Haematology 10: CML And Myeloproliferative Disorders

Question 1

What is the difference between relative (pseudo) and true Polycythaemia ?

Answer 1

Relative: low plasma volume, normal Hb, high haematocrit
True: normal plasma volume, high Hb, high haematocrit

Question 2

List 4 myeloproliferative disorders ?

Answer 2

Polycythaemia Vera
Essential thrombocytopenia
Primary myelofibrosis
CML

Question 3

If a person has 18% myeloblasts do they have

A) MDS
B) CML
C) ALL
D) AML

Answer 3

A)-MDS

MDS is 5-19% blasts
AML is 20% + blasts
CML has fully differentiated but overproduced Myelocytes
ALL is lymphocytic not myeloid

Question 4

What is the physiological role of Tyrosine kinases ?

Answer 4

Phosphorylate genes that cause cell growth (increased myeloid cell production)

They do not affect differentiation just proliferation

Question 5

Which gene is most commonly mutated in polycythaemia rubra Vera ?

Answer 5

JAK2

Question 6

What affect does JAK2 mutation have on erythropoeisis ?

Answer 6

JAK2 normally phosphorylates EPO receptors in response to EPO.
When mutated this process is constitutively activated so erythropoiesis occurs without regulation by EPO

Question 7

What is the most pathognomonic sign/symptom of polycythaemia rubra Vera ?

Answer 7

Aquatic pruritus- hot baths causing itching

Question 8

Give 2 treatments of polycythaemia rubra Vera ?

Answer 8

Hydroxycarbamide

Venesection

Question 9

Which leukaemia is associated with massive Splenomegaly and hepatomegaly ?

Answer 9

CML

Question 10

What are the 3 phases of CML ?

Answer 10

Chronic phase
Accelerated phase
Blast crisis

Question 11

What is the most common chromosomal abnormality in CML ?

Answer 11

t(9;22)- BCR-ABL

Philadelphia chromosome

Question 12

Which modality is useful for monitoring treatment response in CML ?

Answer 12

RT-PCR (reverse transcriptase)

Question 13

What is the 1st line treatment for CML ?

Answer 13

Imatinib (tyrosine kinase inhibitor)

Question 14

Which test allows you to tell the difference between reactive neutrophilia and leukaemia neutrophilia (CML) ?

Answer 14

Leukocyte alkaline phosphatase

Low in CML
Normal/ High in reactive neutrophilia

Question 15

list appropriate causes of raised erythropoietin

Answer 15

high altitude
hypoxic lung disease
cyanotic heart disease
high-affinity haemoglobin

Question 16

list Philadelphia negative myeloproliferative neoplasms

Answer 16

PV
ET (essential thrombocytopaenia)
PMF (primary myelofibrosis)

Question 17

list different myeloid malignancies

Answer 17

AML
Myelodysplasia
Myeloproliferative disorders
CML

Question 18

list different lymphoid malignancies

Answer 18

precursor cell malignancy eg ALL (B and T cell)

mature cell malignancy eg CLL, MM, lymphoma (H+ NH)

Question 19

what does a mutation in TK genes result in

Answer 19

expansion of mature cells

Question 20

what mutations are associated with myeloproliferative disorders

Answer 20

JAK 2 (V617F) - PV (100%), ET, PMF
Calreticulin - ET and PMF
MPL - ET

Question 21

symptoms of PV

Answer 21

hyperviscocity:
- headaches, light headedness, stroke, visual dist, fatigue, dyspnoea

increased histamine release:
- aquagenic pruritus, peptic ulceration

Question 22

symptoms of ET

Answer 22

bimodal (30, 55)
incidental finding in 50%

thrombosis:
- CVA, gangrene, TIA, DVT, PE

bleeding:
- mucous membranes and cutaneous

Question 23

treatment for ET

Answer 23

aspirin
hydroxycarbamide (antimetabolite that suppresses cell turnover)
anagrelide (inh pl but rarely used)

Question 24

prognosis for ET

Answer 24

normal life span in many
leukaemic transformation in 5% over 10 yrs
myelofibrosis uncommon

Question 25

define myelofibrosis

Answer 25

clonal myeloproliferative disease associated with reactive BM fibrosis extra medullary haematopoiesis 60-70 yrs

Question 26

symptoms of myelofibrosis

Answer 26

``` cytopaenias thrombosis splenomegaly (MASSIVE) hepatomegaly hypermetabolic state (B symptoms + hyperuricaemia) ```

Question 27

signs of myelofibrosis

Answer 27

``` leukoerythroblastic tear drop poikilocytes giant platelets circulating megakaryocytes dry tap BM trephine biopsy - increased reticulin or collagen fibrosis spleen - intramedullary hematopoiesis ``` JAK 2/ CALR mutation

Question 28

treatment for myelofibrosis

Answer 28

``` supportive - RBC and pl transfusion cytoreductive therapy - hydroxycarbamide ruxolitinib - JAK2 inhibitor allogenic SC transplantation splenectomy ```

Question 29

features of CML

Answer 29

more common in M 40-60 yrs radiation exposure = RF chronic phase (5-6 yrs) - accelerated (6-12 m) - blast crisis (3-6m) PHILADELPHIA CHROMOSOME - 22q, Bcr-abl, codes for a tyrosine kinase

Question 30

presentation of CML

Answer 30

``` lethargy hypermetabolism thrombotic event mono-ocular blindness CVA bruising bleeding MASSIVE splenomegaly /hepatomegaly ``` massive leukocytosis Hb and pl normal/ raised blood film: neutrophils, myelocytes not blasts, basophilia

Question 31

treatment for CML

Answer 31

1st gen tyrosine kinase inhibitor - Imatinib 2nd gen - Dasatinib, Nilotinib 3rd gen - Bosutinib Allogenic SC transplant