Myelodysplastic Syndrome (MDS)

What is Myelodysplastic Syndrome?
Myelodysplastic syndrome (MDS) is a disorder in which the bone marrow does not make blood cells appropriately and in great enough numbers. This results in low numbers of red blood cells, white blood cells, platelets or all three. MDS has a significant chance of changing to Acute Myeloid Leukemia (AML), depending on a set of known risk factors. MDS is a disease of older adults, with more than 80% of patients aged more than 60 years. Although it is difficult to determine the exact incidence, it is estimated that MDS affects between 12,000 and 20,000 people in the United States each year. The physicians at Rocky Mountain Cancer Centers (RMCC) and the Rocky Mountain Blood and Marrow Transplant Program (RMBMTP) are specialists in the care of patients with MDS. MDS may be called other names including myelodysplasia or myelodysplastic syndrome.

What causes MDS?
The exact cause of MDS is unknown. It is not contagious and is not inherited. It can occur without any identifiable predisposing factors (de novo) or may develop after a patient has been treated with chemotherapy or radiation for another disease (therapy related MDS). MDS can be linked to acquired genetic changes in 40-70% of de novo MDS and 95% of therapy related MDS. Deletions of the long arms of chromosome 5 or 7 are the most common chromosomal abnormalities.

How is MDS diagnosed?
Often, people with MDS do not have symptoms when they are diagnosed. A doctor may find MDS on a “routine” medical examination when low blood counts in one or more of the cell lines (red blood cells, white blood cells or platelets) are found in the blood. When patients do have symptoms from MDS, they are related to low blood counts. If patients have anemia (low red blood cells), they may feel fatigued or tire easily, feel short of breath or dizzy, or look pale. If patients have neutropenia (low white blood cells) they may have frequent or difficult to treat infections, fever or chills. If patients have thrombocytopenia (low platelets), they may have easy bleeding or bruising that may result in nosebleeds, gum bleeding, or blood in the urine or stool.
Doctors use tests that examine the blood and bone marrow to detect and diagnose MDS, including:

• physical examination and history
• complete blood count (CBC) to look at the numbers of red blood cells, white blood cells and platelets
• examination of the peripheral blood smear to check for presence of blast cells, number and kinds of white blood cells, number of platelets, and changes in the shape of blood cells
• bone marrow biopsy and aspirate to look for abnormal cells
• Specialized tests on the bone marrow, which may be critical for diagnosis and prognosis, include karyotype (cytogenetics), fluorescence in situ hybridization (FISH) analysis, and flow cytometry

Once MDS has been diagnosed, a physician will determine what type of MDS a patient has and what the International Prognostic Scoring System (IPSS) score is. There are many types of MDS, which behave differently and have a different prognosis (chance of recovery). The prognosis of MDS is best determined by the type of MDS with which the patient presents, as well as the IPSS score.

International Prognostic Scoring System (IPSS)

Prognostic Variable (Score)	0	0.5	1.0	1.5	2.0
Bone Marrow Blast (Percentage)	<5	5-10	--	11-20	21-30
Cytogenetics*	Good	Intermediate	Poor	--	--
Cytopenias (number of cell lines with low counts)	0-1	2-3	--	--	--

*Good = diploid, -y, del(5q), del(20q)
Poor = chromosome 7 abnormalities or complex karyotypes
Intermediate = all others

Prognosis

Score	IPSS Subgroup	Median Survival(Years)	Lifetime AML Evolution
0	Low	5.7	19%
0.5-1.0	Intermediate - 1	3.5	30%
1.5-2.0	Intermediate - 2	1.2	33%
>2.5	High	0.4	45%

What are the treatment options for MDS?
Treatment options are tailored for patients based on disease risk (IPSS score), the severity of the blood counts and what kind of health condition the patient is in.

• Supportive careoptions are appropriate for many patients and include red blood cell and platelet transfusions, as well as treating other complications such as infections or secondary iron overload. Growth factor medications such as erythropoietin (Procrit), darbepoietin (Aranesp), or filgrastim (Neupogen) may help treat low blood counts.
• Chemotherapy or immune modulation should be considered in higher stage patients who often require blood or platelet transfusions and have a more aggressive disease. These agents include thalidomide, 5-azacytidine (Vidaza®), arsenic trioxide (Trisenox®), lenalidomide (Revlimid®), decitabine (Dacogen™), and antithymocyte globulin (ATG) ± cyclosporine.
• Acute leukemia type inductions are appropriate for better performance status patients with higher blast counts and higher risk disease
• Referral for allogeneic stem cell transplantation is indicated for selected higher risk patients.

The only curative treatment for MDS is allogeneic, or donor, stem cell transplant (SCT). Because of the risk of complications and death, allogeneic transplantation is generally limited to higher risk and younger patients. The physicians at the Rocky Mountain Blood and Marrow Transplant Program are willing to discuss all of these treatment options, including stem cell transplant, with you or with your referring physician.