Onc.2 Myeloproliferative Disorders

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approach to increased cell count:

primary vs secondary (4 points)

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def'n of myeloproliferative neoplasm?

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= too many mature myeloid cells

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note: myelofibrosis leads to extramedullary production in spleen, liver, LN's...

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d

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myeloproliferative neoplasms (MPN)

pathophys? 3

and risk of transformation to...

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note: different ways to classify MPN...

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current disease classification based on molecular understanding of disease.. but clinical features stlil important

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significance of

1. BCR ABL mutation

2. JAK 2 mutation

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note MPN's that fall into each of the following categories

1. BCR-ABL negative vs. BCR-ABL positive

2. JAK2 pos vs. JAK2 indeterminate

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term glossary..

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•60 yo man from the Middle East. Works as amechanic. He has hypertension and TypeII diabetes. His BMI is >30. He has a 40 pack year smoking history. He has been having intermittentheadaches. Tells me that his brothersometimes has blood “taken off” for this. He has a CBCd done.

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CBC shows isolated polycythemia

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DDx of polycythemia

5 secondary

1 primary

NB

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NB: investigations and workup of polycythemia

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NB: signs and Sx of PV 6

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1. head: fullness, headaches, conjunctival injection

2. splenomegaly: early satiety

3. Erythromelalgia: burning, painful extrem

4. Joints: gout

5. Skin: pruritis that is worse after shower

6. Thrombosis (cardiac events, stroke, DVT, PE, unusual clots (mesenteric and CNS)

note that weird clots are a red flag..

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Investigations of suspected primary PV:

History

Physical

CBC (2)

Chemistry

Blood Film

Special tests

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notes: dyspepsia from too much histamine --> hyperacidic

microcytic as they tend to run out of building blocks in PV..

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3 special tests in PV and the utility

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note: would expect EPO to be high if exogenous or ectopic production..

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back to first case... what is his Dx and management

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Example CBC of patient with JAK2 positive PV

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summary of polycythemia vera

1. definition

2. incidence

3. demographic

4. prognosis

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diagnostic criteria for PV

2 major

3 minor

need 2 major and 1 minor OR first major and 2 minor

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list complications of PV 4

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PV therapy 3 routine, 3 high risk/specific

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DDx of thrombocytosis (4 secondary, vs. primary causes 5)

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workup of thrombocytosis

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Suspected Primary Thrombocytosis:

History

Physical

CBCd

Chemistry

Blood film

Special Tests

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Thrombocytosis with giant platelets (arrow)

Numerous platelets are noted in thepeipheralblood smear from a patient with CML. Giant platelets (arrow) are alsoappreciated.This is a giant platelet.. Andprobably too many pltfor this smear.

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Essential thrombocytopenia

1. definition

2. incidence

3. demographics

4. prognosis

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Diagnostic criteria for essential thrombocytosis

note diagnoses to exclude...

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Complications of ET

1. bleeding?

2. thrombosis

3. risk of progression to...

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Tx of ET

1. tx to reduce thrombotic event..

2. when to use cytoreductive therapy?

3. other tx?

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DDx of neutrophilia? 6

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Primary MPD vs. 2ndary MPD

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possible clues to a primary MPD

CBC findings (2)

Blood film

Exam finding?

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Note: which MPDs have elevated neutrophil counts?

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all of them. PV, ET, MF, CML

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which MPD's have increased myeloads

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•Myeloidscan be seen in other MPD, but classically CML has the whole spectrum of myeloidprecursors (blasts, promyelocytes, myelocytes, metamyelocytes, bands, neuts)

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Early presentation of CML? CBC findings?

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•Early presentation of CML may not have asignificant component of myeloid precursors

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NB: if BCR ABL negative, which MPD is excluded

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CML

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Peripheral blood smear shows granulocytosis withall stages of maturation.

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CML:

1. def'n

2. mutation

3. CBC findings

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CML: incidence, median age, prognosis

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Philadelphia chromosome and the BCR ABL oncogene

1. def'n

2. result of the BCR ABL fusion protein

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Natural History of CML

1. chronic phase (duration)

2. accelerated phase (duration)

3. Blast crisis (median survival)

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CML:

% diagnosed in each stage?

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40% on routine lab tests and are asymptomatic

85-90% diagnosed in chronic phase

10-15% accelerated or blast phase

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typical Sx of CML

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overall "hypermetabolic"

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Unusual presentations of CML...

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–Leukostasis: sluggish blood flow associatedwith very high wbc counts (>250)•

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CML: what is the treatment

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targeted therapy. very effective.

Imatinib/Gleevac is a tyrosine kinase inhibitor.

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CML: treatment

1. how is response to therapy measured?

2. tracking the response?

3. do they ever stop the drug?

4. % of patients taht fail treatment?

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case 4

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Case 4: blood film report

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this person needs a hematology consult

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Important findings in primary myelofibrosis (PMF)

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1. splenomegaly

2. Leucoerythroblastic blood film

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DDx of splenomegaly (4 big categories)

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hematologic causes of splenomegaly (SM)

1. malignant (3)

2. non malignant (2)

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congestive causes of SM 3

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cirrhosis,

splanchnic thrombosis

CHF

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Infectious causes of SM 3

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1. viral

2. parasite

3. Infective endocarditis

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Infiltrative cause of SM 4

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1. sarcoid

2. RA/SLE

3. Gaucher's

4. metabolic storage disorders

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1. def'n of a leucoerythroblastic blood film

2. DDx 4

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workup of case 4 ..

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marrow fibrosis in primary myelofibrosis (reticulin stain)

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primary myelofibrosis

def'n

features

phases (2)

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features: fibrosis, SM

phases: proliferative and fibrotic

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Diagnostic criteria for PMF

1. marrow features

2. genetic/molecular/CBC findings

3. diagnoses to exclude

4. other supporting features 4

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Myelofibrosis

1. typical age?

2. prevalence

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1. older patient (60s-70s)

2. Least common of the MPD

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early and late presentation of MPD

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complications of Myelofibrosis (8)

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Prognosis Myelofibrosis?

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variable

median survival is 5 years for patients who are anemic

patients with normal cell counts have median survival up to 15 y

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Tx of Myelofibrosis

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