Table Of Content10/18/2011
Myelodysplastic Syndromes
Rami Komrokji, MD
Clinical Director
Malignant Hematology
Moffitt Cancer Center
Normal Blood and Bone Marrow
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What is MDS
• Myelodysplastic Syndromes (MDS) are a
group of diverse bone marrow disorders in
which the bone marrow does not produce
enough healthy blood cells.
What is MDS
• Myelodysplastic syndromes-
– Myelo- prefix means marrow
– Dysplasia-refers to the abnormal shape and appearance — or
morphology — of the blood cells.
– Syndromes means a set of symptoms that occur together.
• MDS has been known as ―smoldering leukemia,‖
―preleukemia‖ or ―oligoleukemia.‖
– These terms may be misleading by implying that MDS is only
problematic after it has evolved to AML.
– MDS can progress such that the abnormal blast cells take over
the marrow and the disease ―evolves‖ into AML.
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What is MDS
• MDS originates from mutations in a normal stem cell in the
marrow
• In MDS, the blood stem cells do not mature into healthy blood
cells. The immature blood cells do not function normally and either
die in the bone marrow or soon after they enter the blood.
• Normally, immature cells known as ―blasts‖ make up less than five
percent of all cells in the marrow. In Some MDS patients, blasts
comprise more than five percent of the cells.
• The number of blast cells from cases with lower proportions of
blast cells to cases with higher proportions of blast cells—is one of
the principal determinants of disease severity.
What is MDS
• Is MDS a ―cancer‖ ?
– MDS is a diagnosis of cancer.
– Cancer means that a mutation of a normal cell leads
to the development of cells that no longer behave
normally.
– MDS is spectrum of disorders
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How common is MDS
• One of the most common hematological
malignancies ―Blood cancers‖.
• At least 10,000 new cases in the united states
diagnosed every year.
• Majority of patients are above age of 60.
• Slightly more in males.
MDS incidence Rates in USA by Age and Gender
SEER & NAACR Databases
50
overall males females
40 36.3*
30
20.8
20
7.4
10
2.0
0.1 0.7
0
< 40 40-49 50-59 60-69 70-79 80+
Age at diagnosis (yrs)
Rollison and List et al, Blood 2008:112:41. * p for trend = 0.01
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What Causes MDS?
• The exact causes of MDS are unknown in
majority of patients.
• Senescence ―aging‖ of stem cells plays major
role in developing MDS.
• MDS may be ―primary‖ (also called ―de novo‖)
or ―secondary‖ (cases that arise following
treatment with chemotherapy and radiotherapy
for other cancers, such as lymphoma,
myeloma or breast cancer).
What Causes MDS?
• Repeated exposure to the chemical benzene—
which damages the DNA of normal stem
cells—is another predisposing factor in MDS
development.
– Benzene in cigarette smoke is now the most
common known cause of exposure to this toxin.
– Benzene is also found in certain industrial settings.
However, the stringent regulation of its use has
diminished benzene exposure in the workplace.
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What causes MDS
• There are no known food or agricultural products that
cause MDS.
• Alcohol consumed on a daily basis may lower red
blood cell and platelet counts, alcohol does not cause
MDS.
• No evidence exists to suggest that MDS is contagious
disease; thus, MDS cannot be transmitted to loved
ones.
• MDS is not inherited. In fact, it is a very rare occasion
when family members, including siblings, are
diagnosed with MDS.
What are the Symptoms of MDS?
• In the early stages of MDS patients may
experience no symptoms at all. A routine blood
test may reveal reduced blood counts.
• Patients with blood cell counts well below
normal, experience definite symptoms related
to low blood counts.
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ANEMIA = LOW RED CELL COUNT
• The majority of MDS patients are anemic.
• Anemic patients generally experience fatigue.
• Anemia varies in its severity:
– Mild anemia, patients may feel well or just slightly fatigued.
– Moderate anemia, almost all patients experience some fatigue,
which may be accompanied by heart palpitations, shortness of
breath, and pale skin.
– Severe anemia, almost all patients appear pale and report
chronic overwhelming fatigue and shortness of breath.
• Because severe anemia reduces blood flow to the
heart, older patients may be more likely to experience
cardiovascular symptoms, including chest pain.
NEUTROPENIA=LOW WHITE CELL COUNT
• A reduced white cell count lowers the body’s
resistance to bacterial infection.
• Patients may be susceptible to:
– skin infections
– sinus infections
– lung infections
– urinary tract infections
• Fever may accompany these infections.
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THROMBOCYTOPENIA=LOW PLATELET
COUNT
• Patients with thrombocytopenia have an
increased tendency to bruise and bleed even
after minor bumps and scrapes.
• Nosebleeds are common and patients often
experience bleeding of the gums, particularly
after dental work.
What Tests are used to diagnose MDS?
• Blood counts.
• Peripheral Blood smear
• Bone marrow aspirate and biopsy
• Cytogenetic Testing
• FISH
• Other tests ordered
– Vitamin b12 level
– Folate
– Iron and ferritin
– Serum erythropoietin level.
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Diagnosis of MDS
• An experienced hematopathologist should
examine the peripheral blood smear and bone
marrow.
• Diagnosis of MDS is made if
– Patient has persistent cytopenia.
– Demonstration of increased ―blasts‖.
– Demonstration of ―dysplasia‖.
– Demonstration of certain cytogenetic abnormalities.
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Cytologic Dysplasia:
Courtesy of Dr List and Bennett
Cytogenetics
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Description:10/18/2011 2 What is MDS •Myelodysplastic Syndromes (MDS) are a group of diverse bone marrow disorders in which the bone marrow does not produce
