Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Yr 3 - January lectures 19 > Myeloproliferative disorders > Flashcards

Myeloproliferative disorders Flashcards

1
Q

Define chronnic myeloid leukaemia?

A

too many myeloid cells -philadelphia chromosome positive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define: polycythaemia rubra vera/polycythaemia vera

A

too many red cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define: essential thrombocythaemia

A

too many platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define: myelofibrosis

A

excessive fibrosis in the marrow secondary to a probable ET/PRV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Of the myeloproliferative neoplasma which ones commonly overlap?

A

PV, ET and myelofibrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do the majority of MPN have?

A

a genetic abnormality - useful as we can test for them

-if you have a JAK 2 mutation you have either PV, ET or MF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does a mutation in JAK2 cause?

A

activating tyrosine kinase mutation in pseudokinase domain causes disruption of auto-inhibitory effect on tyrosine kinase activity
=> cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

When is polycythaemia vera more common?

A

it increases with age but it is not exclusive to the eldelry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does PV present?

A

symptoms:
- headache
- dizziness
- blurred visions dyspnoea- “sluggish blood”
- fill feeling in head
Signs:
- plethora (excessive blood)
- conjunctival suffusion = redness of the conjunctiva that resembles conjunctivitis, but it does not involve inflammatory exudates
- engorged retinal vessels
- tendency to thrombosis - DVT, MI, CVA
- erythromelalgia
- tendency to bleeding - epistaxis, GI bleeding, CVA
Specific:
- acquagenic pruritis = itching with water
- splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the causes of PV?

A

Hypoxia = normal physiological response to low oxygen
Smoking = most common cause
Lung disease
Cyanotic heart disease
Altitude
certain rare tumours
rare hb variants - bind O2 too tightly
too much or inappropriate EPO (tumours can produce EPO)
spurious = due to reduced plasma volume, so red cell vol appears increased

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the aims in treating PV and ET?

A

Reduce risk of thrombosis and haemorrhage

minimise the risk of transformation to acute leukaemia and myelofibrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the treatments for PV?

A 
venesection to Hct <0.45 = unit of blood removed 
anti-platelets if they have too high platelet count = aspirin 
hydroxycarbamide for thrombocytosis but possibly does increase risk of leukaemic transformation and myelofibrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the prognosis of PV?

A

65% survival with treatment and mortality compared with gen pop is 1.6 fold higher
they have increased risk of leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the epidemiology of ET?

A

most common MPN

  • 1.5-2/100,000
  • Median age 50-55 another peak at 30
  • F>M
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the clinical features of ET?

A 
Mostly asymptomatic diagnosis 
Vascular events 
- thrombosis (arterial >venous) 
- microvascular occlusive symptoms 
=> erythromelalgia 
=> acroparasthesia 
=> digital ischaemia 
=> neurological = TIA, migraine like headache, dizziness
=> vision disturbances = transient blindness, blurred vision, photophobia

platelets affect microcirculation = cause pain in hands and feet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the differential diagnoses for ET?

A 
Cancer
iron deficiency 
acute haemorrhage- infections, inflammatory states 
asplenia 
secondary//reactive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is ET diagnosed?

A

diagnostic criteria
- A1-3 or A1 +3-5
A1=sustained platelet count >450
A2= presence of acquired pathogenic mutation
A3= no other myeloid malignancy, esp PV, PMF, CML or MDS
A4= no reactive cause for thrombocytosis and normal iron stores
A5= bone marrow aspirate and trephine biopsy showing increase megakarocyte numbers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are some independent risk factors of ET?

A

History thrombosis
age >60

prognosis is essentially the same as normal life as long as it is picked up before catastrophic event

19
Q

What is prefibrotic MF like?

A

like ET but with dysplastic megakaryocytes +/- early fibrosis - 10 yr survival is pretty good

20
Q

What are the low risks for MF and how is it treated?

A 
age < 60 
platelets <1500
no prior TED/bleeding 
no cardio risks
no hereditary thrombophilia

Tx
- no cytoreductive therapy
+/- ASA

21
Q

What are the intermediate risks for MF and how is it treated?

A 
platelets<1500
age <60
no TED/bleeding 
CVS risk factors 
here thrombophilia

Tx

  • reduce CVS risk
  • ASA
  • reduce platelets in some with cytoreduction
22
Q

What are the high risks for MF and how is it treated?

A

age >60
platelets>1500
prior TED

Tx

  • ASA
  • cytoreduction to reduce platelets
23
Q

What is cytoreductive therapy?

A

used to reduce the risk of hemorrhage

24
Q

What is ASA?

A

Antithrombotic prophylaxis with aspirin

25
Q

What is the 1st line cytoreductive treatment?

A 
hydroxyurea (chemo agent)
- ribonucleotide reductase inhibitor 
- dose 15mg/kg - proven to reduce counts and TED risk 
SE
- Bone marrow suppression 
- diarrhoea
- leukaemogenic?
- skin cancer
26
Q

What does TED stand for?

A

thromboembolic disorder

27
Q

What is the 2nd line cytoreductive treatment?

A

Anagrelide
- inhibits megakarocyte differentiation and platelet aggregation
SE
- fibrosis - needs bone marrow follow up for MF
- haemorrhage with aspirin
- headache, palps, arrhythmia, HF, anaemia
- elderly with heart disease= CAUTION
- 1/3 discontinuation because of SE

28
Q

What treatment for ET is good in young patients or females of child baring age?

A

low dose pegylated IFNalpha2a

- 30-40% significant decrease in JAK2Mutation allele burden

29
Q

What is the epidemiology of MF?

A

UK incidence - 0.5-1.5 per 100,000
median age = 60
90% are diagnosed after 40yrs
overall median survival is 5 yrs

30
Q

How does MF present?

A

fibrotic marrow - bone marrow fails = Hb falls leading to anaemia
cytopenias
very large spleen

hypermetabolic type symptoms

  • asymptomatic
  • spleen pain
  • fevers, sweats, back pain
  • infections

often poor prognosis
blood transfusions

31
Q

What are the main treatments for MF?

A 
Blood transfusions 
AlloSCT if young and fit
thalidomide
medroxyprogesterone 
Ruxolitinib - JAK inhibitor
32
Q

What are the clinical features of MF?

A 
Marrow failure 
splenomegaly 
hepatomegaly 
hypermetabolic syndrome 
hyperuricaeniia - can get gout from producing lots of uric acid
33
Q

What are the diagnostic criteria for MF?

A

A1 + A2 and any two B criteria
A1= bone marrow fibrosis 3 (0-4 scale)
A2= pathogenetic mutation or absence of both BCR-abl and reactive causes of bone marrow fibrosis

B1 = palpable splenomegaly 
B2= unexplained anaemia 
B3= leuco-erythroblastosis 
B4= Tear drop red cells 
B5= consitutional symptoms 
B6= histological evidence of extramedullary haematopoesis
34
Q

What investigations should be carried out if you suspect MF?

A 
FBC 
bone marrow aspirate and trephine 
Molecular test 
- JAK mutation test (50-60%)
- CALR mutation (40%)
- Mpl mutation (9%)- more severe phenotype, more transfusion dependent
35
Q

What is Ruxolitinib ?

A

oral jak inhibitor = targeted therapy

  • rapid improvement in constitutional symptoms
  • rapid reduction in splenomegaly
  • improvement in blood counts
  • transfusion independence
  • rapid improvement in QoL
  • early data on improved survival

1/3 decrease in spleen vol, decrease in symptoms (anaemia, thrombocytopenia)

Don’t stop it abruptly as it causes ruxolitinib withdrawal syndrome

36
Q

What is CML?

A

Type of myeloproliferative disease
- accumulation of myeloid progenitors (proliferation of myeloid cells)
- high white blood cell count
- large spleen
can transform into acute leukaemia
previously treated with myelosuppressive therapy (hydroxycarbamide), transplantation but NOW imatinib

37
Q

What is the genetic basis of CML?

A

Philadelphia chromosome
- fusion genes that result in a protein with altered activity
Bcr-abl protein has markedly increased activity - abl gene is involved in cell signalling

38
Q

How does imatinib work?

A

revolutionised the treatment for CML

  • inhibits the binding of ATP to ABL tyrosine kinase
  • more similar drugs are being developed to reduce the SE profile
39
Q

Why have newer versions of imatinib needed to be developed?

A

cancers evolve therefore mutations within CML make it resistant to imatinib so next generation BCR-ABL inhibitors have been developed

  • nilotinib
  • dasatinib
  • bosutinib - can cause primary hypertension
  • ponatinib
40
Q

What are the main SE of imatinib?

A

arthralgia

GI upset

41
Q

What are the characteristics of myelodysplasia?

A

disease of the elderly
presents as bone marrow failure - 1 or more of anaemia, neutropenia, thrombocytopenia
chronic myelomonocytic leukaemia has raised monocytes
incidence increases with age
median age is 70

it is not one disease, its a heterogenous clonal disorder of blood cell production - acquisition of a number of heterogeneous changes that sequentially perturb haemopoietic cell fate

42
Q

What are the causes of myelodysplasia?

A

usually no obvious cause
can be secondary to chemotherapy
weak familial risk
rare inherited bone marrow failure syndromes

43
Q

What factors are important to ask in a hx suspicious of myelodysplasia and what examination findings are likely to be present?

A

prior exposure to chemotherapy/radiotherapy
family hx of MDS/AML

dysmorphic features (suggesting congenital bone marrow failure)

44
Q

Where does MDS arise?

A

disorder arises in a haemopoietic stem cells that leads to wonky development manifest by……

  • variably reduced numbers of mature red blood cells, white blood cells, platelets
  • cells produced are not quite right- look abnormal under microscope and function less well
  • primitive cells “blasts” may accumulate as failure to mature normally

cells are less healthy and die quicker

Yr 3 - January lectures 19 (30 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions