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Year 3 - Haematology > Myeloid Malignancy > Flashcards

Myeloid Malignancy Flashcards

1
Q

hwat is the Origin of bone marrow malignancies?

A
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2
Q

what are the different types of Myeloid Malignancy?

A

Acute Myeloid Leukaemia (AML)

Chronic Myeloid Leukaemia (CML)

Myelodysplastic Syndromes (MDS) - one of a group of cancers in which immature blood cells in the bone marrow do not mature, so do not become healthy blood cells

Myeloproliferative Neoplasms (MPN) - a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow

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3
Q

what is the difference between Acute vs Chronic Myeloid Leukaemia?

A

Acute - Bane marrow fills with cells that are failing to differentiate

Chronic - In chronic can produce end cells

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4
Q

what are the Sub groups of Acute Leukaemia?

A

Acute Myeloblastic Leukaemia (AML)

Acute Lymphoblastic Leukaemia (ALL)

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5
Q

describe wht can be seen here?

A

Normal bone marrow under low power

Lots of different cells as it is a bone marrow producing everything you need e.g. neutrophils, myelocyte, early cells, lymphocytes, nucleated red cells

Healthy bone marrow

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6
Q

what is seen here?

A

acute leukaemia replacing the bone marrow leads to bone marrow failure

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7
Q

what are the clinical features of AML?

A

BONE MARROW FAILURE (Triad)

  • Anaemia
  • Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding)
  • Infection because of neutropenia (predominantly bacterial and fungal)
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8
Q

Elderly man

No obvious trauma to arm

Severe thrombocytopenia due to acute myeloid leukaemia

A

Man with acute myeloid leukaemia

Bitten tongue slightly

Leads to ulcer and haematoma around it

Thrombocytopenia and neutropenia

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9
Q

Fungal pneumonia in AML-CXR

Area of consolidation on right side

A

Fungal pneumonia in AML – CXR 24 hours later

Rapid dissemination

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10
Q

Multiple fungal abscesses in AML – Brain MRI scan

A
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11
Q

what are essential investigations done in AML?

A

Blood count and blood film (Blood count will show thrombocytopenia, neutropenia, low BC etc)

Bone marrow aspirate/ trephine - (Diagnose when) Blasts > 20% of marrow cells in acute leukaemia

Cytogenetics (Karyotype) from leukaemic blasts

Immunophenotyping of leukaemic blasts (differentiate between myeloid or lymphoid blast)

CSF examination if symptoms

Targeted molecular genetics for associated acquired gene mutations - e.g. FLT3, NPM1, IDH 1 & 2

Increasing use of extended Next Generation Sequencing (NGS) myeloid gene panels in AML - multiple genes analysed

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12
Q

what is the treatment of AML?

A

Supportive care

Anti-leukaemic Chemotherapy (3 stages in anti-leukaemic chemotherapy):

Remission induction - to achieve remission (1-2 cycles):

  • normal blood counts and less than 5% blasts
  • Daunorubicin & cytosine arabinoside (DA)
  • Gemtuzumab Ozogamicin
  • CPX-351

Consolidation (1-3 cycles):

  • High dose cytosine arabinoside
  • Allogeneic stem cell transplantation - to consolidate remission/potential cure (Allogeneic stem cell transplantation Is the best treatment (stem cells from someone else))

Maintenance (New) - Maintenance is where you give low levels of treatment for a long time to prevent relapse:

  • Midostaurin (FIT3 inhibitor)
  • Oral azacitidine (hypomethylating agent)

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in low risk Acute Promyelocytic Leukaemia – ‘Chemo –free’ – high cure rate ~ 90%

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13
Q

what are some New developments in AML?

A

Targeted antibodies: - Gemtuzumab Ozogamicin: anti-CD33 with Calicheomycin (Mylotarg)

Targeted small molecules: - Midostaurin: tyrosine kinase inhibitor inhibiting FLT3

New chemotherapy delivery systems - CPX -351

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14
Q

how has the survival of AML changed?

Steady improvement in survival

A

More recent data

Age is important in AML

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15
Q

onto Chronic Myeloid Leukaemia

A

Proliferation with differentiation

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16
Q

what do you get in CML?

A

Anaemia - Anaemia not because of bone marrow failure but anaemia of chronic disease

Splenomegaly, often massive (proliferation in spleen)

Weight loss

Hyperleukostasis - Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure.

Gout

17
Q

what does the blood levels look like in CML?

A

A little bit anaemic

Platelets high

Not made up of blasts, most of them are other myeloid cells

18
Q

what does CML look like in histology?

A

Looks like normal bone marrow but just a lot more of it

19
Q

what are the labratory features of CML?

A

High WCC (can be very high )

High platelet count

Anaemia

Blood film shows all stages of white cell differentiation with increased basophils

Bone marrow is hypercellular

Bone marrow and blood cells contain the Philadelphia chromosome - t(9;22) - Nearly all patients had a Small chromosome 22

20
Q

what is the philadelphia chromosome seen in CML?

A

Exchange of genetic material

A bit of chromosome 9 is put on chromosome 22 and a bit of 22 is put on chromosome 9 so you have a big long chromosome 9 and a short chromosome 22 and this short chromosome puts together 2 genes which shouldn’t be together

Overproduction of this abnormal fusion gene on the Philadelphia 22 (small chromosome 22) causes the disease

21
Q

what is the treatment of CML?

A

Tyrosine Kinase Inhibitors (TKIs):

  • Imatinib (Glivec)
  • Dasatinib (Sprycel)
  • Nilotinib (Tasigna)
  • Busitinib
  • Ponatinib

Direct inhibitors of BCR-ABL : First line in all patients nowadays

Allogeneic Transplantation (few now)- Only in TKI failures – can fail due to additional mutaitons in leukaemic cells or patients don’t take drugs

22
Q

how do the Tyrosine Kinase Inhibitors (TKIs) for the treatment of CML work?

A

Mode of action in TKI (Imatinib) inhibition of BCR-ABL

Exactly how the tyrosine kinase inhibitors work

Uses ATP to put phosphate groups on downstream proteins - Inmatinib inhibit the blocks the phosphorylation process

23
Q

what are Myeloproliferative Neoplasms
(MPN)?

A

Myeloproliferative neoplasms (MPN) are cancers that start in the bone marrow, where blood cells are made.

In MPN, the bone marrow makes too many of one or more types of blood cells (red blood cells, white blood cells and/or platelets). These cells change the thickness of the blood. Sometimes they don’t work properly. They also crowd the bone marrow and then it can’t make enough healthy blood cells.

There are seven types of MPN, diagnosed using blood tests and a bone marrow biopsy. Some forms can transform into other types of MPN or into acute myeloid leukaemia.

24
Q

what are the types of Myeloproliferative Neoplasms
(MPN)?

A

Polycythaemia Vera (PV)

Essential Thrombocythaemia (ET)

Idiopathic Myelofibrosis (often advanced stage of PV and ET)

25
Q

what do myeloproliferative disorders occur?

A

A mutation of a particular gene (a segment of DNA that makes proteins) known as Janus kinase 2 (JAK2) is found in a large proportion of people with MPNs. The exact meaning of this mutation remains unclear but it appears to play a role in the overproduction of blood cells seen in these disorders

JAK2 V617F mutation in 95% of PV

50% of ET & myelofibrosis

The JAK2 V617F mutation is an acquired, somatic mutation present in the majority of patients with myeloproliferative cancer (myeloproliferative neoplasms) i.e. nearly 100% of patients with polycythemia vera and in about 50% of patients with essential thrombocytosis and primary myelofibrosis (also known as idiopathic myelofibrosis)

26
Q

what are the clinical features of PV?

A

Headaches

itch

vascular occlusion

thrombosis

TIA, stroke

Splenomegaly

a type of blood cancer. It causes your bone marrow to make too many red blood cells. These excess cells thicken your blood, slowing its flow, which may cause serious problems, such as blood clots

27
Q

what are the labratory features of PV?

A

A raised haemoglobin concentration and haematocrit

A tendency to also have a raised white cell count and platelet count

A raised uric acid

A true increase in red cell mass when the blood volume is measured

Proliferation of red cells mainly but also maybe white cells and platelet count may be raised also

28
Q

what is the typical blood count seen in PV?

A

Dramatic raise in haemoglobin

Also high haematocrit

29
Q

what is the treatment of PV?

A

Venesection to keep the haematocrit below 0.45 (removing blood)

Aspirin (to reduce risk of thrombosis)

Cytoreduction - Hydroxcarbamide (HC)/Alpha Interferon (used to bring platelet and WC count down)

Ruxolitinib(JAK2 inhibitor) in HC failures with systemic symptoms

30
Q

what is the natural history of PV?

A

Stroke and other arterial or venous thromboses if poorly controlled

Bone marrow failure from the development of secondary myelofibrosis

Transformation to AML (Additional genetic mutation can lead to the progression to AML)

31
Q

what is Essential thrombocythaemia (ET)?

A

exactly same process again but htis time the phenotype of the disease leads to a high production of platelets

  • Myeloproliferative disease with predominant feature of raised platelet count
  • 50% positive for JAK2V617F mutation
  • 25% positive for calreticulin (CALR) mutation

an uncommon disorder in which your body produces too many platelets. Platelets are the part of your blood that sticks together to form clots. This condition may cause you to feel fatigued and lightheaded and to experience headaches and vision changes It also increases your risk of blood clots.

32
Q

what are the symptoms of essential thrombocythaemia (ET)?

A
  • Symptoms of arterial and venous thromboses, digital ischaemia, gout, headache
  • Mild splenomegaly
33
Q

what is the treatment of ET and hwat may it progress to?

A
  • Treated with aspirin and hydroxycarbamide or anagrelide (Again prevent risk of thrombosis)
  • Can progress to myelofibrosis or AML
34
Q

what is shown here?

A

Marked thrombocytosis with giant platelets in ET

Thrombocytosis is a condition in which there is an excessive number of platelets in the blood. Platelets are blood cells in plasma that stop bleeding by sticking together to form a clot. Too many platelets can lead to certain conditions, including stroke, heart attack, or a clot in the blood vessels

Year 3 - Haematology (15 decks)

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