Myeloproliferative Disorders

Question 1

Basic principles of MPD

Answer 1

Neoplastic proliferation of mature cells of myeloid lineage. This results in a high WBC count with hyper cellular BM because the cells of all myeloid lineages are increased. Complications include increased risk for hyperuricemia and gout due to high turnover of cells. Additionally, progression to marrow fibrosis or transformation to acute leukemia.

Question 2

Cell type and mutation associated with CML

Answer 2

Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors. Basophils are characteristically increased. Driven by t(9;22) which generates BCR-ABL fusion protein with increased tyrosine kinase activity (a signal transducer, therefore leading to overgrowth).

Question 3

First line tx for CML

Answer 3

Imatinib – blocks tyrosine kinase activity.

Question 4

How to distinguish between CML and a leukemia reaction (reactive neutrophilic leukocytosis)

Answer 4

Negative leukocyte alk phos stain and increased basophils. Additionally, t(9;22) is absent in leukemia reaction. LAP score however MAY be increased in the presence of subsequent secondary infections so for this reason, the presence of philadelphia chromosome should be determined in suspicious cases.

Question 5

Clinical sx of polycythemia vera

Answer 5

Sx due to hyperviscosity – increased risk of venous thrombosis, flushed face due to congestion. Itching especially after bathing due to histamine release from increased mast cells. Bleeding due to impaired platelet function.

Question 6

Diagnostic labs in polycythemia vera

Answer 6

Elevated RBC count, Hgb, and hct >50. Thrombocytosis and leukocytosis may be present. Serum EPO is reduced because high Hgb, hct, oxygen, and/or RBC all suppress the release of Epo. Elevated vitamin B12. JAK2 V617F present in >95% of PV pts. BM biopsy confirms dx.

Question 7

Tx of polycythemia vera

Answer 7

First line: phlebotomy Second line: hydroxyurea