Blasts)	The same as refractory anemia	5% tp 9% blasts in marrow Normal number of blasts in blood
RAEB-2 (Refractory Anemia with Excess Blasts 2)	Similar to  refractory anemia and RAEB-1	10% to 19% blasts in marrow
MDS with isolated deletion 5q	The same as refractory anemia, plus normal or high platelet count	Deletion of chromosome 5q, with no other chromosome abnormality
Unclassified MDS	Low count for wither platelets or white blood cells	Unusual features, such as scarring (fibrosis) of the bone marrow Note: Just 1% to 2% of MDS patients have this subtype

The older FAB system is a bit different than the newer WHO classification system. The WHO system made the following changes to the FAB system:

• Added isolated deletion 5q Syndrome and Unclassified MDS
• Created the category of RCUD (refractory cytopenia with unilineage dysplasia)
• Created a category called RCMD (refractory cytopenia with multilineage cytopenia)
• Split RAEB-t into 2 subtypes depending on the number of blast cells present in the bone marrow
• Reclassified Chronic Myelomonocytic Leukemia or CMML into a new group of diseases known as MDS/MPD. CMML used to be considered a kind of MDS
  

International Prognostic Scoring System (IPSS)

The IPSS gives each patient a score to help their doctor understand how quickly their MDS is progressing and what is likely to happen to their disease over time. The score is based on several factors that are linked to MDS. They are:

• Percentage of blasts in the bone marrow
• Changes in cell chromosomes, also called cytogenetics 
• Low blood cell counts or cytopenias
  

Each factor gets a score. Together, the scores tell which risk groups you fall into.

Your IPSS score helps your doctor to answer the following questions:

• How severe is your case of MDS?
• How likely is your case to become acute myeloid leukemia or AML if treated only with supportive care?
• How long are you likely to live if you are treated only with supportive care?

Factor	Value	IPSS Score
Blasts in bone marrow	less than 5% 5% to 10% 11% - 20% 21% - 30%	0 0.5 1.5 2.0
Cell DNA changes (cytogenics)	Good Intermediate Poor	0 0.5 2.0
Low blood counts or cytopenias	0 or 1 cytopenia 2 or 3 cytopenias	0 0.5

Using the IPSS, a patient is given a score between 0 and 3.0. A patient can be put into one of four risk groups, two lower-risk and two higher-risk. Scores of less than 1.5 are considered lower-risk.

This score tells you what risk group you fall into. For example:

• If your IPSS score is 0, you are in the low-risk group
• If your IPSS score is 0.5 to 1, you are in the intermediate-1 risk group
• If your IPSS score is 1.5 to 2, you are in the intermediate-2 risk group
  
• If your IPSS score is more than 2.0, you are in the high-risk group

Learn about Treatments for MDS.

__________________________

Order an AA&MDSIF information packet containing detailed information about MDS and its treatment.

For more in-depth information on MDS and its treatment you can also visit our Online Learning Center and view webcasts by some of the leading medical experts on MDS.
_________________________
Last updated May 2010