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Y3 immunology and haematology > myeloid malignancy > Flashcards

myeloid malignancy Flashcards

1
Q

what cells do myeloid malignancies involve

A

red cells
platelets
granulocytes
monocytes

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2
Q

what happens to the cells in AML

A

proliferation w/o differentiation

involves myeloid progenitor cells

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3
Q

what are the 4 main myeloid malignancies

A

acute myeloid leukaemia (AML)

chronic myeloid leukaemia (CML)

myelodysplastic syndromes (MDS)

myeloproliferative neoplasms (MPN)

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4
Q

acute vs chronic myeloid leukaemia

A

ACUTE:

  • leukaemic cells don’t differentiate
  • bone marrow failure
  • rapidly fatal if untreated - ~50% of pts survive the yr
  • potentially curable

CHRONIC:

  • leukaemia cells retain ability to differentiate
  • proliferation w/o bone marrow failure
  • survival for a few yrs previously
  • long term survival/possible cures w/ modern therapy
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5
Q

what can be seen here

A

normal bone marrow

heterogeneity of cells

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6
Q

what can be seen here

A

AML

useless, immature cells and no differentiation

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7
Q

clinical features of AML

A

bone marrow failure (triad)

  • anaemia (fatigue, SOB, HF)
  • thrombocytopenic bleeding (purpura and mucosal membrane bleeding)
  • infection - due to neutropenia, predominantly bacterial and fungal
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8
Q

essential investigations for AML

A

blood count and film
bone marrow aspirate/trephine
- blasts >20% of marrow cells in acute leukaemia
cytogenetics (karyotype) from leukaemic blasts
immunotyping of leukaemic blasts
CSF examination if symptoms

targeted molecular genetics for associated acquired mutations e.g. FLT3 and NPM1

increasing use of extended next generation sequencing myeloid gene panels

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9
Q

what is important for getting prognostic info about AML

A

cytogenetics (karyotype) - looks for growth abnormalities in the leukaemia cells

e.g. abnormality where there is exchange of material between Chr 15 and 17 –> acute myeloid leukaemia, >90% of pts cured

one whole loss of Chr 5 and one whole loss of Chr 7 and other bits missing = complex karyotype –> probably incurable in all pts

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10
Q

what is immuophenotyping used for

A

use antibodies to identify the leukaemic blasts as myeloid or lymphoid

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11
Q

CSF examination in AML

A

done when you think pts have CNS involvement

more common in children w/ AML than adults

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12
Q

treatment of AML

A 
supportive care
anti-leukaemic chemotherapy
-remission induction
-consolidation
-maintenance (new)
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13
Q

anti-leukaemic chemotherapy - remission induction

A

to achieve remission - 1-2 cycles
remission = normal blood counts and <5% blasts
- daunorubicin and cytosine arabinoside (DA)
- gemtuzumab ozagamicin
- CPX-351

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14
Q

anti-leukaemic chemotherapy - consolidation

A

1-3 cycles

  • high dose cytosine arabinoside
  • allogenic stem cell transplantation - to consolidate remission/potential cure
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15
Q

anti-leukaemic chemotherapy - maintenance

A

low level treatment for a long period of time to prevent relapse

midostaurin (FLT3 inhibitor)

oral azacitidine (hypomethylating agent)

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16
Q

treatment of low risk acute promyelocytic leukaemia

A

chemotherapy free regimen

all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)

high cure rate ~90%

17
Q

clinical features of CML

A

anaemia (of chronic disease rather than bone marrow failure)
splenomegaly - often massive
weight loss (hypercatabolic state)
hyperleukostasis - fundal haemorrhage and venous congestion, altered consciousness, cardiac and resp failure
gout (due to lots of proliferation and lots of uric acid production)

18
Q

CML blood count

A

high WCC
low Hb
normal MCV
high plts

high neuts
normal lymphs
high monos
high eos - hallmark of CML
high basos
high blasts
high promyelocytes
high myeloctes
high metamyelocytes
- looks like the bone marrow has been moved out of the blood 
high nucleated RBC
19
Q

laboratory features of CML

A

high WCC - can be very high
high platelet count
anaemia

blood film shows all stages of WBC differentiation w/ increased basophils
bone marrow is hypercellular
bone marrow and blood cells contain the Philadelphia chromosome - t(9;22)

20
Q

Philedelphia chromosome

A

translocation where a bit of chromosome 9 is put onto 22 and vice versa

puts BCR gene next to ABL gene (breakpoint plus abelson oncogene)

BCR-ABL is produced as a protein
overproduction of abnormal fusion gene leads to the leukaemia

21
Q

treatment of CML

A

tyrosine kinase inhibitors of BCR-ABL:

  • imatinib (glivec)
  • dasatinib (sprycel)
  • nilotinib (tasigna)
  • bositinib
  • ponatinib

direct inhibitors of BCR-ABL): 1st line in all pts

allogenic transplantation - few now, only in TKI failures

22
Q

how do TKI inhibitors of BCR-ABL work

A

inhibits tyrosine kinase binding domain

blocks phosphorylation process of tyrosine

stops downstream process that drives cml

23
Q

what are the 3 main myeloproliferative neoplasma

A

polycythaemia vera (PV)

essential thrombocythaemia (ET)

idiopathic myelofibrosis - often advanced stage of PV and ET

24
Q

mutations in MPN

A

JAK2 V617F gene mutation in 95% of PV - marked by red cell production
50% of ET and myelofibrosis

CALR mutation in 25% of ET

25
Q

what happens as a result of the mutations in MPN

A

normal JAK2 - w/o erythropoietin there is no signal, when erythropoietin binds to JAK2 receptor there is phosphorylation of the downstream proteins and you get activation and red cell proliferation and production

mutation w/ JAK2 - even w/o erythropoietin signal there is independent stimualtion of red cell produciton

26
Q

clinical features of PV

A 
headaches
itch
vascular occlusion
thrombosis
TIA, stroke - high haematocrit 
splenomegaly - high red cell proliferation
27
Q

laboratory features of PV

A

raised Hb conc and raised haematocrit

tendency to also have raised WCC and plt count

raised uric acid

true increase in red cell mass when the blood vol is increased

28
Q

normal haematocrit levels and levels for investiagtions

A

NORMAL:
M 45%/0.45
F 43%/0/43

INVESTIGATE IF:
M >52%
F >48%

29
Q

PV typical blood count

A 
high WCC
high Hb
high HCt
low MCV
high plts
high neuts
normal lymphs
normal monos
normal eos
high basos

film: microcytosis: large and abnormal; platelets present

30
Q

treatment of PV

A

venesection to keep the haematocrit <0.45

aspirin - reduce risk of thrombosis

cytoreduction: hydroxycarbamide (HC)/alpha interferon (reduce WCC and plts)

ruxolitinib (JAK2 inhibitor) in HC failures w/ systemic symptoms

31
Q

natural hx of PV

A

stroke and other arterial/venous thromboses if poorly controlled

bone marrow failure from development of 2y myelofibrosis

transformation to AML

32
Q

what is ET

A

myeloproliferative disease w/ predominant feature of raised platelet count

33
Q

mutations in ET

A

50% +ve for JAK2V617F mutation

25% +ve for calreticulin (CALR) mutation

34
Q

clinical features of ET

A

arterial and venous thromboses

digital ischaemia

gout

headache

mild splenomegaly

35
Q

treatment of ET and complications

A

aspirin and hydroxycarbamide or anagrelide

can progress to myelofibrosis or AML

Y3 immunology and haematology (20 decks)

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