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CP reviewer 1 > Acute Leukaemia and MDS > Flashcards

Acute Leukaemia and MDS Flashcards

1
Q

What is acute leukaemia?

A

Result of accumulation of early myeloid (AML) or lymphoid (ALL) precursors in the bone marrow and other tissues

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2
Q

What are the 2 route of pathogenesis of acute leukaemia?

A
  1. Probably occurs by somatic mutation in a single cell within a population of early progenitor cells
  2. May arise de novo or secondary to prior chemotherapy/radiotherapy (prognosis worse) or another haematological condition
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3
Q

What is the median age of presentation of AML?

A
  • Median age: 69 years

* Incidence is increasing (ageing population)

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4
Q

What is the survival rate of AML?

A

Poor survival rate compared to those <60 years old (likely due to comorbidities)

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5
Q

What is the clinical presentation of AML?

A

o Features of bone marrow failure: anaemia (pale, tired), prone to infections (temperature, chest infection), easy bruising (low platelet count) and haemorrhage

o Organ infiltration by leukaemia cells may occur e.g. spleen, liver, meninges, testes and skin

o Gum hypertrophy

o Bleeding

o Anaemia

o Neutropenic sepsis

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6
Q

What are the haemological features of AML?

A

o Anaemia
o Low or high WCC with circulating leukaemia cells
o Low platelets

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7
Q

What is cytogenetics?

A

Cytogenetics is the branch of genetics that studies the structure of DNA within the cell nucleus (number and morphology of chromosomes)

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8
Q

How can AML be diagnosed?

A

o Morphology
o Immunological markers
o Cytogenetics (chromosomes): certain abnormalities correlate with prognosis e.g. t(8;21) inv(16) and t(15:17)

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9
Q

What are important prognostic factors in AML?

A

o Age (co-morbidities, more mutations driving leukaemia, poorer immune system)

o Chromosome abnormalities (good risk ones vs bad risk ones)

o Molecular features – NPM1 (good prognosis with chemotherapy) and FLT3-ITD (tend to have bad prognosis), present on cell surface

o Extramedullary disease (worse prognosis e.g. cutaneous leukaemia, CNS disease)

o Disease that doesn’t respond to treatment (refractory disease, worse prognosis)

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10
Q

Treatment for AML?

A

Intensive chemotherapy - all AML patients up to 80 years old should be considered for intensive treatment.

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11
Q

Describe the intensive chemotherapy given in AML

A

3-4 cycles of IV cytotoxic drugs given centrally (for each treatment, patient in hospital for around 4-6 weeks)

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12
Q

What are the risks associated with intensive chemotherapy?

A 
o	Death
o	Sepsis
o	Alopecia
o	Infertility
o	Tumour lysis Can also cause gout. 
o	Taste is metallic
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13
Q

What is tumour lysis?

A

A group of metabolic abnormalities that can occur during the treatment of cancer, where large amounts of tumour cells are killed off (lysed) at the same time by the treatment, releasing their contents into the bloodstream.

Waste products such as uric acid from tumour cells can plug up kidneys and cause problems. Can also cause gout.

IV treatment can relieve these symptoms.

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14
Q

What % of AML patients can be in complete remission after one cycle of intensive chemotherapy?

A

80-85%

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15
Q

What is the treatment for high risk AML patients (e.g. not responding to chemo, have the FLT3-ITD markers)?

A

Chemo + bone marrow transplant

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16
Q

Which patients require immediate intensive therapy for AML?

A

Critically ill patients with rapidly progressive disease (such as WCC >100 x 109/L) with respiratory / neurological / other organ compromise

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17
Q

For patients with AML but a lower white count, therapy can be put on hold for a couple of days.

What needs to be done in these couple of days?

A

No proven benefit to early initiation of treatment, wait for cytogenetics and mutational status prior to deciding on definitive therapy.

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18
Q

What are the complications of intensive therapy for AML?

A 
o	Alopecia
o	Nausea and vomiting
o	Potential loss of fertility 
o	Bruising/bleeding
o	Fatigue
o	Weight loss
o	Altered taste sensation
o	Infection 
o	Mortality
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19
Q

Why is the survival rate of AML so poor?

A
  • Age: hard to survive chemotherapy, especially with co-morbidities
  • High proportion of unfavourable cytogenetics
  • Frequent involvement of more immature leukaemia precursor clone
  • Multi-drug resistance (MDR1/P-glycoprotein)
  • Antecedent haem disorders
  • Higher levels of co-morbidity
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20
Q

AML is an aggressive disease. How soon after finishing intensive chemo does it tend to relapse? When is it likely cured?

A

o Typically relapses within 18 months of intensive chemotherapy

o At 4 years post chemo, likely cured

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21
Q

What is Cytarabine? Used to treat?

A

A chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin’s lymphoma.

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22
Q

Who would Cytarabine be useful for? Who is it not useful for?

A

o Widely used
o Useful in those not suitable for intensive chemotherapy

o Not good for patients with adverse cytogenetics
o Can cause side effects which may decrease quality of life without prolonging survival for that long

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23
Q

Why are hypomethylating agents?

A

Drugs that inhibits DNA methylation –> can alter proliferation of leukaemia cells. Used in AML.

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24
Q

Benefits of hypomethylating agents?

A

Well tolerated by ‘unfit’ elderly patients

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25
Q

2 examples of hypomethlyating agents?

A

Decitibine (dec) and azacytidine (aza)

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26
Q

What are 2 examples of chemo drugs used in low intensive therapy in AML?

A
  1. low dose Cytarabine

2. hypomethylating agents

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27
Q

What is Venetoclax? Mechanism?

A

A form of targeted therapy instead of chemotherapy (used in AML).

Restores apoptosis of cancer cells through BCL-2 inhibition (cancer cells die).

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28
Q

What would Venetoclax be used in combination with?

A

Azacytidine or low dose Cytarabine (increases survival)

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29
Q

What 2 proteins present on cell surfaces can be molecular markers of AML?

A
  1. FLT3-ITD (tend to have bad prognosis)

2. NPM1 (tend to have good prognosis with chemo)

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30
Q

Is the FLT3-ITD marker in AML a sign of good or poor prognosis?

A

Poor

31
Q

Is the NPM1 marker in AML a sign of good or poor prognosis?

A

Good (with chemo)

32
Q

FLT3 mutations occur in approx what % of AML patients?

A

30%

33
Q

What does the FLT3 mutation result in?

A

Constitutive activation of the FLT3 receptor –> The FLT3 gene encodes a tyrosine kinase receptor that plays a key role in controlling survival, proliferation and differentiation of hematopoietic cells.

34
Q

What is the function of the FLT3 gene?

A

The FLT3 gene encodes a tyrosine kinase receptor that plays a key role in controlling survival, proliferation and differentiation of haematopoietic cells.

35
Q

Some AML drugs act as FLT3 inhibitors (targeted treatment). What are 2 examples of these? What are they used to treat?

A

Used in AML treatment.

  1. Midostaurin
  2. Gilteritinib
36
Q

When would Venetoclax and Azacytidine be used in combination?

A

In non-intensive chemo (e.g. if patient cannot withstand intensive chemo)

37
Q

What are the 2 main common complications of AML and ALL?

A
  1. Neutropenic sepsis

2. Bleeding

38
Q

What is neutropenic sepsis?

A

Neutropenic sepsis is overwhelming infection that can affect people who have neutropenia.

Neutropenic sepsis is a potentially fatal complication of anticancer treatment (particularly chemotherapy - will cause neutrophil level to drop to 0).

39
Q

What causes bleeding in AML patients?

A

Low platelet count

40
Q

If a patient on chemo starts to exhibit a temperature, what is done immediately?

A

Given broad spectrum antibiotics

41
Q

What is the difference between AML and ALL?

A

AML and ALL are the two main types of acute leukaemia. The difference between them is the type of white blood cell affected.

AML: develops from myeloid cells (e.g. neutrophils, basophils, erythrocytes)

ALL: can develop from different types of lymphocytes (e.g. B cells or T cells)

42
Q

What does ALL stand for?

A

Acute lymphoblastic leukaemia

43
Q

Clinical presentation of ALL?

A
  • Fatigue
  • Bruising/bleeding
  • Weight loss
  • Night sweats
  • Hepatosplenomegaly
  • Lymphadenopathy
  • Mediastinal mass
44
Q

What is the commonest type of cancer in children?

A

ALL

45
Q

Prognosis of ALL?

A

o Childhood: 90-98% survival

o Less good in older age

46
Q

There are 4 components of chemo treatment for ALL patients? What are these?

A
  1. Induction (8 weeks)
  2. Intensificaction/CNS prophylaxis (4 weeks)
  3. Consolidation (20 weeks)
  4. Maintenance (2 years)
47
Q

Why do patients with ALL typically have to receive intrathecal chemotherapy?

A

ALL patients are much likely to have disease affecting the nervous system but drugs do not cross the blood brain barrier .

Therefore, have to give intrathecal chemo.

48
Q

What is intrathecal administration?

A

A route of administration for drugs via an injection (lumbar puncture) into the spinal canal, or into the subarachnoid space so that it reaches the CSF

49
Q

Which is one of the only chemo drugs that can cross the blood brain barrier?

A

Methotrexate

50
Q

As well as intrathecal chemo, what other drug would ALL patients receive if the disease has affected the nervous system?

A

Methotrexate - has some BBB permeability

51
Q

If the ALL patient is high risk, what would occur after the ‘intensification’ phase?

A

Bone marrow transplant

52
Q

What is the purpose of the ‘maintenance’ phase during ALL treatment?

A

Prevent relapse

53
Q

Describe each of the 4 phases of ALL chemo treatment

A
  1. Induction; ideally should be in remission after, or may need to change treatment or do BMT
  2. Intensification/CNS prophylaxis; chemotherapy is given directly into CSF via lumbar puncture
  3. Consolidation; 20 weeks
  4. Maintenance (2 years); 2 oral drugs and vincristine injection every 3 months, intra-thecal injection? – reduces mortality by 20%
54
Q

When does ALL relapse tend to occur? What is the average survival of relapse?

A

o Tends to occur within 18 months of stopping maintenance

o Average duration of survival at relapse is 4 months

55
Q

What are the 5 options for relapsed ALL?

A
  1. Further intensive chemo
  2. Blinatumomab
  3. Inotuzumad
  4. CAR-T cells
  5. BMT – sib/MUD/Cord/Haplo
56
Q

What is Blinatumomab? What is it used to treat? Mechanism?

A

Used to treat ALL.

2 antibodies stuck together;

1) CD3 antibody which sticks to T cells (what our immune system uses to kill cancer cells)
2) CD19 antibody (present on all B cells)

The vast majority of ALL are B cells. Giving Blinatumomab to people with B cell ALL brings the T cell in direct contact with the tumour cell, allowing it to be killed (cell lysis).

57
Q

What 2 drugs are currently used in treatment of relapsed ALL?

A
  1. Blinatumomab

2. Inotuzumad

58
Q

Is Blinatumomab a chemo drug?

A

No - is an antibody treatment

59
Q

Advs/disadvs of Blinatumomab?

A
  • Gives better survival and less side effects (no hair loss, infertility)
  • However, nervous system can be affected such as seizures, confusion
60
Q

What is Inotuzumad? What is it used to treat? Mechanism?

A

Used to treat ALL.

Is an antibody which sticks to CD22 (on surface of ALL). This antibody has a chemo drug attached to it.

When Inotuzumad binds to surface of leukaemia cells, the antibody AND the chemo drug is taken into the cell –> is a way of delivering chemo directly into cancer cells to kill them from within.

61
Q

What is the target of Inotuzumad?

A

CD22 receptor (predominantly restricted to B cells)

62
Q

What is the target of Blinatumomab?

A

1) CD3 antibody sticks to T cells

2) CD19 antibody (present on all B cells)

63
Q

What is CAR-T cell therapy?

A

CAR T-cell therapy is a type of immunotherapy used in ALL.

64
Q

Mechanism of CAR-T cell therapy?

A

Modifying patient’s own T cells so they directly target the leukaemia cells and reinfusing them into people.

65
Q

Side effects of CAR-T cell therapy?

A

As CAR T cells multiply, they cause massive amounts of chemicals called cytokines to be released into the blood.

Side effects can include; very high fevers and dangerously low blood pressure in the days after treatment is given

66
Q

How is neutropenic sepsis treated

A

fever, hypotension, organ impairment

67
Q

Symptoms of neutropenic sepsis?

A

Treat with broad spectrum IV antibiotics as soon as suspected

68
Q

What is myelodysplasia (MDS)?

A
  • Represents several related disorders with common features
  • Bone marrow failure syndrome that results in ineffective haematopoiesis with reduced production of one or more of the peripheral blood cell images
69
Q

Features of MDS?

A
  • Dysplasia e.g. multi-nucleated cells
  • Inefficient haematopoiesis
  • Cytopenias (blood cells are made by are abnormal so are not pushed out to the blood stream)
  • Increased risk of transformation to AML
70
Q

What is there an increased risk of MDS transforming into?

A

AML - Used to be called ‘pre-leukaemia’

71
Q

What is the IPSS-R score?

A

Scoring System for Myelodysplastic Syndromes (Risk Assessment Calculator)

High score = higher risk and worse prognosis

72
Q

Treatment for low risk MDS?

A
  • May only need to monitor patient
  • Only treat if symptomatic
  • Erythropoietin for anaemia
  • Blood product support as necessary (transfusion)
73
Q

Treatment for high risk MDS?

A
  • Treatment aimed at altering natural history of the disease
  • If fit enough treat as per AML with intensive chemotherapy and bone marrow transplant
  • If not fit or complex cytogenetics consider azacytidine (low intensity chemo drug)
74
Q

Symptoms of MDS?

A

Fatigue
Infection
Bleeding

CP reviewer 1 (59 decks)

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