Chronic Myeloproliferative Disorders

Question 1

List the 4 major myeloproliferative disorders

Answer 1

Chronic myelogenous leukemia (CML)
Polycythemia vera
Essential thrombocytosis
Primary myelofibrosis

Question 2

Chronic Myelogenous Leukemia (CML)

Describe the bone marrow cellularity and hematopoiesis

Answer 2

Bone marrow cellularity and hematopoiesis are both increased

Question 3

What is a classic symptom of all myeloproliferative disorders?

Answer 3

Splenomegaly

Question 4

Chronic Myelogenous Leukemia (CML)

What genetic abnormality is present?

Answer 4

t(9;22)

BCR-ABL fusion gene (Philadelphia chr)

Question 5

What is the common pathogenic feature in all myeloproliferative disorders?

Answer 5

Mutated, constitutively activated tyrosine kinases

Question 6

Chronic Myelogenous Leukemia (CML)

Describe what you would find on analysis of peripheral blood

Answer 6

High WBC count
Shift to immaturity (earlier stages like band PMNs, myocytes present)
High basophil counts

Question 7

Chronic Myelogenous Leukemia (CML)

Describe the cellularity of the bone marrow

Answer 7

Cellularity is 100% (no fat cells seen in bone marrow) regardless of age

Question 8

What usually causes a leukemoid reaction?

Answer 8

Infection

Question 9

CML vs Leukemoid Reaction

WBC Count

Answer 9

CML is over 50,000/uL

Leukemoid is usually under 50,000/uL

Question 10

CML vs Leukemoid Reaction

Are the cells mature or immature?

Answer 10

CML - see all stages of maturation present

Leukemoid - Almost all mature

Question 11

CML vs Leukemoid Reaction

What clinical finding might you feel in both (but more commonly in CML)?

Answer 11

Splenomegaly

Question 12

Chronic Myelogenous Leukemia (CML)

Describe the onset and progression of CML

Answer 12

Onset is gradual and progresses slowly

50% of patients enter an accelerated phase with decreased response to treatment, anemia, thrombocytopenia, and may transform to a “blast phase” (an acute leukemia)

Question 13

Chronic Myelogenous Leukemia (CML)

Treatment

Answer 13

Allogeneic bone marrow transplant
IFN-alpha (disliked due to adverse effects)

Imatinib (Gleevac)
Preferred treatment
ABL-specific tyrosine kinase inhibitor
Will normalize WBC counts, improve survival and quality of life

Question 14

Polycythemia Vera

How can it be “relative” or “absolute”?

Answer 14

Relative - decrease in plasma volume lead to an artificial increase in Hct

Absolute - absolute increase in total RBC mass

Question 15

Polycythemia Vera

What mutation commonly causes it?

Answer 15

JAK2 mutation

Question 16

Polycythemia Vera

Pathophysiology

Answer 16

Progenitor cells have a decreased need for EPO (EPO levels are low in the blood)

Question 17

Polycythemia Vera

Clinical and Lab Features

Answer 17

Insidious onset usually in late middle age

RBC counts elevated
Hematocrit may be 60% or higher (normal ~35-50%)

Bone marrow is hypercellular with proliferation of erythroid forms (and granulocytes and megakaryocytes)

Question 18

Polycythemia Vera

Complications

Answer 18

Abnormal blood flow (stasis and vascular distension)
Thrombosis
Bleeding
HTN
Patient may become plethoric (red complexion)

Question 19

Polycythemia Vera

Treatment

Answer 19

Therapeutic phlebotomies (collecting blood and discarding it to lower Hct)

Question 20

Primary Myelofibrosis

What mutations may be present?

Answer 20

JAK2
CALR
MPL

Question 21

Primary Myelofibrosis

What is the primary problem?

Answer 21

Excess collagen deposition (fibrosis) in the bone marrow

Question 22

Primary Myelofibrosis

Describe the progression of the disease

Answer 22

Early phase has hypercellular marrow and not much fibrosis.

Late phase has thick, sclerotic, fibrotic marrow

Question 23

Primary Myelofibrosis

Describe the leukoerythroblastic blood picture

Answer 23

Nucleated RBCs

Tear drop RBCs

Question 24

Primary Myelofibrosis

What stain may be done on the bone marrow to better visualize the fibrosis?

Answer 24

Reticulin stain (type III collagen)

Question 25

Essential Thrombocytosis

What is the primary problem and its major complications?

Answer 25

High platelet counts

Thrombosis or hemorrhage are the main complications

Question 26

Essential Thrombocytosis

Treatment

Answer 26

Aspirin (to prevent thrombosis)