Professional Documents
Culture Documents
Myelodysplastic Syndromes
Myelodysplastic Syndromes
Syndromes
History of MDS
Ecchymoses
Fatigue
Pallor
Ecchymoses/petechiae
Abnormal bleeding
Infection
MDS Etiology
Two etiologic categories of MDS:
1.) De Novo:
Associated with:
-benzene exposure (gasoline)
-cigarette smoking
-viruses -Fanconi’s anemia
80
60
40
20
0
RA RA RCMD RC RA RARS 5q-
EB-2 EB-1 MD-
RS
MDS Category
Prognostic Scoring
The International Myelodysplastic Syndrome Working
Group developed a scoring system based on 3 variables:
Cytopenia
0-1 2-3
International
Prognostic Scoring
System Data (IPSS)
Overall median survival was
5.7, 3.5, 1.2, and 0.4 years for
patients with IPSS scores of
zero (low risk), 0.5 to 1.0
(intermediate-1 risk), 1.5 to
2.0 (intermediate-2 risk), and
2.5 to 3.5 (high risk),
respectively.
Prognosis:
Median survival is 66 months
6% rate of progression to acute leukemia
Peripheral Smear -
Anisopoikilocytosis
Dyserythropoeisis on Bone Marrow
Aspirate
Megaloblastoid Change on Bone
Marrow Aspirate
Refractory Anemia with Ringed
Sideroblasts
RARS definition:
Dyplasia of the erythroid series only.
Clinically, anemia is refractory to hematinic
therapy
Myeloblasts < 5% in marrow, absent in blood
>15% ringed sideroblasts in marrow
No Auer rods
Other etiologies of ringed sideroblasts must be
excluded. These include:
– Anti- tuberculosis drugs
– Alcoholism
Refractory Anemia with Ringed
Sideroblasts
Epidemiology:
10-12% of MDS cases.
Older patients
Males > females
Morphology:
Dimorphic pattern on peripheral smears
– Majority RBC’s normochromic, 2nd population
hypochromic
Dyserythropoiesis with nuclear abnormalities
(megaloblastoid change)
Refractory Anemia with Ringed
Sideroblasts
Morphology (con’t.)
< 15% ringed sideroblasts (RS)
– RS = Erythroid precursor with ≥ 10 siderotic
granules encircling 1/3 or more of the
nucleus.
– If excess blasts present, this dictates
diagnosis, despite percentage of RS’s.
Refractory Anemia with Ringed
Sideroblasts
Genetics:
Clonal chromosomal abnormalities in
<10%; in fact, development of such an
abnormality should prompt reassessment of
diagnosis.
Prognosis:
Median survival 6 years (72 months)
1-2% rate of progression to acute leukemia
Dimorphic Red Cell Population
Ringed Sideroblasts
Ringed Sideroblasts
Megaloblastoid Change
Refractory Cytopenia with
Multilineage Dysplasia
RCMD definition:
Dyplasia in 10% or more of cells in 2 or
more myeloid lines.
Myeloblasts < 1% blasts in the blood and
< 5% in marrow.
No Auer rods
< 1 x 109/L monocytes in blood
Refractory Cytopenia with
Multilineage Dysplasia
Epidemiology:
24% of MDS cases.
Older patients
Morphology:
Neutrophil abnormalities may include:
– Hypogranulation
– Pseudo-Pelger-huet (hyposegmentation/barbells)
Megkaryocyte abnormalities may include
– Hypolobation -Micromegakaryocytes
Refractory Cytopenia with
Multilineage Dysplasia
Morphology (con’t.)
Erythroid abnormalities may include
nuclear abnormalities such as:
– megaloblastoid change -multilobation
– multinucleation
– In addition:
Erythroid presursors may be PAS positive
If >15% of erythroid precursors are ringed
sideroblasts, call = RCMD-RS
Refractory Cytopenia with
Multilineage Dysplasia
Genetics:
Clonal chromosomal abnormalities found in up to 50% of
RCMD and RCMD-RS cases. The abnormalities include:
– Trisomy 8 -del(7q) -del(5q)
– Monosomy 7 -Monosomy 5 -del(20q)
– Complex karyotypes
Prognosis:
Median survival 33 months
11% rate of progression to acute leukemia
RCMD and RCMD-RS = similar survival
Complex karyotypes = worse survival (10-18 months)
Pelgeroid (pseudo Pelger-Huet)
Neutrophil
Pelgeroid (pseudo Pelger-Huet)
Neutrophil
Dyserythropoiesis on Bone Marrow
Aspirate
Hypersegmented Neutrophil
Micromegakaryocyte
Refractory Anemia with Excess
Blasts
RAEB definition:
Refractory anemia with 5-19%
myeloblasts in the bone marrow.
– RAEB-1:
5-9% blasts in bone marrow and <5% blasts in
blood.
– RAEB-2:
10-19% blasts in the bone marrow
Auer rods present
Refractory Anemia with Excess
Blasts
Epidemiology: 40% of MDS cases.
Older patients (over 50 years)
Morphology:
Dysplasia of all three cell lines often present
Neutrophil abnormalities may include:
– Hypogranulation -hypersegmentation
– Pseudo-Pelger-huet (hyposegmentation/barbells)
– Pseudo Chediak-Higashi granules
Megkaryocyte abnormalities may include
– Hypolobation -Micromegakaryocytes
Refractory Anemia with Excess
Blasts
Morphology (con’t.)
Erythroid precursor abnormalities may include:
– Abnormal lobulation -megaloblastoid change
– Multinucleation
0-19% myeloblasts in the blood
5-19% in the marrow
Bone marrow:
– Usually hypercellular (10-15% hypocellular)
– Abnormal localization of immature precursors (ALIP) may be
present
Immunophenotype:
– Blasts express CD 13, CD33 or CD117
– The only MDS with a relevant phenotype
Refractory Anemia with Excess
Blasts
Genetics:
Clonal chromosomal abnormalities found in 30% - 50%
of RAEB cases. The abnormalities include:
– +8 – -5 – del(5q)
– -7 – del(7q) – Complex karyotypes
Prognosis:
Median survival, RAEB-1 = 18 months
Median survival, RAEB-2 = 10 months
RAEB-1 = 25% rate of progression to acute leukemia
RAEB-2 = 33% rate of progression to acute leukemia
Hypercellular Bone Marrow
Blasts and Hypogranulation
Myeloblast with Auer Rod
Chediak-Higashi-like Granules
Morphology:
BmBx usually hypercellular
Dyplastic megakaryocytes may be prominent
Myelodysplastic Syndrome,
Unclassifiable
Genetics:
May be normal, or clonal abnormalities the
same as those found in other MDS syndromes.
Prognosis:
Unknown
Occasionally defining characteristics develop.
Then case should be reclassified.
Myelodysplastic Syndrome Associated With
Isolated del(5q) Chromosome Abnormality
( 5q- Syndrome)
5q- syndrome definition:
MDS with an isolated del(5q)
<5% blasts in blood and bone marrow
Epidemiology:
Middle age to older women
Clinical Presentation:
Refractory anemia, often severe
Thrombocytosis may be present.
Myelodysplastic Syndrome Associated with
Isolated del(5q) Chromosome Abnormality
( 5q- Syndrome)
Morphology:
– Peripheral Smear:
Marked macrocytic anemia.
Slight leukopenia
Normal to elevated platelets
– BmBx:
Erythroid dysplasia, varying degrees
Small, hypolobated megakaryocytes
Scattered aggregates of small lymphocytes
Myelodysplastic Syndrome Associated with
Isolated del(5q) Chromosome Abnormality
( 5q- Syndrome)
Genetics:
Deletion between bands q31 and q 33 on
chromosome 5.
Size of deletion and breakpoints are variable.
Any additional cytogenetic abnormality excludes
placement in this category.
Prognosis:
Good = long survival
Those who develop more than 5% blasts may
have shorter survival
Hypolobated megakaryocytes
Myelodysplastic/myeloproliferative
diseases
WHO category consists of 4 entities
– Chronic myelomonocytic leukemia (CMML)
Formerly an MDS
– Atypical chronic myeloid leukemia (aCML)
CML without BCR/ABL fusion gene
– Juvenile myelomonocytic leukemia (JMML)
– MDS/MPD-unclassified
CMML Diagnostic Criteria
MDS/MPD
High vs. low intensity treatment
High intensity = treatment requiring
hospitalization, and included intensive
combination chemotherapy and hematopoietic
cell transplantation.
Low intensity = outpatient-type treatments,
such as use of hematopoietic growth factors,
differentiation-inducing agents, biologic
response modifiers, and low intensity
chemotherapy.
MDS Treatment
Patients < 60 years of age, who have good or excellent performance
status and who are in the IPSS intermediate-2 or high risk categories
(expected survival 0.3 to 1.8 years) = high intensity therapies.
Patients < 60 years of age, who have good or excellent performance
status and who are in the low or intermediate-1 category (expected survival
5 to 12 years) = low intensity therapy or supportive care.
Patients >60 years of age with good performance status and who are in
the IPSS intermediate-2 or high risk categories (expected survival 0.5 to 1.1
years) = low intensity therapy, although selected patients could be
candidates for high intensity therapies.
Patients >60 years of age with good performance status and who are in
the low or intermediate-1 category (expected survival 3 to 5 years) =
supportive care or low intensity therapy
Stem Cell Transplant
HEMATOPOIETIC CELL TRANSPLANTATION
Allogeneic HCT should be considered for patients
with MDS who are under the age of 60 and who
have an HLA-matched sibling donor.