MDS/MPN Flashcards
Mds are characterised by
Dysmyelopoeisis
One or more peripheral cytopenias
Chromosomal anomalies
Variable predilection to undergoing clonal evolution to AML
Dysmyelopoeisis entails….
Is seen in
Hyper or hypocellular bone marrow with impaired morphology and maturation
Seen in mds
Epidemiology of mds
Slight male predominance
More in whites
Median age of onset…7th decade of life
Median age of incidence 65years…ranging from 20->80
Classification of mds
Primary
Secondary
Cellular or morphological
Clinical
Primary mds is also known as?
What is special about it
De novo because it occurs de novo
Special because the cause is unknown and it presents as 60-70% of mds cases
Secondary mds?
Due to exposure to
Tobacco smoke
Herbicides
Chemicals
Ionising radiation
Most importantly alkylating agents and topoisomerase II inhibitors (marrow damaging chemotherapy that accounts for 30% of all mds cases)
Tell me about the pathogenesis of mds?🤔
The major specific pathophysiologic mechanism is ineffective hemopoeisis such that the bm is not producing blood cells effectively and thus cells produced are destroyed in the bm or shortly after they leave the bm
As a result
There is a decreased proportion of cells in the dna synthesis phase of the mitotic cells
And a marked increase in the fraction of late precursor cells undergoing apoptosis
In early stages, increased levels of apoptotic mediators are present in the cells including the tnf alpha fas antigen etc…thus increased apoptosis and proliferation leads to a hypercellular bm with peripheral cytopenias
As the disease progresses and converts into leukemia, a rare gene mutation occurs and a proliferation of leukemia cells overwhelms the healthy marrow leading to progression to AML with decreased apoptosis
Clinical features of mds
P-pallor
L
A- anemia( fatigue,dyspnoea,weakness)
S- splenomegaly or hepatosplenomegaly only in 5-10% of cases
T-thrombocytopenia
I-infection(neutropenia)
C
Lab features of mds
Anemia with high mcv
Tear drop poikilocytosis
Thrombocytopenia with abnormal megakaryocytes
Neutropenia with low NAP score and acquired Pelger huet anomaly of neutrophils
Chromosomal anomalies of mds
Trisomy 8
Loss of long arm of chromosomes 5, 7, 9 20 and 21
Monosomy 7 and 9
Types of mds
Refractory anemia
Refractory anemia with multilineage dysplasia
~ with ringed sideroblasts
~ with excess blasts
Mds- unclassifiable
Mds associated with isolated del(5q) abnormality
AML with multilineage dysplasia
What is refractory anemia
Seen in what condition
Chxd by anemia ,dyserythropeisis and low percentage of blasts in Bm and peripheral blood
What is refractory anemia with ringed sideroblasts
A type of MDS chxd by anemia and the presence of at least 15% ringed sideroblasts(erythroid precursors with iron laden mitochondria forming a perinuclear ring) in the bm
The overlap syndrome definition
Clonal myeloid neoplasms that at the time of initial presentation, have clinical lab or morphological findings that support diagnosis of both mds and mpn
Overlap syndrome include
Cmml
aCML
JMML
MDS/MPN,u
The best characteristic of these latter unclassifiable conditions is refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T)
Cmml?
Chronic myelomonocytic leukemia
A clonal hematopoeitic disease chxd by an increase in monocytes and dysplasia of myeloid precursor cells
Cmml et
<1 case per 100000
Male predominance, median age 72 years
Aetiology is unknown and therapy related
Extremely rare
Lab features of cmml
Mild anemia and Thrombocytopenia with varying white cell count from normal to 80×10⁹/L
Normal being 4.5×10⁹/L
Monocytes may be normal or have AGRANULAR CYTOPLASM WITH ABNORMAL LOBULATED NUCLEIC
Bm is usually hyoercellular and typical dysplasia is found in over 80% of cases
Who diagnosis of cmml
Persistent peripheral blood monocytosis
No philadelphia chromosome or bcr abl fusion gene
No rearrangements of pdgfra and pdgfrb( only excluded in cases with eosinophilia)
Less than 20% blasts in bm and peripheral blood…blasts myeloblasts, monoblasts and promonocytes
Subclassifications of cmml
Cmml 1- blasts<5% in peripheral blood and <10% in the BM
CMML 2- Blasts from 5-19% in the pb and 10-19 in the bm or when Auer rods are present irrespective of blast count
Diagnosis of cmml
Presence of persistent monocytosis
Clonal cytogenetic abnormality or somatic mutation in myeloid cells
It should be noted that the absence of a clonal abnormality makes the diagnosis of cmml uncertain especially in cmml 1 where the monocyte count in both the pb and bm are low
Treatment of cmml
Unsatisfactory
Mainstay-supportive
Drugs hydroxyurea, demethylating agents like azacitidine and decimating when there’s symptomatic organomegaly, infiltrative disease or escalating monocytosis
Imatinib mesylate in rare cases with pdgfrb rearrangements
Median survival-2 years
Please note that in cmml
A rising light often reflects a rising blast count indicating progression to AML in 15-30%of cases.
