Chronic myeoproliferative disorders and chronic myeloid leukaemia.

Question 1

define chronic myeloproliferative disorders.

Answer 1

long term myeloid lineage cells hyper proliferate.

Question 2

what blood cancer can chronic myeloproliferative disorders progress too

Answer 2

leukaemia

Question 3

what cells are contained within stem cells

Answer 3

erythrocytes
Granulocytes (neutrophil, eosinophil and basophil)
Megakaryocytes (platelets)

Question 4

define polycythaemia vera

Answer 4

increased RBC, +/- neutrophils and platelets.

Question 5

deine essential thrombocthaemia

Answer 5

increased platelets

Question 6

define myelofibrosis

Answer 6

proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue

Question 7

3 myleoprolifertive disorders

Answer 7

myelofibrosis
polycathaemia vera
essential thrombocythaemia.

Question 8

symptoms of polycythaemia vera

Answer 8

Insidious, itching, plethoric face, headache, general malaise, tinnitus, peptic ulcer, gout-uric acid crystals, gangrene of the toes, plethora, gangrene, engorged retinal veins, spleenomegaly.

Question 9

how is polycathaemia vera diagnosed

Answer 9

Persistent increased Hb/hct (haemoatocrit) >0.5

Question 10

what is the difference between relative and absolute polycathemia.

Answer 10

relative is where RBC appear high in comparison to plasma which has decreased in volume happens in dehydrated e.g. alcoholic)
absolute is where the level of RBC is down.

Question 11

what is the difference between primary and secondary polycythaemia.

Answer 11

primary is in the bone marrow, secondary is due to another factor such as living in high altitudes,

Question 12

what is the first line of tests if you suspect polycythaemia.

Answer 12

FBC
Ferritin
EPO level
UE/LFT

Question 13

what is the only primary cause of polycythaemia

Answer 13

polycythaemia vera

Question 14

what are the secondary causes of polycythaemia.

Answer 14

central hypoxic process
renal disease -EPO
drug associated- androgen preparations
Congenital- high oxygen affinity, erthythrpoeitien receptor mediated.
Idiopathic erythrocytosis

Question 15

what are the second line tests for polycthaemia

Answer 15

CXR-chest xray
ABG
USS-abdomen for spleenomegaly.

EPO Normal- JAK2 mutation, Bone marrow examination, EXON 12 mutation.

Question 16

what change takes place in the JAK2 mutation.

Answer 16

G-to-T mutation at nucleotide 1849

Phenylalanine for valine at 617 in protein (V617F)

Question 17

how does the JAK2 mutation cause myeloproliferative disorders

Answer 17

EPO binds to receptor with JAK2 and phosphorylation causes DNA replication, but with mutation receptor in activated without EPO.

Question 18

Treatment for polycythaemia vera

Answer 18

venesection (remove RBC) aim to get haemocrit 0.45.

Aspirin.

Question 19

causes of reactive (secondary) thrombocytosis

Answer 19

surgery, infection, inflammation, malignancy, iron deficiency, hyposplenism, haemolysis, drug induced (steroids or adrenaline, TPO), rebound post chemo

Question 20

what are the first line investigations of thrombocytosis

Answer 20

1. FBC and film
2. Ferritin
3. CRP
4. CXR
5. ESR

Question 21

what are the second line investigations for thrombocytosis

Answer 21

• JAK2
• CALR
• ? Bone marrow biopsy
• Extensive search for secondary cause

Question 22

what is CALR

Answer 22

• cell signalling protein produced in ER (endoplasmic Reticulin) and found in myeloid progenitors.

Question 23

treatment for thrombocytosis

Answer 23

Aspirin 75mg daily- inhibits platelets.

Cytoreduction (only if High risk)

Question 24

what is cytorecustion (used in thrombocytosis treatment)

Answer 24

Hydroxycarbamide- antifolate- reduced DNA synthesis.

Question 25

Clinical presentation of myelofibrosis.

Answer 25

pancytopenia- deficney in all 3 blood cell types | fever, night sweats and weight loss.

Question 26

spleenomegaly is a complication of which 2 of the 3 myeloproliferative disorders

Answer 26

polycathemia and myelofibrosis

Question 27

what are the first line investigations for myelofibrosis

Answer 27

FBC and film

Question 28

how is myelofibrosis diagnosed

Answer 28

blood film, bone marrow results, JAK mutation and CALR mutation.

Question 29

how do you measure spleen size

Answer 29

from mid clavicular line at the costal margin to the furthest margin at which the spleen can be felt.

Question 30

causes of spleenomegaly

Answer 30

``` Cancer Hameatological -myelofibrosis. Infection Congestion-liver/portal disease Autoimmune Glycogen storage disorders Other- amyloid. ```

Question 31

Treatment for myelofibrosis

Answer 31

Supportive care- EPO injections. Anaemic (blood transfusion), platelets transfused. JAK2 Inhibitors- helps shrink spleen. Bone marrow Transplant

Question 32

which of the 3 myeloporliferative disorders has poor prognosis

Answer 32

myelofibrosis

Question 33

what are the clinical features of chronic myeloid leukaemia

Answer 33

leukocytosis- lots of WBC. anaemia. splenomegaly.

Question 34

symptoms of chronic myeloid leukaemia

Answer 34

* Abdominal discomfort:Splenomegaly * Abdominal pain: Splenic infarction * Fatigue: Anaemia, catabolic state * Venous occlusion: Retinal vein, DVT, priapism (continuous erection cause infract) * Gout- Hyperuricaemia

Question 35

treatment for chronic myeloid leukaemia. | chronic and acute phase

Answer 35

chronic phase- Low dose oral cytotoxic drugs (busulphan, hydroxycarbamide). Acute transformation- intensive chemotherapy Allogenic bone marrow transplant

Question 36

What common translocation increases the chance of developing chronic myeloid leukaemia

Answer 36

* ABL- chromosome 9 * BCR- chromosome 22 * Translocation results in these 2 sitting next to each other- oncogene, which codes for tyrosine kinase tells cells to hyperprolifearte, which causes anaemia.

Question 37

which drug inhibits the Philadelphia chromosome

Answer 37

• Gleevac (imantinib)- block the active site in the bcr-abl tyrosine kinase.

Question 38

BCR-ABL mutations confer resistance to which drug used to treat chronic myeloid leukaemia

Answer 38

-Imatinib.

Question 39

what are the 2 phases of chronic myeloid leukaemia

Answer 39

chronic | acute transformation.