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Year 3 Clinical > Concepts in Malignant Haematology and Acute Leukaemia > Flashcards

Concepts in Malignant Haematology and Acute Leukaemia Flashcards

1
Q

Kinetics of normal haemopoiesis?

A
  1. Self-renewal - haemopoietic stem cells are capable of this
  2. Proliferation
  3. Differentiation or lineage commitment
  4. Maturation
  5. Apoptosis

NOTE - a normal bone marrow aspirate will reflect this, with different cell types, inc. mature cells

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2
Q

How can normal, more mature cells be identified?

A

Morphology:
• Blood count
• Blood film

Cell surface antigens,e.g: to recognise glycophorin A on red cells

Enzyme expression is a historic technique, e.g: myeloperoxidase on neutrophils

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3
Q

How can normal progenitor / stem cells be identified?

A

Cell surface antigens (using immunophenotyping), e.g: CD34

Cell culture assays

NOTE - cannot differentiate progenitors / stem cells from one another on the basis of morphology alone

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4
Q

Pathological characteristics of malignant haemopoiesis?

A

Increased numbers of abnormal and dysfunctional cells, with a loss of normal activity:
• Loss of haemopoiesis capabilities, e.g: acute leukaemias
• Loss of immune function, e.g: certain lymphomas

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5
Q

Why does malignant haemopoiesis occur?

A 
1 / more of the following:
• Increased proliferation
• Lack of differentiation
• Lack of maturation
• Lack of apoptosis
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6
Q

Classifications involving proliferation of abnormal progenitors?

A

Proliferation of abnormal progenitors with block in differentiation / maturation, e.g: acute myeloid leukaemia

Proliferation of abnormal progenitors with no block in differentiation / maturation, e.g: chronic myeloid leukaemia; mature cells are present but are abnormal and present in large quantities

ADD IMAGE

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7
Q

Causes of haematological malignancies?

A

Genetic, epigenetic and environmental interaction

Somatic mutations in regulatory genes:
• Driver mutations
• Passenger mutations

Recurrent cytogenetic abnormalities, e.g: deletions, chromosomal translocations, etc; not causal in most cases but contributory

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8
Q

Difference between driver mutations and passenger mutations?

A

Driver mutations - in genes that regulate growth; they confer a growth advantage on the cells and are selected during the evolution of the cancer

Passenger mutations (‘noise’) - in less important regions but push the cell towards cancer; do not confer a growth advantage but happened to be present in an ancestor of the cancer cells, when it acquired one of its drivers

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9
Q

Consequences of driver mutations?

A

Can select CLONES, which are populations of cells derived from a single parent cell; this parent cell has a genetic marker (driver mutation or chromosomal change) that is shared by the daughter cells

These clones can diversify but will still contain a similar genetic ‘backbone’

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10
Q

Difference between normal haemopoiesis and malignanct haemopoiesis?

A

Normal haemopoiesis - polyclonal

Malignant haemopoiesis - monoclonal

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11
Q

Evidence that haematological malignancies develop, at least partially, due to a genetic input?

A

Guthrie cards can be screened retrospectively in children who develop acute lymphoblastic leukaemia

With a pair of monozygotic twins, one twin has all and the other has detectable pre-leukaemic cells but does not develop disease

Somatic mutations observed in 10% of persons >65 years of age, without a blood disorder, can predict the risk of haem malignancy subsequently

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12
Q

Methods of classifying haematological malignancies?

A
  1. Based on lineage
  2. Based on developmental stage (precursor) within lineage
  3. Based on anatomical site involved
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13
Q

Types of haematological malignancies, with relation to lineage?

A

Myeloid

Lymphoid

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14
Q

Types of haematological malignancies, with relation to developmental stage (precursor) within lineage?

A

Acute lymphoblastic leukaemia (issue with progenitor cells)

Chronic lymphocytic leukaemia (issue with mature cells)

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15
Q

Types of haematological malignancies, with relation to anatomical site involved?

A

Blood involvement - leukaemia

Lymph node involvement - lymphoma

NOTE:
• Chronic lymphocytic leukaemia can inv. blood and lymph nodes
• Myeloma is a plasma cell malignancy in marrow

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16
Q

Differences between acute leukaemia & high-grade lymphomas, compared to chronic leukaemias & low-grade lymphomas?

A

Acute leukaemias and high-grade lymphomas are histologically, and usually clinically, more aggressive

17
Q

Histological features of aggression?

A

Large cells with high N : C ratio

Prominent nucleoli

Rapid proliferation

18
Q

Clinical features of aggression?

A

Rapid progression of symptoms

19
Q

Examples of haematological malignancies?

A

Acute myeloid leukaemia

Acute myeloblastic leukaemia

Chronic myeloid leukaemia

Chronic lymphocytic leukaemia

20
Q

What is acute leukaemia?

A

A rapidly progression clonal malignancy of the marrow or blood, with maturation defects(s)

Excess of ‘blasts’ (≥50%) in either the peripheral blood or bone marrow, due to block in differentiation & maturation

There is a decrease/loss of haemopoietic reserve

21
Q

2 types of acute leukaemia?

A

Acute myeloid leukaemia (AML) -

Acute lymphoblastic leukaemia (ALL) - malignant disease of primitive lymphoid cells, i.e: of lymphoblasts

22
Q

Occurrence of ALL?

A

Most common childhood cancer

23
Q

PC of ALL?

A

Due to marrow failure (pancytopaenia):
• Anaemia
• Infections
• Bleeding

Leukaemic effects:
• High count with obstruction of circulation
• Extramedullary inv. of areas outside the marrow and blood, e.g: CNS, testis

Bone pain

24
Q

Occurrence of AML?

A

More common in the elderly (>60 years of age)

May be ‘de novo’ or secondary

25
Q

PC of AML?

A

Can be similar to ALL (with marrow failure)

Various sub-groups of AML may have characteristic presentation, e.g:
• DIC (coagulation defect)
• Gum infiltration

26
Q

Ix for acute leukaemia?

A
  1. Blood count and film
  2. Coagulation screen
  3. Bone marrow aspirate:
    • Morphology - what do the cells look like?
    • Immunophenotype (flow-cytometry) - are there lineage-specific proteins on the cell surface?
    • Cytogenetics
    • Trephine - piece of bone that allow better assessment of cellularity; it is helpful when the marrow aspirate is sub-optimal
27
Q

Blood film results with acute leukaemia?

A

Reduction in normal

Presence of abnormal; this include abnormal blast cells with a high N : C ratio

28
Q

What are Auer rods?

A

Blood film characteristic of AML

EXAMS

29
Q

For a definitive diagnosis of AML or ALL, what is required?

A

Immunophenotyping is required

NOTE - even if cells from AML and ALL look alike. they express lineage-assoc. proteins; this differentiation is important, as AML and ALL have different treatments

30
Q

Curative treatment of acute leukaemia?

A

Multi-agent chemotherapy

31
Q

Curative treatment of ALL?

A 
Chemo can last up to 2-3 years; there are different phases of treatment, of varying intensity:
• Induction
• Consolidation
• Intensification
• Maintenance
32
Q

Curative treatment of AML?

A

Normally intensive treatment, with 2-4 cycle of chemotherapy (5-10 days of chemo followed by 2-4 weeks of recovery); there is prolonged hospitalisation

33
Q

What is a Hickman line?

A

Used to remove blood samples

OR

Deliver chemotherapy

34
Q

Issues assoc. with marrow suppression?

A
  1. Anaemia
  2. Neutropaenia:
    • Infections
  3. Thrombocytopaenia:
    • Bleeding - purpura and petechiae
35
Q

Particular infection concerns in neutropaenic patients?

A

Gram -ve bacteria can cause fulminant life-threatening sepsis

36
Q

Complications of treatment?

A

N&V, hair loss

Liver, renal dysfunction

Tumour lysis syndrome (during 1st course of treatment)

Infection:
• Bacterial - empirical treatment with broad-spectrum antibiotics if the patient has NEUTROPAENIC FEVER (important)
• Fungal - consider if prolonged neutropaenia and persisting fever unresponsive to anti-bacterial agents
• Protozoal, e.g: PJP (more relevant in ALL therapy)

Late effects, e.g:
• Infertility
• Cardiomyopathy with anthracyclines

37
Q

Outcomes of treatment?

A

May patients enter remission; may not be durable, depending on the type of acute leukaemia and many patients relapse

Some patients die of treatment-related toxicity

38
Q

Other treatment options?

A

Targeted treatments, e.g: molecular targeting with kinase inhibitors for ALL with the Philadelphia chromosome

Allogeneic stem cell transplantation in select patients

Year 3 Clinical (100 decks)

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