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Year 3 - Clinical Science and Professionalism > Leukaemia > Flashcards

Leukaemia Flashcards

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1
Q

Define leukaemia

A
  • A cancer of haemopoietic cells usually associated with increased numbers of white blood cells in the bone marrow or the blood
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2
Q

What are the four types of leukaemia

A
  1. Acute lymphoblastic leukaemia (ALL)
  2. Acute myeloid leukaemia (AML)
  3. Chronic myeloid leukaemia (CML)
  4. Chronic lymphocytic leukaemia (CLL)
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3
Q

describe normal blood cell development from a haematopoietic system

A
  • Start with haemopoietic stem cell – called a stem cell can divide into lymphoid progenitor or myeloid progenitor
  • Lymphoid progenitor differentiates into B and T lymphocyte
  • Myeloid progenitor divides into neutrophils, eosinophils, basophils, monocyte, platelets, red cell
  • B lymphocytes – have an antibody that is designed to recognise an antigen
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4
Q

Where does acute lymphoblastic leukaemia begin

A
  • Acute lymphoblastic leukaemia occurs at the lymphoid progenitor stage – stuck at this stage and makes lots of copies of lymphoid progenitor
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5
Q

Where does acute myeloid leukaemia begin

A
  • Acute myeloid leukaemia occurs at the myeloid progenitor stage - stuck at this stage and makes lots of copies of myeloid progenitor
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6
Q

Where does chronic lymphoblastic leukaemia begin

A
  • Chronic lymphoblastic leukaemia occurs at naïve B lymphocyte
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7
Q

Where does lymphoma begin

A
  • Lymphomas occurs at T lymphocyte (happens in the lymph nodes) and B lymphocytes
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8
Q

Where does myeloma begin

A

Myeloma occurs at plasma cell – cancer of plasma cells

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9
Q

where do blood cells come from

A
  • Bone marrow
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10
Q

Where do blood cells come from in adults

A
  • In adults it is mainly in the hip bone, makes all the cells that float in the peripheral blood
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11
Q

What lab tools are diagnosed for haematological malignancies

A

Morphology

  • Blood film
  • Bone marrow biopsy – look at the bone marrow and see if we are seeing normal development

Immunophenotyped
- Flow cytometry

Genetic and molecular features

  • Chromosome abnormalities: G banding and FISH
  • Gene point mutations, insertions/deletions: PCR based
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12
Q

What does flow cytometry distinguish between

A
  • Cancerous from normal tissue

- Different types of haematological malignancies

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13
Q

describe how flow cytometry work

A
  • Lets say we know CD20 is a marker on a cell surface that is normally in lymphoid cells and not myeloid cells
  • Use an antibody that links to CD20 – attached to a fluorescent
  • Then the laser would measure the fluorescent
  • Picking up how many cells have CD20 on the surface
  • Compare to the normal ranges
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14
Q

How does G banding (genetic and molecular tests) work and what is it used for

A
  • Used to detect chromosomal abnormalities

- Cells are cultured for a short time and then are stopped at metaphase and coloured by Giemsa

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15
Q

How does FISH (fluorescence in situ hybridization)

A
  • Does not need to be used with cells in metaphase
  • Technique using fluorescent probes to detect a specific DNA sequence
  • Can identify chromosomal translocations or gains or losses of regions in the genome
  • Need to know what your looking for whereas cytogentics you can see what abnormalities are there
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16
Q

What is a mutation

A

Change in the DNA sequence

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17
Q

What does a mutation do

A
  • If the change affects the protein sequence and function of the translated protein can contribute to disease cancer
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18
Q

How are mutations detected

A
  • Detected by sequencing technologies
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19
Q

What is acute leukaemia characterised by

A
  • Characterised by the accumulation of large numbers of undifferentiated cells called blasts in the bone marrow
  • Block in differentiation
  • These blasts rapidly overwhelm normal blood cells and then spill into the peripheral blood
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20
Q

What are the two types of acute leukaemia

A

acute myeloid leukaemia

acute lymphoid leukaemia

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21
Q

What are the signs and symptoms of acute leukaemias: AML, ALL

A
  • Signs and symptoms of bone marrow failure
  • anaemia = tiredness, shortness of breath
  • WCC – infections if low or leucostasis if high, the blood viscous sticky/cloggy causing problems with smooth blood flow in vessels leading to stroke/confusion
  • Low platelets – bleeding and bruising
  • Aggressive/fast growing/fatal if untreated
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22
Q

What causes acute myeloid leukaemia (AML)

A
  • Associated with T(15:17) fusion of PML and RARA
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23
Q

Who does acute myeloid leukaemia (AML) tend to affect

A

– occurs in older people

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24
Q

Describe the presentation of acute myeloid leukaemia (AML)

A

Usually presents with Disseminated intravascular coagulation or thrombocytopenia

Bone marrow failure
- Neutropenia, fever, pneumonia, fungal infection, thrombocytopenia, bleeding, anaemia

Infiltration
- Hepatomegaly, splenomegaly, gum hypertrophy, skin involvement, CNS involvement (rare)

Elevated white blood cell - Blasts from the bone marrow spilling into the peripheral blood
- Causes leukostasis(headache, stroke, confusion)

Bone pain
– blasts rapidly dividing in the bone marrow

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25
Q

How do you diagnose acute myeloid leukaemia (AML)

A
  • abnormal FBC – low haemoglobin or high, or low Whtie Cell Count /low platelets
  • Blast cells can be found in the peripheral blood
  • Diagnosis depends on the bone marrow biopsy, immunophenotyping and molecular methods - AUER RODS are present in the bone marrow biopsy
  • raised urate and LDH
  • clotting (AMPL- can cause abnormal clotting)
  • Immunophenotyping (flow cytometry)– CD34+ (marker of immature myeloid cell)
  • Cryogenics – 7q – abnormalities on chromosome 7
  • Mutations FLT3
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26
Q

what does acute myeloid leukaemia (AML) look like in a blood film and on a biopsy

A
  • Elongated structures – grouping of granules

- Auer rods present on a biopsy

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27
Q

How do you treat acute myeloid leukaemia (AML)

A
  • Anaemia = blood transfusion
  • Thrombocytopenia = platelet transfusion
  • Neutropenia (need to be treated ASAP if temperature) = prophylactic antibodies and prompt treatment of neutropenic sepsis (temperature greater than 30 degrees, neturophils) with broad spectrum antibiotics
  • Tumour lysis (renal failure, high potassium, high urate, high phosphate, low calcium); fluids = allopurinol, rasburicase
  • Lecuostasis(really high white cell count): emergency venesection or leucopharesis

Currently

  • Intensive chemotherapy
  • Allogenic stem cell transplant
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28
Q

what do cytogenetics matter in acute myeloid leukaemia (AML)

A
  • These matter in terms of progressive free survival years
  • Thus they impact the abnormalities on outcome in AMP

Patietns are risk stratified based on cytogenetics and mutations

  • Good risk – 4 cycles of intensive chemotherapy
  • Intermediate/poor risk – chemotherapy to remission then allogenic transplant
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29
Q

What does it mean for treatment if patients have good cytogenetics versus poor cytogenetics in acute myeloid leukaemia (AML)

A
  • Good risk – 4 cycles of intensive chemotherapy

- Intermediate/poor risk – chemotherapy to remission then allogenic transplant

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30
Q

What chemotherapy is used for acute myeloid leukaemia (AML)

A
  • Has been no new drugs for standard AML since 1960s and 1970s
  • usually a combination of daunorubicin and cytarabine - anti metabolites interfere with DNA synthesis
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31
Q

what cells are affected by chemotherapy for Acute myeloid leukaemia

A

Affects cells that have a high turnover

  • Leukaemia cells
  • Normal cells such as hair cells
  • cells of the gut and intestinal tract
  • Bone marrow
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32
Q

What are the two treatment options for Acute myeloid leukaemia (AML)

A
  • Chemotherapy

- Allogenic bone marrow transplant

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33
Q

what do you do with the bone marrow cells will having chemotherapy

A
  • Auto – give back your own stem cells - Mainly used in myelomas and lymphomas – use heavy chemo to wipe out the bone marrow
  • Allo – give back someone’s elses stem cells – can be used as treatments for acute leukaemia’s.- use someone elses stem cells
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34
Q

What are the two types of allogenic transplant (treatment for Acute myeloid leukaemia (AML))

A
  • Myeloablative

- reduced intensity

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35
Q

describe the two types of allogenic transplant (treatment for Acute myeloid leukaemia (AML))

A
  • Myeloablative – wipe out BM completely
  • Reduce intensity: make some room in BM for new stem cells – don’t wipe out BM completlety, just give some chemotherapy – kill the tumour cells, immune reaction against residual tumour cells
36
Q

How does an allogenic transplant work

A

Allogeneic transplant works via immune reaction against residual tumour cells (though conditioning chemoradiotherapy can help kill AML cells).

37
Q

how can you harvest bone marrow cells

A
  • Collect from the bone marrow – done under GA

- Or can give someone GCSF

38
Q

How does G-CSF work

A
  • Given to the donor or patient subcut for 4 days – collect day +5
  • Mobilises CD34+ stem cells into peripheral blood
  • Collected by leucaphresis
  • No GA
  • No evidence of late haem effects for donors
39
Q

What does survival depend on in AML

A
  • Depends to cytogenic risk group
40
Q

How many patents survive AML

A
  • 50% of children and young adults can expect a long-term cure
  • Less than 10% of patients over 70 can expect a long-term remission
41
Q

What is acute promyelocytic leukaemia (AMPL)

A
  • Subtype of AML
42
Q

What is the characteristic of acute promyelocytic leukaemia (AMPL)

A
  • Characteristic morphology of cells (hypergranular promyelocytes)
43
Q

What is the presentation of acute promyelocytic leukaemia (AMPL)

A
  • Present with abnormal clotting – sevre bleeding or clots
44
Q

What causes acute promyelocytic leukaemia (AMPL)

A
  • T15:17 – fusion of PML and RARA to generate PML-RARA oncoprotein
45
Q

How do you treat acute promyelocytic leukaemia (AMPL)

A
  • Treatment involves ATRA/Arsenic/anthracyclines

- Very treatable with remission rates of greater than 90%

46
Q

What is a Hickman line and when is it used

A
  • Need to do lots of blood tests
  • They go into the larger veins and can stay in or weeks and months
  • Look for clots and infections
47
Q

What is acute lymphoblastic leukaemia (ALL)

A
  • Malignancy of lymphoid cells affecting either B or T lymphocytes cell lineage, arresting maturation and promoting uncontrolled proliferation of immature blast cells
48
Q

Who does acute lymphoblastic leukaemia (ALL) occur in

A
  • Most common childhood cancer

- Peak indigence 2-4 years

49
Q

What are the signs and symptoms of acute lymphoblastic leukaemia (ALL)

A

General

  • Lerthary
  • Bone pain
  • Anorexia

Marrow failure
- Neutropenia and resultant infection due to thrombocytopenia

Infiltration

  • hepatomegaly, splenomegaly, lymphadenopathy, testicular swelling
  • Thrombocytopenia and bleeding
  • Anaemia

CNS involvement
- Cranial nerve palsies and meningism

Lymphadenopathy
- Mediastinal – SVC obstruction

Abdominal Organomegaly
CNS involvement

50
Q

How do you diagnose Acute lymphoblastic leukaemia (ALL)

A
  • Abnormal full blood count – low haemophibic/high or low WCC/low platelets
  • Blast cells on blood film and bone marrow
  • Renal function
  • Blood film
  • Bone marrow biopsy
  • Immunophenotyping – CD34+, TdT
  • Cytogenetics
  • Mutations
51
Q

What is the treatment for Acute lymphoblastic leukaemia (ALL)

A
  • Remission induction – killed most of the cells – vincristine, prednisolone, daunorubicin, asparaginase
  • Consolidation – various combiantions of hcemotherapuetic agents
  • CNS directed therapy – high dose systemic and intrathecal methotrexate – drugs that penetrate the BBB
  • Maintenance therapy – vincristine, prednisolone, mercaptopurine and methotrexate for 2-3 years
52
Q

What is the response of treatment for Acute lymphoblastic leukaemia (ALL)

A

Childhood ALL

  • Greater than 95% achieve remission
  • Greater than 80% remain in remission
  • Treatment is now stratified on basis of initial presenting features and speed of response

Adult

  • Lower remission rate (80%) with long term remission of only 20-40%
  • May need allogenic bone marrow transplant
53
Q

What provides diagnostic and prognostic information in Acute lymphoblastic leukaemia (ALL)

A

ALL cytogenetics

- Provides important diagnostic and prognostic information

54
Q

Name the chronic leukaemias

A
  • Chronic myeloid leukaemia (CML)

- Chronic lymphocytic leukaemia (CLL)

55
Q

What is Chronic lymphocytic leukaemia (CLL)

A
  • Proliferation of small mature B lymphocytes in the BM and PB
56
Q

Who does Chronic lymphocytic leukaemia (CLL) present in

A
  • Median age of presentation is 65-70 years

- Incidence = 5-9/100,000

57
Q

What are the signs and symptoms of Chronic lymphocytic leukaemia (CLL)

A

Symptoms

  • Often none, presenting as surprise finding on routine FBC
  • Could have weight loss, night sweats, anorexia if severe

Signs

  • Enlarged rubbery non-tender nodes
  • Splenomegaly
  • Hepatomegaly
58
Q

How do you diagnose Chronic lymphocytic leukaemia (CLL)

A
  • FBC – lymphocytosis and anaemia
  • Blood film = Smudge cells (also known as smear cells)
  • Autoimmune haemolysis
  • Marrow infiltration = haemoglobin decreases, neutrophils decreased, platelets decreased
59
Q

In a white cell count what cell is raised in Chronic lymphocytic leukaemia (CLL)

A

Lymphocytes

60
Q

What does a blood film look like in Chronic lymphocytic leukaemia (CLL)

A
  • Lots of small mature lymphocytes with monomorphic appearance
  • Smear cells – artefact produced by smear
61
Q

What are the indications of treatment for Chronic lymphocytic leukaemia (CLL)

A
  • Some patients may just be observed initially

Indications for treamtnet

  • Progressive marrow failure
  • Massive LN/organomealgy
  • Systemic symptoms
  • Autoimmune cytopenias: haemolysis(AIHA), platelets (ITP)
62
Q

What is the treatment for Chronic lymphocytic leukaemia (CLL)

A
  • No benefit in treating early stage disease – can just be oberevd
  • Autoimmune complications (haemolytic anaemia) treated with steroids
  • Alkylating agents – chlorambucil – used less commonly as first line
  • Purine analogues – fludarabine
  • Combination chemotherapy – FCR
  • Rituximab is an anti- CD20 mAb – on surface of lots of B lymphocytes
  • Supportive care (immunisations/blood transfusions/treatment of infections)
63
Q

What are the poor prognostic features of Chronic lymphocytic leukaemia (CLL)

A
  • Lymphocytes doubling time = less than 12 months
  • Certain chromosomal changes
  • Mutations or deletions of the tumour suppressor gene TP53
64
Q

What does a bone marrow biopsy look like in Chronic lymphocytic leukaemia (CLL) and what does a blood film look like in CLL

A

Bone marrow Biopsy = full of CLL cells

Blood film = Smudge cells (also known as smear cells)

65
Q

do people get symptoms with Chronic lymphocytic leukaemia (CLL)

A
  • 80% of the patients diagnosed are asymptomatic – detected on routine FBC
66
Q

What is chronic myeloid leukaemia (CML)

A
  • Characterised by an uncontrolled clonal proliferation of myeloid cells
67
Q

What are the signs and symptoms of chronic myeloid leukaemia

A

Symptoms

  • Weight loss
  • Tiredness
  • Fever
  • Sweats
  • Gout – due to purine breakdown
  • Bleeding – platelet dysfunction
  • Abdominal discomfort – splenic enlargement

Signs

  • Splenomegaly
  • Hepatomegaly
  • Anaemia
  • Bruising
68
Q

What are the three phases of chronic myeloid leukaemia present (CML)

A
  • Chronic phase 3-5 years
  • Accelerated phase 3-6 months
  • Blast crisis – 3 months
  • Death
69
Q

What is the treatment of chronic myeloid leukaemia present (CML)

A
  • Imatinib (Glivec) - Tyrosine kinase inhibitor

- Novel small molecular inhibitor of bcr-abl; highly tumour specific

70
Q

What mutation causes chronic myeloid leukaemia present (CML)

A
  • discovery of t(9;22) (Philadelphia chromosome)
  • Nearly all cases involve this translocation of chromosomes 9 and 22
  • Called bcr-abl fusion gene
  • Overacting kinase
  • ABL protein is a tyrosine kinase (an enzyme that adds phosphate groups – phosphorylation)
  • After the fusion, oncoprotein has uncontrolled tyrosine kinase activity
71
Q

What is the name of the chromosome responsible for chronic myeloid leukaemia present (CML)

A

t(9;22) (Philadelphia chromosome)

72
Q

What is myelodysplasic syndrome

A
  • Ineffective production (or “dysplasia”) of blood cells.
  • Problem with hematopoietic stem cells in bone marrow so they end up making faulty (dysplastic) red cells, neutrophils and platelets (myeloid lineage)
73
Q

What are the symptoms of myelodysplasic syndrome

A

• Patients can develop severe anaemia, neutropenia and thrombocytopenia requiring blood transfusions. (bone marrow failure).

74
Q

Who does myelodysplasic syndrome usually effect

A

• Usually in elderly >65

75
Q

How do you diagnose myelodysplasic syndrome

A

• Diagnosis with blood film, bone marrow biopsy, cytogenetics.

76
Q

What is the prognosis of myelodysplasic syndrome

A

• Prognosis depends on type and severity.

77
Q

How do you treat myelodysplasic syndrome

A

• Supportive treatment-transfusions, treat infections, newer drugs-azacytadine (DNA demethylating agent) and bone marrow transplant.

78
Q

what disease can myelodysplasic syndrome transform to

A

• Can transform to AML

79
Q

What differentiates AML from ALL

A

AML - this has Auer rods present in it

80
Q

What are the complications of AML

A
  • Predisposition to infection
  • chemotherapy causes plaza rate levels to rise from tumour lysis so give allopurinol with chemotherapy and keep well hydrates with IV fluids
  • leukostasis may occur if there is a raised WCC count
81
Q

What are the types of acute lymphoblastic leukaemia

A
  • Common ALL – CD10 present (75%)
  • T cell ALL (20%)
  • B cell ALL (5%)
82
Q

What are the complications of CLL

A
  • Warm Autoimmune haemolysis
  • Increased infection due to hypogammaglobulinaemia – leading to recurrent infections
  • Marrow failure
  • Transformation to high grade lymphoma (Richter’s transformation)
83
Q

What is Richter’s transformation

A

This occurs when leukaemia cells enter the lymph node and change into high grade fast growing non-hodgkin’s lymphoma

84
Q

What are the indications that Richter’s transformation has taken place

A

Indicated by

  • Lymph node swelling
  • fever without infection
  • weight loss
  • night sweats
  • nausea
  • abdominal pain
85
Q

What do tests show in chronic myeloid leukaemia

A
  • Increase in granulocytes at different stages of maturation +/- thrombocytosis
  • Decreased leukocyte alkaline phosphatase
  • Increased neutrophils, monocytes, basophils, eosinophils
  • Reduced haemoglobin
  • Increased urate, Increase B12
  • Bone marrow hypercellular
86
Q

List the main differences between acute and chronic leukaemias

A

Acute

  • Acute onset
  • Happens within weeks
  • ALL = only in children
  • Come from the most immature cells
  • Bear no resemblance to the mature cells

Chronic

  • Years without any symptoms at all
  • Slow onset of disease
  • Resemble the mature cells a little bit more

Year 3 - Clinical Science and Professionalism (32 decks)

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