CML and myeloproliferative disorders

Question 1

what is a myeloproliferative disorder

Answer 1

clonal prolif of 1 or more haematopoietic components (inc production of mature cells)

classified based on dominant cell line involved

Question 2

what translocation is associated with the philidelphia chromosome

Answer 2

9,22

Question 3

what myeloproliferative disorders are philidelphia Chr pos and neg

Answer 3

\+ve = CML 
-ve = polycythemia vera, essential thrombosis, myelofibrosis

Question 4

what is the significance of the JAK2 mutation

Answer 4

asso with philidelphia Chr -ve MPDs

asso with 95% of PolyVera cases

Question 5

findings in polycythemia

Answer 5

inc RBC mass, inc Hb, inc packed cell vol

Question 6

causes of polycythemia

Answer 6

primary = PolyVera, familial poly
secondary (due to inc EPO) = inc altitude, chronic hypoxia (COPD), drugs
Pseudo = dec plasma vol, dehydration, D&V, burns

Question 7

how will polycythemia ruba vera present

Answer 7

hyperviscosity, hypervol, hypermetabolism
-> blurred vision, headache, red nose, gout, thrombosis/stroke, splenomeg
Itchy after contact with water

Question 8

what mutation is associated with polycythemia RV

Answer 8

JAK2 V617F point mut

Question 9

investigative findings in polycythemia RV

Answer 9

inc HB, inc Hct, dec circulating EPO

BM dominated by erythoid precursors

Question 10

treatment and maintenance of polycythemia ruba Vera

Answer 10

Tx = venesection
maintenance = hydroxycarbamide, aspirin

Question 11

what are the clinical features of essential thrombosis

Answer 11

often incidental findings

venous/arterial thrombosis, gangrene, haemorrhage, headache, dizziness, visual disturbances

Question 12

what are the investigative findings in essential thrombosis

Answer 12

platelets sustained >600
megakaryocytes dominate BM
blood film - large platelets and megakaryocyte fragments

Nb 50% associated with JAK2

Question 13

treatment for essential thrombosis

Answer 13

aspirin
anagrelide (dec plt formation)
hydroxycarbamide

Question 14

pathology of myelofibrosis

Answer 14

MPD mainly of megakaryocytes and granulocytic cells

-> reactive BM fibrosis with extramedullary haematopoiesis

Question 15

causes of myelofibrosis

Answer 15

primary - 50% = JAK2

secondary - leukemia, hypoparathyroidism, drugs

Question 16

Clinical features of myelofibrosis

Answer 16

extramedullary haematopoiesis -> hepatomeg + massive splenomeg, weight loss, fever

often presents in elderly, may be with Budd-Chiari syndrome (abdo pain, ascites, hepatomeg)

Question 17

investigative findings in myelofibrosis

Answer 17

film = tear drop poikilocytes, leukoerythroblasts
Bm = dry tap (due to fibrosis)

Question 18

treatment for myelofibrosis

Answer 18

supportive
SCT
Ruxolitinib = JAK2 inhib
hydroxycarbamide, thialidamide, steroids

Question 19

how will CML present

Answer 19

80% = asymptomatic

hepatomeg + massive splenomeg, lethargy, hypermetabolism, easy bruisiing/bleeding

Question 20

investigative findings in CML

Answer 20

blood film - massive leukocytosis, no excess myeloblasts in bone marrow (<5%)
FISH - phil Chr +ve
inc basophils

Question 21

what is the Philadelphia Chr fusion geen

Answer 21

BCR-ABL

Question 22

what are the different stages of CML

Answer 22

1 - chronic phase. <5%blasts sin BM/blood
Tx = imatinib (BCR_ABL TKI)

2 - accelerated phase. >10% blasts in BM/blood. inc manifestations

3 - blast phase. >20% blasts, resembles acute leukemia, Tx similar to AML