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CSP > Leukaemia > Flashcards

Leukaemia Flashcards

1
Q

The clinical features, laboratory diagnoses and treatment options for leukaemias

A

h

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2
Q

The classification of the four types of acute and chronic leukaemias.

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

What cells is blood made up of?

A

RBCs
WBCs
Platelets

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4
Q

Describe the basics of normal haematopoietic development.

A

stem cell

  • -> committed progenitors
  • -> mature (differentiated) cells
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5
Q

What are the two committed progenitor cell types?

A

Myeloid vs lymphoid

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6
Q

What do lymphoid progenitor cells become?

A

Naive B lymphocytes (–> plasma cells)

T lymphocytes

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7
Q

What do myeloid progenitor cells become?

A 
Neutrophils
Eosinophils
Basophils
Monocyte
Platelets
Red cells
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8
Q

What do myeloid progenitor cells become?

A 
Neutrophils
Eosinophils
Basophils
Monocyte
Platelets
Red cells
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9
Q

How haematological malignancies occur - what lineages do the following malignancies occur from?
ALL
AML
CLL

A

ALL - lymphoid progenitor cells
AML - myeloid progenitor
CLL - naive B lymphocytes

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10
Q

From what lineages do the following occur?
Lymphomas
Myeloma
Myeloproliferative disorders

A

T lymphocyte
Plasma cells
Neutrophils

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11
Q

From what lineages do the following occur?
Lymphomas
Myeloma
Myeloproliferative disorders

A

T lymphocyte
Plasma cells
Neutrophils, eosinophils, basophils, monocyte, platelets, red cells

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12
Q

Where do all the blood cells come from?

A

Bone marrow

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13
Q

What laboratory tools are there for diagnosing haematological malignancies?

A

Morphology – Blood film, Bone marrow biopsy
Immunophenotype – Flow cytometry
Genetic and molecular features – Chromosome abnormalities (G-banding and FISH), Gene point mutations, insertions/deletions (PCR-based)

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14
Q

Immunophenotyping - why is it useful?

A

Eg: blast and lymphocyte can look morphologically
similar even to trained eyes BUT immunologically diverse (different surface antigens).
It can help distinguish:
• Cancerous from normal tissue
• Different types of haematological malignancies

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15
Q

What is G banding used for?

How does it work?

A

Used to detect chromosomal abnormalities

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

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16
Q

What is monosomy 7 a feature of?

A

AML

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17
Q

What is translocation 15:17 a feature of?

A

APML

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18
Q

What is FISH?

A

Technique using fluorescent probes to detect a

specific DNA sequences

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19
Q

What is FISH used for?

A

Does not need to be used with cells in metaphase
Can identify chromosomal translocations or gains or
losses of regions in the genome

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20
Q

What is a mutation?

A

Change in the DNA sequence

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21
Q

When can a mutation contribute to disease/cancer?

A

If the change affects the protein sequence and function of the translated protein

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22
Q

A 23 year old teacher visits her GP complaining of tiredness and gum bleeding.
On examination she is pale, has swollen gums and lots of bruising and petechia.
Blood tests showed:
• Hb: 5g/dL (low)
• WCC 150 (high)
• Plt 6 (low)
Given intensive chemotherapy but died due to overwhelming neutropenic sepsis.
What is the diagnosis?

A

AML

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23
Q

Acute leukaemias: AML and ALL

What are these characterised by?

A

Accumulation of large numbers of undifferentiated cells called ‘BLASTS ‘ in bone marrow, due to a block in differentiation. These blasts rapidly overwhelm normal blood cells and then spill into the peripheral blood.

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24
Q

How is AML and ALL diagnosed?

A

Diagnoses requires > 20% blasts in bone marrow or blood

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25
Q

Signs and symptoms of AML and ALL.

A

Low Hb - anaemia, tiredness, shortness of breath
WCC - infections if low or leucostasis (high white cell count making the blood viscous causing problems with blood flow in vessels leading to stroke/confusion/SOB) if high.
Low platelets - bleeding and bruising

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26
Q

Explain the signs and symptoms of AML/ALL.

A

They are signs and symptoms of bone marrow failure

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27
Q

How is AML/ALL treated?

A

Require intensive, high dose, myelosuppressive chemotherapy.

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28
Q

Prognosis of AML/ALL.

A

Aggressive/fast growing/fatal if untreated.

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29
Q

What age group is AML increasingly frequent in?

A

Older people (most common in 80-84 year olds)

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30
Q

Define Acute Myeloid Leukaemia.

A

Malignant transformation of a myeloid precursor cell usually at a very early stage of myeloid development.

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31
Q

How does AML present?

A

Bone marrow failure:
- neutropenia: fever, pneumonia, fungal infection
- thrombocytopenia: bleeding (GI, cerebral)
- anaemia
• Elevated white blood cell count (blasts from bone marrow spilling into peripheral blood):
- leukostasis (headache, stroke, confusion)
- gum infiltration/skin infiltration
• Bone Pain

32
Q

How is AML diagnosed?

A
  • Abnormal full blood count (low Hb/high or low WCC/low plts)
  • Renal function
  • Raised urate and LDH - sign of rapid cell turnover
  • Clotting (APML)
  • Blood film - auer rods
  • Bone marrow biopsy
  • Immunophenotyping (CD34+)
  • Cytogenetics:-7q
  • Mutations: FLT3
33
Q

When are auer rods seen/what are they?

A 
AML 
Elongated structures (grouping of granules)
34
Q

What is Acute Promyelocytic Leaukaemia?

What is the characteristic morphology of cells?

A

A subtype of AML

Hypergranular promyelocytes

35
Q

What translocation is associated with APML? What does it lead to?

A

t15:17

Fusion of PML and RARA to generate PML-RARA oncoprotein

36
Q

How does APML present?

A

Abnormal clotting - severe bleeding or clots.

37
Q

How is APML treated? What is the prognosis?

A

ATRA/Arsenic/anthracyclines

Very treatable - complete remission rates of >90%.

38
Q

Supportive treatment of AML.

A

Blood and platelet transfusion

Prophylactic antibiotics and prompt treatment of
neutropenic sepsis (Temp >38, neutrophils <1) with broad spectrum antibiotics e.g meropenem.

Emergency venesection or leucopharesis if leucostasis

Fluids, allopurinol/rasburicase if tumour lysis

39
Q

How does tumour lysis present?

A

renal failure, high K+, high urate, high phosphate, low calcium

40
Q

In AML, patients are risk stratified based on…?

How does this affect treatment?

A

cytogenetics and mutations

Good risk –> 4 cycles of intensive chemo
Intermediate/poor risk –> chemotherapy to remission then allogeneic transplant

41
Q

What chemotherapy drugs are used in AML and how to they work?

A

Usually a combination of daunorubicin and cytarabine (anti-metabolites – interfere with DNA synthesis)

42
Q

Chemotherapy affects cells that have a high turnover, such as leukaemia cells. What normal cells does it affect? (3)

A

Hair cells, cells of the gut and intestinal tract, and bone marrow

43
Q

Allogenic transplant - what is the difference between myeloablative and reduce intensity?

A

Myeloablative wipes out BM completely, reduced intensity makes some room in BM for new stem cells. Myeloablative is used in younger patients as it is very intensive and has lots of side effects and these patients can tolerate it better.

44
Q

How does allogenic transplant work?

A

Via immune reaction against residual tumour cells (though conditioning chemoradiotherapy can help kill AML cells). The immune effect is called graft-versus-leukaemia effect.

45
Q

How is a bone marrow transplant done?

A

G-CSF given to donor (or patient) subcut for 4 days (this is to mobilise CD34+ stem cells into peripheral blood)
Bone marrow harvested on day 5 from iliac crests of donor
Collected by leucapheresis
Marrow filtered in op room
Filtered marrow is given to recipient

46
Q

Prognosis of AML (compare children to elderly).

A

Depends on risk group.
50% of children and young adults can expect long term cure.
Less than 10% of patients over 70 can expect a long term remission.

47
Q

What is the commonest childhood cancer?

A

Acute Lymphoblastic Leukaemia

48
Q

What is ALL?

A

malignant disease of undifferentiated lymphoblasts

49
Q

What is the peak incidence of ALL?

A

2-4 yrs

50
Q

Symptoms and Signs of ALL.

A 
– Lethargy; bone pain; anorexia
 • Marrow failure
– Neutropenia and resultant infection
– Thrombocytopenia and bleeding
– Anaemia
• Lymphadenopathy (particularly T-ALL)
– Mediastinal : SVC obstruction
• Abdominal organomegaly
• CNS involvement (5%)
51
Q

ALL diagnosis.

A
  • Abnormal full blood count (low Hb/high or low WCC/low plts)
  • Renal function/LFTs
  • Blood film
  • Bone marrow biopsy
  • Immunophenotyping (CD34+, TdT)
  • Cytogenetics
  • Mutations
52
Q

What cytogenetics are associated with ALL.

A

Hyperdiploidy common – high hyperdiploid favourable (51-65 chromosomes)
t(9;22) (Philadelphia) and t(4;11) both adverse prognostically

53
Q

ALL treatment is divided into four phases. What are these?

A

Remission induction - vincristine, prednisolone, daunorubicin, asparaginase.

Consolidation - various combinations of chemotherapeutic agents.

CNS directed therapy - high dose systemic and intrathecal methotrexate.

Maintenance therapy - vincristine, prednisolone,
mercaptopurine and methotrexate for 2-3 years

54
Q

Prognosis of ALL in childhood.

A

> 95% achieve remission

>80% will remain in remission

55
Q

Prognosis of ALL in adulthood.

A

Lower remission rate (80%) with long term remission of

only ~20-40%. Many need allogeneic bone marrow transplant.

56
Q

How do chronic leukaemias differ from acute?

A

Slower growing

Don’t always require immediate treatment

57
Q

What is Chronic Lymphocytic Leukaemia?

A

Proliferation of small mature B lymphocytes in the bone marrow and peripheral blood

58
Q

What is the incidence of Chronic Lymphocytic Leukaemia?

A

5-9 /100,000

59
Q

What is the median age of presentation of Chronic Lymphocytic Leukaemia patients?

A

65-70yrs

60
Q

What is the usual presentation of CLL?

A

80% of the patients diagnosed are asymptomatic – detected on routine FBC.

61
Q

What are the signs/symptoms of CLL?

A
  • Tiredness, night sweats, weight loss
  • Symptoms related to anaemia
  • Thrombocytopenia, lymphadenopathy
  • Hepatosplenomegaly
  • Recurrent infections due to immunosuppression (hypogammaglobulinaemia)
62
Q

How is CLL diagnosed?

A

• Lymphocytosis > 5
• Normochromic normocytic anaemia +/- autoimmune
haemolytic anaemia
• Thrombocytopenia
• Hypogammaglobulinaemia
• Mature lymphocytosis with smear cells on blood film
• Diagnosis made by immunophenotyping and characteristic blood film
• On patients with a raised FBC-Look at differential.

63
Q

What is seen on the blood film in CLL?

A
  • Lots of small mature lymphocytes with monomorphic appearance
  • Smear cells – artefact produced by smear
64
Q

Three Binet stages of CLL - which require treatment?

A

B and C (not A)

65
Q

Some patients with CLL may just be observed initially. Name some indications for treatment.

A
  • Progressive marrow failure
  • Massive LN/organomegaly
  • Systemic symptoms
  • Autoimmune cytopenias : haemolysis (AIHA), platelets (ITP)
66
Q

Treatment for CLL.

A

• Steroids (for autoimmune complications)
• Alkylating agents- chlorambucil
• Purine analogues- Fludarabine
• Combination Chemotherapy-FCR (fludarabine,
cyclophosphamide, rituximab = anti-CD 20 mAb)
• Supportive care (immunisations, blood transfusions, treatment of infections)

67
Q

What is chronic myeloid leukaemia?

A

Disease of the stem cells in bone marrow

68
Q

What is seen on blood film in CML?

A

Increased granulocytes - all stages of maturation, often plenty of eosinophils (pink-orange granules) and basophils (thick granules)

69
Q

How does CML present?

A
  • Weight loss, tiredness, night sweats
  • Splenomegaly
  • Anaemia
70
Q

There are three stages of CML. What are they and how long do they last?

A

Chronic phase - 3-5 years
Accelerated phase - 3-6 months
Blast crisis - 3 months

71
Q

What is translocation 9:22 (Philadelphia chromosome) associated with?

A

CML

This translocation –> bcr-abl fusion gene –> uncontrolled tyrosine kinase activity

72
Q

How is CML treated?

A

Imatinib (Glivec)

Novel small molecule inhibitor of bcr-abl: highly tumour specific

73
Q

What is myelodysplastic 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).
It usually occurs in the elderly (>65).

74
Q

What are the complications of MDS?

A

Patients can develop severe anaemia, neutropenia and thrombocytopenia requiring blood transfusions. (bone marrow failure). It can transform to AML.

75
Q

How is MDS diagnosed and treated?

A

Diagnosis with blood film, bone marrow biopsy, cytogenetics.
Supportive treatment - transfusions, treat infections, newer drugs-azacytadine (DNA demethylating agent) and bone marrow transplant.

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