MDS/MPN

Question 1

Mds are characterised by

Answer 1

Dysmyelopoeisis
One or more peripheral cytopenias
Chromosomal anomalies
Variable predilection to undergoing clonal evolution to AML

Question 2

Dysmyelopoeisis entails….
Is seen in

Answer 2

Hyper or hypocellular bone marrow with impaired morphology and maturation
Seen in mds

Question 3

Epidemiology of mds

Answer 3

Slight male predominance
More in whites
Median age of onset…7th decade of life
Median age of incidence 65years…ranging from 20->80

Question 4

Classification of mds

Answer 4

Primary
Secondary
Cellular or morphological
Clinical

Question 5

Primary mds is also known as?
What is special about it

Answer 5

De novo because it occurs de novo
Special because the cause is unknown and it presents as 60-70% of mds cases

Question 6

Secondary mds?

Answer 6

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)

Question 7

Tell me about the pathogenesis of mds?🤔

Answer 7

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

Question 8

Clinical features of mds

Answer 8

P-pallor
L
A- anemia( fatigue,dyspnoea,weakness)
S- splenomegaly or hepatosplenomegaly only in 5-10% of cases
T-thrombocytopenia
I-infection(neutropenia)
C

Question 9

Lab features of mds

Answer 9

Anemia with high mcv
Tear drop poikilocytosis
Thrombocytopenia with abnormal megakaryocytes
Neutropenia with low NAP score and acquired Pelger huet anomaly of neutrophils

Question 10

Chromosomal anomalies of mds

Answer 10

Trisomy 8
Loss of long arm of chromosomes 5, 7, 9 20 and 21
Monosomy 7 and 9

Question 11

Types of mds

Answer 11

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

Question 12

What is refractory anemia
Seen in what condition

Answer 12

Chxd by anemia ,dyserythropeisis and low percentage of blasts in Bm and peripheral blood

Question 13

What is refractory anemia with ringed sideroblasts

Answer 13

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

Question 14

The overlap syndrome definition

Answer 14

Clonal myeloid neoplasms that at the time of initial presentation, have clinical lab or morphological findings that support diagnosis of both mds and mpn

Question 15

Overlap syndrome include

Answer 15

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)

Question 16

Cmml?

Answer 16

Chronic myelomonocytic leukemia
A clonal hematopoeitic disease chxd by an increase in monocytes and dysplasia of myeloid precursor cells

Question 17

Cmml et

Answer 17

<1 case per 100000
Male predominance, median age 72 years
Aetiology is unknown and therapy related
Extremely rare

Question 18

Lab features of cmml

Answer 18

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

Question 19

Who diagnosis of cmml

Answer 19

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

Question 20

Subclassifications of cmml

Answer 20

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

Question 21

Diagnosis of cmml

Answer 21

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

Question 22

Treatment of cmml

Answer 22

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

Question 23

Please note that in cmml

Answer 23

A rising light often reflects a rising blast count indicating progression to AML in 15-30%of cases.