Intro to MDS and MPN

Question 1

Usual presentation of MDS

Answer 1

Older patients (60/70+)
Asymptomatic
In the advanced stage, may see easy bruising/bleeding, fatigue/SOB, fever, infection

Question 2

What are you gonna see on a PBS for MDS?

Answer 2

Hypolobulated neutrophil

RBC macrocytosis

Question 3

How to confirm the diagnosis of MDS?

Answer 3

Bone marrow aspirate/biopsy

Often shows a hypercellular bone marrow and the marrow cells show dysplastic features

Question 4

What is MDS?

Answer 4

Clonal disorder affecting hematopoietic maturation (a type of blood cancer)
Characterized by ineffective hematopoiesis
Bone marrow failure with resultant cytopenias

Question 5

Pathogenesis of MDS

Answer 5

Ineffective hematopoiesis
The marrow is trying to make new cells, but the dysplasia shows that cell development is abnormal
Many cells die before they can leave the marrow
Patients become cytopenic (anemic, thrombocytopenia) even though the marrow is hypercellular

Question 6

Invisible brake

Answer 6

Blood cells arent making it out of the marrow
Ineffective hematopoiesis from hypercellular marrow
In MDS

Question 7

3 risk factors for MDS

Answer 7

Age (more in older)
Exposure to organic compound (like benzene and toluene)
Cigarette smoking

Question 8

Complications of MDS

Answer 8

Fatigue, bleeding and infection due to cytopenia

Progression to AML (worse than just getting AML de novo)

Question 9

3 ways to treat MDS

Answer 9

Supportive and symptomatic (transfuse RBCs and platelets when needed)
Chemo
Allogeneic stem cell transplant (only for young patients)

Question 10

Left shift

Answer 10

Increase numbers of immature cells in the blood
Continuum of developing cells
When the marrow is working very hard

Question 11

Common presentation of MPN

Answer 11

Incidental finding of abnormal blood counts

Symptoms: fatigue, weight loss, night sweats, abdominal fullness (from splenomegaly), anorexia

Question 12

4 types of myeloproliferative disorders

Answer 12

CML
Polycythemia vera
Essential thrombocytosis
Idiopathic myelofibrosis

Question 13

CML pathophys

Answer 13

Malignant clonal disorderof pluripotent stem cells
Increased granulocytic cells (often there is also increased erythroid and platelet lines)
Philadelphia chromosome

Question 14

Philadelphia chromosome

Answer 14

Translocation of chromosomes 9 and 22
Creates a fusion of BCR-ABL gene (oncogene)
Seen in CML

Question 15

3 phases of CML

Answer 15

Chronic phase
Accelerated phase
Blast crisis

Question 16

CML treatment

Answer 16

Tyrosine kinase inhibitor
Specific targeted therapy against BCR-ABL
Improves life expectancy compared to previous therapy
Ex: Imatinib

Question 17

What is polycythemia

Answer 17

Elevated hematocrit
Can have several causes
Spurious: dehydration (increased HCT from low plasma volume)
True: secondary polycythemia can be from hypoxia or high EPO

Question 18

Polycythemia vera pathophys

Answer 18

Excessive RBC production from an abnormal marrow, without EPO stimulation
Mutated JAK2 protein binds to the EPO receptor
Binding promotes signalling independent of EPO stimulation and hypersensitivity to cytokine

Question 19

Clinical presentation of complications of PV

Answer 19

Facial plethora, erythromelalgia
Increased blood viscosity (thrombosis)
Platelet dysfunction (unusual bleeding)
Elevated histamine (itch and PUD)
Increased uric acid (gout)
Progression to myelofibrosis and AML

Question 20

Treatment of PV

Answer 20

Phlebotomy to maintain HCT under 45%

ASA once a day

Question 21

Essential thrombocytopenia

Answer 21

Very high platelet counts
Negative philadelphia chromosome, can be JAK2 positive
Platelets can be functional or dysfunctional (patients can clot or bleed)

Question 22

Treatment for essential thrombocytopenia

Answer 22

Aspirin
Hydroxyura
Ruxotinib (to target the JAK2 mutation)

Question 23

Myelofibrosis

Answer 23

Fibrosis fills the marrow space in idopathic myelofibrosis (IMF)
Patients become cytopenic because there is less hematopoiesis

Question 24

MPN

Answer 24

Excessive unregulated proliferation of myeloid cells