Hemonc Test 1 (11): Myeloproliferative And Myelodysplastic Syndromes

Front 1

What is erythrocytosis?

Back 1

An increase in the number of circulating RBCs per volume of blood
= polycythemia
Reflected as an elevated hemoglobin and hematocrit

Front 2

What are the three major categories of erythrocytosis?

Back 2

Relative erythrocytosis - normal red cell mass but decreased plasma volume
Secondary erythrocytosis - due to elevated erythropoietin level
Primary erythrocytosis - a.k.a. polycythemia vera

Front 3

What is the predominant cause of secondary erythrocytosis?

Back 3

Chronic tissue hypoxia, which causes increased erythropoietin production by the kidney
Less common causes include: tumors of the liver or kidney which secrete erythropoietin; rare genetic disorders; treatment with erythropoietin or androgens

Front 4

What is Hyperviscosity Syndrome -- symptoms

Back 4

Symptoms: headaches, visual changes, tinnitus, dizziness, paresthesias, decreased mental acuity,

Front 5

What are other causes of tissue hypoxia which leads to erythrocytosis?

Back 5

*obstructive sleep apnea, high carboxyhemoglobin levels*

life at high altitude, high affinity hemoglobins, cardiopulmonary disease, obesity-hypoventilation syndrome

Front 6

Define Myeloproliferative disorders

Back 6

Stem Cell Disorders
lead to autonomous production of hematopoietic cells from all three lineages (red, white, platelets)
All these disorders are clonal

Front 7

What is Polycythemia Vera?

Back 7

A neoplastic disorder arising from a pluripotent stem cell, generally characterized by erythrocytosis, with or without concomitant thrombocytosis and leukocytosis

Front 8

Where are the cells derived in P. vera?

Back 8

Many if not all of the circulating blood cells are derived from a single neoplastic stem cell (rather than a multitude of hematopoietic stem cells like normal)

Front 9

What do normal erythroid progenitor cells require for proliferation that cells in patients with P. vera do NOT require?

Back 9

Erythropoietin

Front 10

How is P. vera diagnosed?

Back 10

Low or undetectable erythropoietin level
positive JAK2 mutation test

Front 11

What is the natural history of P. vera?

Back 11

Latent, asymptomatic phase
Proliferative phase
Spent phase
Secondary AML

Front 12

What symptoms are associated with the proliferative phase of P. vera?

Back 12

patient may be hypermetabolic
symptoms of hyperviscosity or thrombosis

Front 13

What symptoms/findings are associated with the spent phase of P. vera?

Back 13

anemia, leukopenia, secondary myelofibrosis, increasing liver and spleen size

Front 14

What findings and treatments are associated with secondary AML (progression of P. vera)?

Back 14

1-2% of patients treated with phlebotomy alone
Certain drug therapies increase risk

Front 15

What are the symptoms associated with P. vera?

Back 15

Those common to all erythrocytosis: headache, decreased mental acuity, weakness
More specific to P. vera: pruritis after bathing, erythromelalgia- red palms/soles, hypermetabolic symptoms, thrombosis, hemorrhage

Front 16

What physical exam findings are associated with P. vera?

Back 16

facial plethora (fullness), splenomegaly, hepatomegaly, distension of retinal veins

Front 17

What lab findings are associated with P. vera?

Back 17

*low epo levels and positive JAK2 V617F*
increased Hgb, Hct, WBC, platelets
basophilia
increased uric acid and B12

Front 18

How do you treat P. vera?

Back 18

Phlebotomy (reduce risk of cardiac & thrombotic events)
Hydroxyurea (myelosuppressive agent)
Low dose aspirin (reduce risk of thrombosis)

Front 19

What are the risks of phlebotomy as treatment for P. vera?

Back 19

Increased risk of thrombosis
No effect on progression to spent phase

Front 20

Essential Thrombocytosis

Back 20

Incidence similar to P. vera
20% of patients are <40 years old
Exact pathophysiology is unclear

Front 21

How is Essential Thrombocytosis (ET) diagnosed?

Back 21

First, rule out secondary causes of thrombocytosis (cancer, infection, inflamm, bleeding, iron deficiency)
Platelet count should be >600 on 2 separate occasions, at least 1 month apart
Exclude CML by absence of Philadelphia chromosome

Front 22

What is the natural history of ET?

Back 22

May progress to myelofibrosis
Major complication is thrombosis (20-30% of patients; arterial or venous)

Rarely progresses to AML

Front 23

What symptoms are associated with ET?

Back 23

Many patients are asymptomatic at time of diagnosis
Digital ischemia from microvascular thrombi
Erythromelalgia
Pruritis
Hemorrhage

Front 24

What lab findings are associated with ET?

Back 24

If the platelet count is very high, there may be *pseudohyperkalemia and pseudohypoglycemia*
Iron studies and sedimentation rate should be normal
Platelets can be very large and bizarrely shaped; marrow shows clusters of abnormal megakaryocytes

Front 25

How do you treat ET?

Back 25

Reduce the platelet count
Treat those who have had or are at risk for thrombosis, those >60 y.o.
Hydroxyurea

Front 26

What is myelofibrosis (MF)?

Back 26

Clonal stem cell disorder affecting megakaryocytes predominantly

Front 27

What makes it difficult to distinguish the "spent phase" of all myeloproliferative disorders from primary MF?

Back 27

All myeloproliferative disorders can result in a fibrotic "spent phase" which can be difficult to distinguish from primary MF

Front 28

What are the symptoms and natural history of MF?

Back 28

Median survival is 5 years
transforms into AML in 5-20%
Symptoms: >50% patients present with sx of anemia and thrombocytopenia; maybe fever, sweats, weight loss; maybe abd pain, early satiety as spleen enlarges

Front 29

What physical exam findings are associated with MF?

Back 29

Massive splenomegaly; hepatomegaly

Front 30

What lab findings are associated with MF?

Back 30

Early on: increased PLTs and normal Hgb & WBC
As disease progresses: anemia, decreased PLTs & WBC
*Peripheral smear: leukoerythroblastic picture with teardrops, NRBC and early granulocytes
"Dry tap" (no liquid aspirate from marrow, increased collagen)

Front 31

How do you treat MF?

Back 31

No definitive therapy, except supportive measures
BM transplant in younger patients (under 65y.o)
Splenectomy if patient has abdominal pain
Ruxolitinib (JAK-2 inhibitor) to treat hypermetabolic symptoms, splenomegaly; does not improve blood counts

Front 32

What are myelodysplastic syndromes (MDS)?

Back 32

Conditions in which there is disordered maturation in 1 or more cell lines, usually producing cytopenias

Front 33

What is the progression of MDS's?

Back 33

The abnormal clone of cells can remain stable or progress, generating further clones with worsening cytopenias and further cytogenetic abnormalities
*at the end of progressive worsening --> AML, with decreased chance of remission*

Front 34

What are the clinical features of MDS? Who is affected by MDS? Findings/Symptoms?

Back 34

This is a disease of the elderly (older than 60)
Abnormal (low) CBC
Symptoms of anemia, thrombocytopenia

Front 35

What lab findings are associated with MDS?

Back 35

Any cell line or combination of cell lines can be affected
Peripheral cell abnormalities:
-- macrocytosis of RBC
-- neutrophils: hypogranular or bilobed
-- can have large PLTs &/or monocytosis

Front 36

What marrow findings/features are associated with MDS?

Back 36

Megaloblastic erythropoeisis
Ringed sideroblasts
Dyserythropoiesis (abnormal or multiple nuclei of RBC precursor)
Small megakaryocytes with hypolobate nuclei
*Blast cells <20% of marrow cells

Front 37

What cytogenetic abnormalities are associated with MDS?

Back 37

Monosomy 5,7,8
Deletion of the long arm of 5 (5q-) is associated with a better prognosis
Multiplicity of cytogenetic abnormalities is associated with poor prognosis

Front 38

How do you treat MDS?

Back 38

Usually supportive
Transfusions (RBC and platelets) as necessary
Growth factors (epo and G-CSF)
Thalidomide
Certain agents that cause DNA hypomethylation