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The MDS are characterized by abnormal bone marrow and blood cell morphology.
Megaloblastic erythroid hyperplasia with macrocytic anemia, which is associated with
normal vitamin B12 and folate levels, is frequently observed. Circulating granulocytes are
frequently severely reduced, often hypogranular or hypergranular, and may display the
acquired pseudo-Pelger-Hut abnormality. Early, abnormal myeloid progenitors are
identified in the marrow in varying percentages, depending on the type of
myelodysplastic syndrome. Abnormally small megakaryocytes (micromegakaryocytes)
may be seen in the marrow and hypogranular or giant platelets may appear in the
blood.
The MDS occur predominantly in older patients (usually >60 years), though patients as
young as 2 years have been reported. Anemia, bleeding, easy bruising, and fatigue are
common initial findings. Splenomegaly or hepatosplenomegaly may occasionally be
present in association with an overlapping myeloproliferative disorder. Approximately
50% of the patients have a detectable cytogenetic abnormality, most commonly a
deletion of all or part of chromosome 5 or 7, or trisomy 8.Although the bone marrow is
usually hypercellular at diagnosis, 15% to 20% of patients present with a hypoplastic
bone marrow.Hypoplastic myelodysplastic patients tend to have profound cytopenias
and may respond more frequently to immunosuppressive therapy.
A variety of risk classification systems have been developed to predict the overall
survival of patients with MDS and the evolution from MDS to AML. These classification
systems include the French-American-British classification, the Bournemouth score, the
Sanz score, the Lille score, and the World Health Organization classification. Clinical
variables in these systems have included bone marrow and blood myeloblast
percentage, specific cytopenias, age, lactate dehydrogenase level, and bone marrow
cytogenetic pattern.
An International MDS Risk Analysis Workshop was convened, and the clinical data from
816 patients with primary MDS from seven previously reported studies, which used
independent risk-based prognostic systems, were combined and collated.The combined
data were analyzed centrally, and a global analysis was performed, which formed the
basis of a new prognostic system called the International Prognostic Scoring System for
MDS. In multivariate analyses, significant predictors for both survival and AML evolution
included bone marrow blast percentage, number of peripheral blood cytopenias, and
cytogenetic subgroup. The data are used to assign MDS patients a score, which
stratifies patients into one of four risk groups: low risk, intermediate-1, intermediate-2,
and high risk. The time for the development of AML in the risk groups was 9.4 years, 3.3
years, 1.1 years, and 0.2 years, respectively. Median survival for the groups was 5.7
years, 3.5 years, 1.2 years, and 0.4 years, respectively. The system has been
incorporated into clinical trial design for MDS.
CLASSIFICATION
Cellular Classification
Work on the French-American-British (FAB) classification scheme for the MDS began in
the late 1970s under the direction of the French-American-British Cooperative Group
(see table below). The version published in 1982 was the first diagnostic classification
scheme to clearly and reproducibly distinguish MDS from acute myelogenous leukemia
(AML). According to the FAB scheme, the percentage of bone marrow blasts required
for the diagnosis of MDS ranges from less than 5% to as much as 29%. The FAB
scheme is still frequently used by clinicians to categorize the MDS.
Several weaknesses were identified in the FAB classification of MDS. The inclusion of
chronic myelomonocytic leukemia (CMML) was problematic; CMML is a disease that
combines features of both MDS and chronic myeloproliferative disorders. In addition,
the FAB classification did not take cytogenetic findings into account. For example, the
cytogenetically defined MDS subtype del(5q) represents a distinct clinical entity.
In 1997, under the auspices of the World Health Organization (WHO), a working group
of pathologists and clinicians from around the world agreed to a new cellular
classification scheme for hematopoietic and lymphoid malignancies. Significant changes
to the FAB classification of these malignancies were made. For the classification of
MDS, the new WHO classification lowered the threshold to 20% for the number of
myeloblasts required to make the diagnosis of AML. This arbitrary threshold value for
blast percentage eliminated the cellular type, refractory anemia with excess blasts in
transformation (RAEB-t), found in the FAB classification scheme. In the WHO cellular
classification scheme, RAEB-t is no longer considered a distinct clinicopathologic entity;
instead, RAEB-t is included within the broader category, AML with multilineage
dysplasia, and identified as AML with multilineage dysplasia following a myelodysplastic
syndrome.
The elimination of RAEB-t from the WHO cellular classification scheme met some
resistance. Some have argued that the biology of RAEB-t is distinct from AML and
should be retained as a diagnostic category of MDS. Others have emphasized the
similar prognoses and responses to treatment for RAEB-t and AML with trilineage
dysplasia.The diagnosis of AML, which is based upon a threshold of 20% bone marrow
or peripheral blood myeloblasts, does not represent a therapeutic mandate. The
decision to treat must include other factors, such as patient age, prior history of MDS,
clinical findings, disease progression, and most importantly, patient preference, in
addition to the blast count. The same factors influence treatment options for patients
with 30% or more myeloblasts in the blood or marrow.
Myelodysplastic Syndromes:
Comparison of the FAB and WHO
Classifications WHO (1997)
Enlarge
FAB (1982)
Refractory anemia with excess blasts Refractory anemia with excess blasts
Refractory anemia with excess blasts Acute Myeloid Leukemia identified as, AML
in transformation with multilineage dysplasia following a
myelodysplastic syndrome
MDS cellular types and subtypes in either cellular classification scheme have different
degrees of disordered hematopoiesis, frequencies of transformation to acute leukemia,
and prognoses. All WHO cellular types and subtypes and the FAB cellular type, RAEB-t,
are described in detail below.
In patients with RARS, the blood and marrow are identical to those in patients with RA,
except that at least 15% of marrow red cell precursors are ringed sideroblasts.
Approximately 10% to 12% of patients present with this type, and prognosis is identical
to that of RA. Approximately 1% to 2% of RARS evolve to AML.
The cellular subtype, MDS-U, lacks findings appropriate for classification as RA, RARS,
RCMD or RAEB. Blasts in the blood and bone marrow are not increased.
This MDS cellular subtype, the 5q- syndrome, is associated with an isolated del(5q)
cytogenetic abnormality. Blasts in both blood and bone marrow are less than 5%. This
subtype is associated with a long survival. Karyotypic evolution is uncommon. Additional
cytogenetic abnormalities may be associated with a more aggressive MDS cellular
subtype or may evolve to acute myeloid leukemia.
Clinical Classification
The clinical classification of MDS is used to determine disease prognosis and treatment
strategy, and to define entry requirements for many MDS clinical trials.
Tobacco smoke.
Ionizing radiation.
Heavy metals.
Herbicides.
Pesticides.
Fertilizers.
Exhaust gases.
Nitro-organic explosives.
Alkylating agents.
Marrow-damaging agents used in cancer chemotherapy.
Patients with documented exposure to such agents are referred to as having secondary
MDS or treatment-related MDS and constitute as many as 30% of all patients with MDS.
Secondary MDS typically has a poorer prognosis than does de novo MDS.
Previously treated MDS are de novo or secondary cases of MDS that have progressed
despite previous treatment and, in many cases, are receiving additional treatment.
SYMPTOMS OF MYELODYSPLASIA
The list of signs and symptoms mentioned in various sources for Myelodysplastic
syndromes includes the 26 symptoms listed below:
Fatigue
Lightheadedness
Fever
Bruising
Splenomegaly
Angina pain
Shortness of breath
Epistaxis
Cytopenia
Bleeding
Frequent infections
Anemia
Fatigue
Exertional dyspnea
Low blood platelet level
Petechiae
Mucosal bleeding
Gastrointestinal bleeding
Enlarged spleen
Thrombocytopenia
Leucopenia
Poikilocytosis
Breathlessness
Reduced white blood cell level
Cytopenia
Low blood cell count
DIAGNOSIS
Physical exam and history: An exam of the body to check general signs of health,
including checking for signs of disease, such as lumps or anything else that seems
unusual. A history of the patients health habits and past illnesses and treatments
will also be taken.
Complete blood count (CBC) with differential: A procedure in which a sample of
blood is drawn and checked for the following:
Enlarge
Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a
small piece of bone by inserting a hollow needle into the hipbone or breastbone. A
pathologist views the bone marrow, blood, and bone under a microscope to look for
abnormal cells.
Bone marrow aspiration and biopsy.
After a small area of skin is numbed, a
Jamshidi needle (a long, hollow needle)
is inserted into the patients hip bone.
Samples of blood, bone, and bone
marrow are removed for examination
under a microscope.
Refractory anemia: There are too few red blood cells in the blood and the
patient has anemia. The number of white blood cells and platelets is normal.
Refractory anemia with ringed sideroblasts: There are too few red blood cells
in the blood and the patient has anemia. The red blood cells have too much iron.
The number of white blood cells and platelets is normal.
Refractory anemia with excess blasts: There are too few red blood cells in the
blood and the patient has anemia. Five percent to 19% of the cells in the bone
marrow are blasts and there are a normal number of blasts found in the blood.
There also may be changes to the white blood cells and platelets. Refractory
anemia with excess blasts may progress to acute myeloid leukemia.
Refractory anemia with excess blasts in transformation: There are too few
red blood cells, white blood cells, and platelets in the blood and the patient has
anemia. Twenty percent to 30% of the cells in the bone marrow are blasts and
more than 5% of the cells in the blood are blasts. Refractory anemia with excess
blasts in transformation is sometimes called acute myeloid leukemia.
TREATMENT
There are different types of treatment for patients with myelodysplastic
syndromes.
Different types of treatments are available for patients with myelodysplastic syndromes.
Some treatments are standard (the currently used treatment), and some are being
tested in clinical trials. A treatment clinical trial is a research study meant to help
improve current treatments or obtain information on new treatments for patients with a
myelodysplastic syndrome. When clinical trials show that a new treatment is better than
the standard treatment, the new treatment may become the standard treatment.
Patients may want to think about taking part in a clinical trial. Some clinical trials are
open only to patients who have not started treatment.
Treatment options for patients with myelodysplastic syndromes range from supportive
care that helps relieve symptoms to aggressive treatment that may slow or prevent
progression of the disease.
Problems caused by low blood cell counts, such as fatigue and infections, may be
treated with transfusions of blood products or the use of growth factors.
Chemotherapy may be used to delay progression of the disease. Other drug therapy
may be used to lessen the need for transfusions. Certain patients may benefit from
aggressive treatment with chemotherapy followed by stem cell transplant using stem
cells from a donor.
Supportive care
Supportive care is given to lessen the problems caused by the disease or its treatment.
Supportive care may include the following:
Transfusion therapy
Transfusion therapy (blood transfusion) is a method of giving red blood cells, white
blood cells, or platelets to replace blood cells destroyed by disease or treatment.
Patients who receive frequent red blood cell transfusions may have their tissues
and organs damaged from the buildup of extra iron. Iron chelation therapy is a
treatment that uses drugs that attach to the extra iron. The drug and the iron are
removed from the body in the urine.
Platelet transfusions are usually given when the patient is bleeding or is having a
procedure that may cause bleeding.
Drug therapy
Deferoxamine may be used to treat the build-up of too much iron in the blood of
patients receiving blood transfusions. It is sometimes given with vitamin C.
Lenalidomide may be used to lessen the need for transfusions in patients who have
myelodysplastic syndrome caused by a specific chromosome change.
Antithymocyte globulin (ATG) may also be used to lessen the need for transfusions
in patients with a certain form of myelodysplastic syndrome.
1. http://www.cancer.gov/cancertopics/pdq/treatment/myelodysplastic/HealthProfess
ional/page2
2. http://www.wrongdiagnosis.com/medical/myelodysplasia.htm
3. http://www.wrongdiagnosis.com/m/myelodysplastic_syndromes/symptoms.htm
4. http://www.cancer.gov/cancertopics/pdq/treatment/myelodysplastic/Patient/page3