Meloproliferative Disorders

Question 1

All myeolproliferative disorders can progress to ….

Answer 1

May progress/transform to Acute Myeloid Leukemia (AML)

Question 2

Define: Arises from the neoplastic transformation of a single hematopoietic multipotential cell

Answer 2

Myelofibrosis

May be Primary or Secondary

Secondary MF occurs following other myeloproliferative disorders

May evolve from Essential Thrombocytosis (or others)
2/2 atypical megakaryocytes

Question 3

Pathogenesis of Myelofibrosis

Answer 3

Fibrous tissue develops intrameduallary

So extra medially hematopoiesis
(Spleen, liver) kick in
Leads to Hepatomegaly/ Splenomegaly

Question 4

What is the smoking gun for Myelofibrosis on peripheral blood smear

Answer 4

Dacrocytes

Poikilocytosis
(Qualitative platelet disorder)

Question 5

What is the treatment approach to Myelofibrosis

Answer 5

Observe and Supportive Care

-Anemia: transfusions as necessary
Immunosuppressants

-splenomegaly: 1st line hydroxyurea
Is no response: splenectomy
(Advanced dz)

Question 6

What is Ruxolitinib

Answer 6

an oral JAK2 inhibitor, is approved by the FDA for use in patients with intermediate- or high-risk myelofibrosis

Question 7

Who do we send myelofibrosis pts to

Answer 7

Hematology

Question 8

chart on slide 18 from lecture 2, myeloproliferative disease, draw on white board

Question 9

Define: 
-Acquired myeloproliferative disorder
-overproduction of all three hematopoietic cell lines
-most prominently red blood cells
Results in hyperviscosity of the blood

Answer 9

Polycythemia Vera

-Mutation in exon 12 or 14 of JAK2 !!(V617F)

Question 10

A pt presents with generalized pruritus following a warm shower or bath

Think

Answer 10

Polycythemia Vera

related to histamine release from basophilia

Assoc s/s

• Headache, dizziness, tinnitus, blurred vision, epistaxis
• complaints related to expanded blood volume and increased blood viscosity

Question 11

What is erythomelalgia

Answer 11

(painful burning of the hands accompanied by erythema)

assoc. with polythemia Vera

Question 12

Hallmark lab finding in Polycythemia Vera

Answer 12

Elevated H/H at sea level

With a normal cell morphology

Question 13

What is the Dx for Polycythemia Vera

Answer 13

Diagnosis should be confirmed with JAK2 mutation screening

Positive in 95%-98% of patients
-The absence of a mutation in either exon 14 or exon 12 should lead the clinician to question the diagnosis

Question 14

What is the mainstay of treatment for polycythemia Vera

Answer 14

Phlebotomy!!

+ low dose aspirin
+allopurinol for hyperuricemia
+antihistamines to manage pruritus

AVOID Alkylating Agents
(Can lead to acute leukemia)

Resistant: JAK2 Inhibitor (Ruxolitinib)

Question 15

Referral for Polycythemia Vera

Answer 15

Refer all cases of polycythemia vera to hematology

Question 16

Finding an incidental high platelet count on CBC

Think

Answer 16

Essential Thrombocytosis

Treat with oral hydroxyurea

Question 17

Answer 17

Erythromelalgia

Seen in Essential Thrombocytosis and Polycythemia Vera

Question 18

Answer 18

Live do reticularis

Seen in essential Thrombocytosis

Question 19

Hallmark lab finding in essential Thrombocytosis

Answer 19

Isolated elevated Platlets (>2 mil.)

Question 20

Treatment for Essential Thrombocytosis

Answer 20

Hydroxyurea

• Dosage titrated to keep platelet count < 500,000 µL
• Anagrelide (when hydroxyurea not well tolerated because of anemia)

Aspirin
81mg/day orally (rule out acquired von Willebrand syndrome first)
Erythromelalgia responds rapidly to aspirin

Strict control of coexistent cardiovascular risk factors is mandatory for all patients

Question 21

Refer all cases of essential Thrombocytosis to…

Answer 21

hematology

Question 22

If you see Philadelphia chromosome 22.. .think ..

Answer 22

Chronic Myelogenous Leukemia!
(CML)

Detected with PCR

Question 23

What are the three phases of CML

Answer 23

-Chronic Phase
Does not behave like a malignant disease
Normal bone marrow function is retained
80-90% of patients present in this phase

-Accelerated Phase
Progressive anemia and thrombocytopenia
Increasing % of blasts in blood and bone marrow

-Blast Crisis
≥ 20 percent blasts in peripheral blood or bone marrow
Resembles acute leukemia

Question 24

A pt presents w/ fatigue, night sweats, low grade fever, and abdominal fullness (splenomegaly), cachexia, and STERNAL tenderness..
think

Answer 24

Chronic Myelogenous Leukemia

-Sternal tenderness
marrow overexpansion
Particularly in the lower portion of the sternum

Question 25

Finding elevated WBC with basophillia

Think

Answer 25

Basophillia is weird

So think Chronic Myelogenous Leukemia

Question 26

What is the treatment for Chronic Myelogenous Leukemia

Answer 26

Chronic Phase
Goal: Normalization of hematologic abnormalities and suppression of the malignant bcr/abl - expressing clone
-Tyrosine kinase inhibitor (targets the abl kinase)
1st gen: Imatinib
2nd gen: Nilotinib and Desatinib

Question 27

Tyrosine Kinase Inhibitors

Answer 27

First generation
-Imatinib – 98% control of chronic phase disease

Second generation
-Nilotinib and dasatinib – used to salvage patients not responding to imatinib

Normalization of blood counts and splenomegaly in 3 months

Cytogenic response in 3-6 months

Major molecular response in 12 months

Question 28

What is the treatment to leukostasis in chronic Myelogenous leukemia

Answer 28

Emergent leukapheresis and myelosuppression

-Hydroxyurea

Question 29

Refer all cases of CML to…

Answer 29

Hematology