Myeloproliferative disorders

Question 1

List the 2 main features that characterize myelodysplastic syndrome (MDS).

Answer 1

1) Ineffective hematopoiesis: cannot make normal functioning blood cells, often die before leaving marrow. Look abnormal (dysplastic)
2) Increased risk of transformation to acute leukemia (AML)

Question 2

List the 2 clinical scenarios of MDS.

Answer 2

Primary (idiopathic) MDS

Secondary MDS (usually therapy-related MDS)

Question 3

List 3 different types of tests that could be performed to make a diagnosis of MDS.

Answer 3

1) morphological evidence of dysplasia
2) Increased myeloblasts, but less than 20% of blood and marrow cells
3) presence of a clonal cytogenic abnormality

Question 4

List 4 possible causes of secondary myelodysplasia that might mimic MDS.

Answer 4

• Vitamin deficiency (B12, folate, etc)
• Toxin exposure (eg. heavy metals)
• Exposure to certain drugs
• Viral infections

Question 5

Contrast low grade MDS and high grade MDS with regards to diagnostic criteria and prognosis.

Answer 5

Low grade MDS: myeloblasts account for <2% of blood cells, Better progrnosis than high grade MDS, especially with unilineage dysplasia

High grade MDS: Myeloblasts account for 5-19% of marrow cells, and/or 3-19% of blood cells. Very poor prognosis

Question 6

Compare and contrast MDS and myeloproliferative neoplasms (MPNs) in regards to usual number and appearance/functionality of cells in the blood and marrow.

Answer 6

MPNs give rise to increased numbers of normal blood cells of one or more lineages. Much less likely to transform into acute leukemia than MDS.

Question 7

List 2 reasons for the frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs.

Answer 7

1) Sequestration of excess blood cells

2) Extramedullary hematopoiesis

Question 8

List 3 possible negative end points for MPNs.

Answer 8

1) Transformation to acute leukemia (referred to as blast phase)
2) Development of myelodysplasia with ineffective hematopoeisis
3) Excessive marrow fibrosis with resultant bone marrow failure

Question 9

Compare and contrast the 4 MPNs covered in the notes with regard to blood cell counts, marrow findings, and usual cytogenetic and molecular abnormalities.

Answer 9

Chronic Myelogenous Leukemia (CML):

• Leukocytosis primarily due to neutrophilia, basophils are also usually increased. WBC 12K-100K
• Hypercellular marrow due to granulocytic hyperplasia.
• BRC-ABL1 gene fusion, usually from t(9;22)(q34;q11.2), with the resultant fusion gene being located on the derivative chromosome 22, aka Philadelphia Chromosome.

Polycythemia Vera (CV)

• Chiefly an increase RBC (erythrocytosis), also increased neutrophils and platelets.
• Trilineage hyperplasia in the marrow, clusters of bizarre megakaryocytes
• Activating mutation of JAK2, usually a V617F point mutation.

Primary Myelofibrosis (PMF):

• Granulocytic hyperplasia, megakaryocytic hyperplasia, no erythrocytosis
• Significant reticulin fibrosis of the marrow during fibrotic stage
• JAK2 mutations are present in around 50% oc PMF cases

Essential Thrombocythemia (ET):

• Persistent thrombocytosis
• JAK2 mutations are present in around 50% of cases

Question 10

Explain why there is a need for a second and third generation of protein tyrosine kinase inhibitors (PTKIs)

Answer 10

Some CML patients develop resistance to imatinib through mutations altering the imatinib binding site of the fusion protein, resulting in the need from 2nd and 3rd gen. PTKIs.

Question 11

Recall the most common method of death attributable to disease in polycythemia vera (PV) patients, and list 3 sites where thrombosis should always make one consider the possibility of PV.

Answer 11

Thrombotic events are the most common cause of death attributable to disease in PV patients.

Thrombosis of the mesenteric vein, portal vein, or splenic vein SHOULD ALWAYS RAISE THE POSSIBILITY OF PV.

Question 12

Recall the (somewhat archaic) most common treatment for PV.

Answer 12

Phlebotomy and aspiring therapy.

Occasionally mild chemotherapy is used.

Question 13

List findings that might be seen in the peripheral blood smear in a patient with leukoerythroblastosis.

Answer 13

Immitature granulocytes and immature red cells.

Question 14

Explain the basis for the findings in #8 in patients with marrow fibrosis.

Answer 14

Bone marrow with significant reticulin fibrosis, with loss of much of the marrow space. This may result in hematopoiesis being present within the marrow sinusoids.