myeloid malignancies

Question 1

myeloid malignancies

Answer 1

myeloid origin

myeloid progenitor cells, red cells, platelets, granuolcytes, monocytes

Question 2

AML lineage

Answer 2

myeloiod progenitor cell

proliferation without differentiation

Question 3

AML general points

Answer 3

• leukemic cells don’t differentiate
• bone marrow failure
• rapidly fatal if untreated
• potentially curable

Question 4

CML general points

Answer 4

• leukaemic cells retain ability to differentiate
• proliferation wout bone marrow failure
• survival for few years
• long term survival/possible cure w modern therapies

Question 5

subgroups of acute leukemia

Answer 5

acute myeloblastic leukaemia

acute lymphoblastic leukaemia

Question 6

AML: why does bone marrow failure happen

Answer 6

acute leukemic cells replace bone marrow

Question 7

AML classic triad

Answer 7

anaemia: tired, SOB, heart failure
thrombocytopenia: purpura, mucosal bleeding
neutropenia: infection

Question 8

AML bone marrow aspirate findings

Answer 8

AML = >20% bone marrow is blasts

<20% then myelodysplastic syndrome

Question 9

AML Ix

Answer 9

blood count + blood film 
bone marrow aspirate
cytogenic from blasts
immunophenotyping blast: determine lymphoid or myeloid origin 
CSF if symptomatic

Question 10

RX AML

Answer 10

supportive care: specialist unit, early recognition neutropenic sepsis
anti-leukaemic chemotherapy
SCT
all-trans retinoic acid and arsenic trioxide

Question 11

AML antileukemic chemotherpay

Answer 11

daunorubicin + cytosine arabinoside
high dose cytoisne arabinoside

to induce and consolidate remission

Question 12

AML remission

Answer 12

normal blood count and <5% blasts

Question 13

new developments in AML

Answer 13

targeted antibodies: gentuzumab oozaigimicin
targeted small molecules: midostaurin - tyrosine kinsase inhibitor
new chemo delivery systems: CPX-351

Question 14

CML features

Answer 14

anaemia of chronic disease
splenomegaly 
gout 
weight loss
hyperleukostasis

Question 15

CML hyperleukostasis

Answer 15

high WCC
fundal heamorrhage, venous congestion
alt consciousness
resp failure

Question 16

CML lab features

Answer 16

high WCC
high platelets
anaemia
blood film shows all stages white cell differentiation + inc basophila
bone marrow hypercellular
bone marrow + blood cells contain philadelphia chromosome t(9;22): overproduction of abnormal fusion gene fusion

Question 17

CML treatment

Answer 17

tyrosine kinase inhibitors first line; direct inhibition BCR-ABL (philadelphia chromosome)

transplant in TKI failure

Question 18

myeloprolipherative neoplasm examples

Answer 18

polycythemia vera
essential thrombocythemia
idiopathic myelofibrosis

Question 19

myeloprolipherative neoplasm mutation

Answer 19

JAK2 V617F mutation

JAK2 activation without erythropoetin binding
independant stimulation red cell production

Question 20

polycythemia vera clinical features

Answer 20

headaches
itch 
vascular occlusion 
TIA, stroke
splenomegaly 
plethora (red facies)

Question 21

polycythemia vera lab features

Answer 21

raised Hb and raised haematocrit
tendency to raised WCC + platelets
raised uric acid (risk gout)
increase in red cell mass

Question 22

polycythemia vera Rx

Answer 22

• venesection to lower haematocrit (blood letting)
• aspirin: reduce risk thrombosis
• hydroxycarbamide/alpha interferon
• ruxolitinib (JAK2 inhibitor) in hydroxycarbamide failure

Question 23

polycythemia vera natural history

Answer 23

• stoke and other thromboses if poorly controlled
• bone marrow failure from development 2ry myelofibrosis
• transformation to AML

Question 24

essential thrombocythaemia

Answer 24

myeloproliferative disease with predominant feature of raised platelet count

Question 25

essential thrombocythaemia symptoms

Answer 25

``` thromboses digital ischaemia gout headache mild splenomegaly ```

Question 26

essential thrombocythaemia Mx

Answer 26

aspirin | hydroxycarbamide

Question 27

essential thrombocythaemia progression

Answer 27

can progress to myelofibrosis or AML