Myeloproliferative Disorders

Question 1

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

Answer 1

• Ineffective hematopoesis

- Inc risk of transformation to acute leukemia

Question 2

List the 2 clinical scenarios of MDS.

Answer 2

• Idiopathic (50% cyto. abnormal), old age

- Secondary MDS (Think Therapy AML after alk/rad): 2-8yrs post-treat., -5 or -7 karyotype

Question 3

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

Answer 3

• CBC w/ diff
• BM biopsy, look for dysplasia
• Inc myeloblasts in blood or marrow, but <20%
• Karyotype or FISH for cytogenetic abnormality
• Flow cytometry for blast increase & abnormal phenotype (expressing wrong surface marker)

Question 4

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

Answer 4

• Vitamin def (B12, folate, etc)
• Toxin exposure (e.g. heavy metals)
• 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: <2% blood

• RCUD: 1 lineage, GOOD prognosis
• RCMD: 2+ lineages, WORSE prognosis

High grade: 5-19% marrow, 3-19% blood
- RAEB1: 5-9%,2-4%
- RAEB2: 10-19%, 5-19%
Both dismal prognosis, RAEB2 is slightly worse

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

Similar: clonal hematopoetic neoplasm from progenitor, replaces normal cells. Takes over marrow. Overtakes in multiple lineages since it was multi potent. However, it is capable of giving rise to normal blood cells (often makes too many)

Question 7

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

Answer 7

• Sequestration of excess blood cells in vascular sinuses of liver & spleen
• Extramedullary hematopoiesis because marrow is fibrotic

Question 8

List 3 possible negative end points for MPNs

Answer 8

• Transformation to AML (but sometimes ALL). In the setting of a prior MPN, transformation to acute leukemia is often referred to as blast phase
• Development of myelodysplasia with ineffective hematopoiesis (transform to MDS)
• 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)

• 9;22 BCR-ABL fusion (p210 NOT 190-ALL)
• Neutrophilia (100k, 11k is norm), basophilia
• BM: Markedly hypercellular; Granulocytic hyperplasia; Small megakaryocytes with round, non-lobated nuclei.

Polycythemia vera (PV)

• JAK2 mutation (V617F pt mut.)
• Erythrocytosis (usually inc nets & plats too)
• BM: trilineage hyperplasia; clusters of large, bizarre megakaryocytes.

Primary myelofibrosis (PMF)

• 50% are JAK2 mutations
• Inc granulocytes & megakaryocytes, progression to myelofibrosis. LACKS ERYTHROCYTOSIS
• BM: Hypercellular w/ gran & mega, then fibrotic

Essential thrombocythemia (ET)

• 50% are JAK2 mutations
• Thrombocytosis only; (no inc RBC or granulo)
• BM: marrow is normocellular. No granulocyte hyperplasia; clustered, atypical megakaryocytes

Question 10

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

Answer 10

Some CML pts developed resistance to imatinib via mutations in the imatinib binding site of the fusion protein

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

Venous or arterial thrombosis –> DVT, MI, stroke

Consider PV when thrombosis occurs at mesenteric vein, portal vein, or splenic vein

Question 12

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

Answer 12

Phlebotomy & aspirin

Question 13

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

Answer 13

Left shift of R & W BCs. Increased # of…

• immature granulocytes (myelocytes, metamyelocytes)
• immature RBCs (nucleated)
• Tear drop RBCs (dacrocytes).

Question 14

Explain the basis for the findings in #13 in patients with marrow fibrosis.

Answer 14

Basically, marrow is so fibrotic that immature cells are forced out early, and RBCs are literally being squeezed out (hence shape)