Leukaemias Flashcards

1
Q

What are the 2 main classes of leukaemia?

A

Acute leukaemia
Chronic leukaemia

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2
Q

What is an acute leukaemia?

A

A rapidly progressive, clonal malignancy of the marrow/blood in which there is a block preventing maturation of precursor cells

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3
Q

How is acute leukaemia clinically defined?

A

Acute leukaemia is defined as an excess of blasts ≥20% in either the peripheral blood or bone marrow

This can cause a decrease or loss of normal haemopoietic reserves, leading to anaemia or thrombocytopenia

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4
Q

What are the 2 main types of acute leukaemia?

A

Acute myeloid leukaemia (AML)
Acute lymphoblastic leukaemia (ALL)

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5
Q

What is acute myeloid leukaemia (AML)?

A

This is a leukaemia affecting the primitive myeloid cells, resulting in a build up of excess myeloblasts

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6
Q

What age is AML most common in?

A

Those over 60

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7
Q

What are some clinical features of AML and ALL?

A

Marrow failure
Leukaemic effects (Intra- or extra-medullary)

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8
Q

What are some symptoms of marrow failure in AML and ALL?

A

Anaemia
Infection
Bleeding

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9
Q

What is meant by leukaemic effects?

A

Those caused by a high precursor count, casing obstruction to circulation

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10
Q

What are some common sites of extra-medullary leukaemic effects in AML and ALL?

A

CNS
Skin
Testes
Periosteum (Causes bone pain)

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11
Q

What are some supportive management options used in AML and ALL?

A

Blood products
Antibiotics

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12
Q

What is 1st line management of AML in those who can tolerate it?

A

Intensive chemotherapy (3-4 cycles) can be used, requiring prolonged hospitalisation (6 weeks)

This chemotherapy is often given via Hickman-line which passes straight into the superior vena cava

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13
Q

What alternative treatments are used in AML treatment?

A

Less intensive chemotherapy
Allogenic stem cell transplantation

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14
Q

What is acute lymphoblastic leukaemia (ALL)?

A

Acute lymphoblastic leukaemia is a leukaemia affecting the primitive compartment of the lymphoid lineage

It is the lymphoid counterpart of AML

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15
Q

What is the most common childhood cancer?

A

ALL

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16
Q

What is ALL classified as if t speaks to the lymph nodes?

A

Lymphoblastic lymphoma

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17
Q

What is the 1st line treatment of ALL?

A

Intense chemotherapy can be given to those who can tolerate it

This chemotherapy is often given via Hickman-line which passes straight into the superior vena cava

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18
Q

What are some targeted treatment options available in some genetic subsets of ALL?

A

CNS-directed chemotherapy
Immunotherapy
CAR-T
Allogenic stem cell transplant

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19
Q

Why is CNS-directed chemotherapy used?

A

Normal chemotherapy cannot cross the blood-brain barrier, and so any cancer affecting the CNS may require direct treatment

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20
Q

What are the current 2 immunotherapeutic drugs against ALL?

A

Blinatumomab
Inotuzomab

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21
Q

How does blinatumomab work?

A

Blinatumomab is a bi-specific’ antibody created against an antigen expressed on leukaemic cells and against T cells via binding to CD3

This mediates the reaction between the leukaemic cell and T cell, causing cell lysis

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22
Q

How does inotuzomab work?

A

Inotuzomab is an antibody against an antigen on leukaemic cells which with conjugated to a cytotoxic drug, therefore directly delivering the drug to the cells

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23
Q

How does CAR-T therapy work?

A

CART (Chimaeric antigen receptor T-cell) therapy is also a possible treatment option, in which lymphocytes are genetically modified to recognise and be activated by antigens expressed on leukaemic cells

24
Q

What is a common subtype of AML?

A

Acute promyelocytic leukaemia (APL)

25
What is APL?
This is a sub-type of AML, with a specific chromosomal translocation t(15;17), which is associated with DIC
26
What is the current treatment for APL in cases of timely diagnosis?
Combination therapy of all-trans retinoic acid (ATRA) with arsenic trioxide as ATRA switches off DIC effectively
27
What are some investigations required in acute leukaemia?
- Morphology - Coagulation screen - DIC - Bone marrow aspirate - Immunophenotyping by flow cytometry (Required for definitive diagnosis) - Cytogenetics and molecular genetics - Trephine (Piece of bone) enables better assessment of cellularity and helpful when liquid aspirate is unsuccessful
28
What will morphology show in acute leukaemia?
Reduction in red cells Presence of abnormal cells: - Blasts with a high nuclear:cytoplasmic ratio - Open chromatin - Nucleolus - Auer rods (Suggestive of myeloid))
29
What are some complications of marrow suppression in chemotherapy?
- Anaemia - Neutropenia - Infections - Thrombocytopenia
30
What is the risk of gram -ve bacterial infection in chemotherapy patients?
Risk of life-threatening neutropenic sepsis within a few hours
31
What are some side-effects of anti-leukaemic treatment?
- Nausea and vomiting - Hair loss - Liver, renal dysfunction - Tumour lysis syndrome (Breakdown of tumour in response to treatment can harm the patients) - Infection
32
What is the prognosis of childhood ALL?
>85-95% cure rate
33
What is the prognosis of adult ALL?
30-40%
34
What is the prognosis of adult AML in those under 60?
40-50% (>95% in some sub-types)
35
What is the prognosis of adult AML in those over 60?
≤10%
36
What are the 2 main types of chronic leukaemia?
Chronic lymphocytic leukaemia (CLL) Chronic myeloid leukaemia (CML)
37
What is CLL?
This is a chronic leukaemia affecting the less-primitive compartment of the lymphoid lineage
38
What is the median age of diagnosis of CLL?
72
39
How does CLL affect the body?
Abnormal proliferation of lymphocytes causes crowding of the bone marrow, blood, lymph nodes, liver and spleen
40
What are some symptoms of CLL?
- Often asymptomatic - Night sweats - Fever - Fatigue - Weight loss - Lymphadenopathy - Splenomegaly - Hepatomegaly - Cytopenia - Infection
41
What are some possible complications of CLL?
Evan's syndrome Richter's transformation Warm (IgG) autoimmune haemolysis
42
What is Evan's syndrome?
Autoimmune cytopenia - A syndrome of both autoimmune haemolysis and autoimmune thrombocytopenia purpura
43
What is Richter's transformation?
This is the transformation of CLL into a different, often high grade lymphoma, occurring in between 2 and 10% of patients
44
How is CLL diagnosed?
- Morphology - Immunophenotyping - Genetic testing (Including TP53 mutations) - Immunoglobulin levels - Direct antibody testing (DAT) - CT (Chest, abdomen, pelvis)
45
What will morphology show in CLL?
Morphology will show high presence of lymphocytes and a number of smear cells (Unique) Smear cells are cells in which an abnormal membrane leads to cell “splattering”
46
What is the purpose of treatment in CLL?
This is considered incurable in most patients but there is good disease control with modern therapy, therefore preventing progression Most patients die with it, not because of it
47
What is the treatment strategy in asymptomatic CLL?
In cases of asymptomatic CLL, then no treatment is required as the disease will often not progress (Often cases in which patients claim they are curing their leukaemia with herbal remedies or CBD is just a case of asymptomatic CLL)
48
What is the treatment strategy of symptomatic CLL?
Anti-leukaemic treatment is used, but with poor prognosis
49
What is chronic myeloid leukaemia?
This is a chronic leukaemia, affecting the primitive compartment of the myeloid lineage
50
What causes CML?
A mutation in the Philadelphia chromosome (BCR-ABL1 re-arrangement)
51
What are the effects of CML on the body?
It is chronic, so there will be excessive proliferation with maturation, causing excessive production of granulocytes and precursors (myelocytes), resulting in neutrophilia, eosinophilia and basophilia
52
What is a possible complication of CML?
This can undergo blast transformation, most commonly after 3-5 years, when it resembles acute leukaemia and maturation is stopped, leading to an increase in precursor cells in the bone marrow
53
What are some possible symptoms of CML?
- Gout - Fatigue - Weight loss - Sweats - Splenomegaly - Marrow failure - Thrombosis
54
What are some blood count changes that will occur in CML?
- Normal or reduced Hb - Leucocytosis with neutrophilia, myeloid precursors (Myelocytes), eosinophilia and basophilia - Thrombocytosis
55
What is the management option for CML?
Durable disease responses with tyrosine kinase inhibitors (eg Imatinib) – used to be continuous treatment, but now able to stop in some, without disease recurrence This can greatly increase life expectancy to normal, as it kills cells with this mutation and therefore gets rid of Philadelphia genes CML is the paradigm for targeted therapies in oncology
56