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Cancer Pharmacology > Haematological Malignancies (1) > Flashcards

Haematological Malignancies (1) Flashcards

1
Q

What is patient stratification?

A

Separate people into groups based on their genetic mutations and therefore the ability for a cancer cell to be treated with certain therapies

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2
Q

What cells does the lymphoid compartment make?

A

T cells
B cells
NK cells

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3
Q

Give examples of cells which go down the myeloid compartment

A

Red cells
Neutrophils
Platelets

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4
Q

Name the main types of haematological cancers

A 
Chronic myeloid leukaemia 
Chronic myeloproliferative disorders 
Acute myeloid leukaemia 
Acute lymphoblastic leukaemia 
Lymphomas 
Chronic lymphocytic leukaemia 
Myeloma
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5
Q

Where does acute myeloid leukaemia occur?

A

In the primitive cells

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6
Q

Where does acute lymphoblastic leukaemia occur?

A

In the primitive cells of the lymphoid lineage

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7
Q

Where does myeloma occur?

A

In plasma cells

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8
Q

What is the most aggressive form of cancer in humans?

A

Burkitt lymphoma

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9
Q

What is the doubling time of Burkitt lymphoma?

A

Less than 24 hours

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10
Q

How many cases of Burkitt lymphoma can be cured?

A

90%

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11
Q

What percentage of child patients can be cured from acute lymphoblastic leukaemia?

A

90%

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12
Q

What percentage of young patients can be cured from Hodgkins lymphoma?

A

90%

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13
Q

What is the survival time for patients with multiple myeloma?

A

10 years with a good quality of life

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14
Q

What percentage of people are cured from acute myeloid leukaemia?

A

97% in some forms

10% in other forms

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15
Q

What side effects can occur in response to haematological treatments?

A 
Blood blisters 
Damage to mouse lining 
Reduced bone marrow cells 
Skin infections 
Infections such as in the lung 
Heart damage - can cause cardiomyothapy 
Hair loss 
Diarrhea 
Vomiting
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16
Q

When do you typically respond well to chemotherapy is you have ALL?

A

If you are over the age of 1 but under 10

If your white cell count was less than 50

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17
Q

What are the 3 components of risk stratification?

A

Reduce the toxicity of treatment for those who don’t need it
Increase intensity in those who do
Useful to identify early on during treatment

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18
Q

What is the NCI risk criteria based on?

A

Age and white cell count at presentation
Cytogenetics
Microscopic speed of clearance of leukaemic cells

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19
Q

Why does relapse occur?

A

Use microscopes to look for leukaemic cells, they all look normal, however, it is easy to miss the leukaemic stem cell
Leukaemic stem cell then produces more leukaemic cells

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20
Q

What does minimal residual disease (MRD) reflect?

A

Cellular resistance mechanisms, pharmacokinetic resistance, dosage and compliance and other unknown factors
Can be done as early as 28 days
Use pre-defined time-points

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21
Q

What are the leukaemic fingerprints in B-cell ALL and T-cell ALL

A

Ig heavy chain rearrangements

TCR rearrangements

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22
Q

What do you measure in MRD?

A

Leukaemic fingerprints

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23
Q

How do you measure leukaemic fingerprints?

A

PCR-based techniques

24
Q

What is the survival rate if you cannot detect MRD at week 4?

A

95%

25
Q

What is the survival rate if you can detect MRD at week 4?

A

78%

26
Q

What is MRD low risk patients outcome independent of?

A

NCI risk

27
Q

What is a clinical trial design to segregate ALL patients?

A

Divide them into high risk, intermediate risk and standard risk based on NCI risk for the first 28 days
Then segregate them by MRD and in the high risk group, randomly segregate them into standard vs. intensive treatment and in the low risk randomly separate them into strand vs reduced intensity

28
Q

What happens if you decrease the intensity of drug in patients with low MRD?

A

There is no difference in survival between reduced and standard dose

29
Q

What happens if you increase the intensity of drug in patients with high MRD?

A

The higher dose was more effective

30
Q

What is the phenotype of Hodgkin lymphoma?

A

Malignant mass in the lymph gland, causes enlarged lymph gland
Most of the lymph node mass is non-tumour cells which the tumour cells have attracted

31
Q

What is the treatment schedule for limited stage Hodgkin lymphoma?

A

3 cycles of chemotherapy (e.g. ABVD) +/- radiotherapy

32
Q

How successful is treatment for limited stage Hodgkin lymphoma?

A

90% cure

33
Q

What is the treatment schedule for advanced stage Hodgkin lymphoma?

A

6 cycles of chemotherapy (e.g. ABVD) +/- radiotherapy

34
Q

How successful is treatment for advanced stage Hodgkin lymphoma?

A

70% cure

35
Q

What is the issues with Hodgkin lymphoma treatment?

A

Relapse

Toxicity

36
Q

If a patient relapses with Hodgkin lymphoma, what treatment do they get?

A

Stem cell transplants and more intensive chemotherapy

37
Q

Name 4 drugs in ABVD

A

Adriamycin
Bleomycin
Vinblastine
Dacarbazine

38
Q

What are the side effects of adriamycin?

A

Hair loss
Nausea and vomiting
Myelosuppression
Cardiotoxicity

39
Q

What are the side effects of bleomycin?

A

Shivers and shakes
Skin pigmentation
Lung toxicity

40
Q

What are the side effects of Vinblastine?

A

Nausea
Myelosuppression
Neuropathy

41
Q

What are the side effects of dacarbazine?

A

Nausea and vomiting
Myelosuppression
Phlebitis

42
Q

How much does Hodgkins lymphoma treatment with ABVD and radiotherapy increase your chances of developing breast cancer?

A

10 fold

43
Q

When has a patient with Hodgkin’s lymphoma officially cured?

A

If the disease hasn’t come back for 15 years

44
Q

When do Hodgkin lymphoma patients tend to develop secondary malignancies?

A

After 30 years

45
Q

What is a clinical trial design for Hodgkin lymphoma patients?

A

Give 3 cycles of chemotherapy and then complete a PET scan
If they are PET positive, give them another cycle of chemotherapy and radiation
If they are PET negative, randomise them and give one group no further treatment and the other group another round of chemotherapy and radiation

46
Q

What was the results from the Hodgkin lymphoma PET scan clinical trial?

A

there is no statistical significance between PET negative patients having more therapy and not
Could be causing more longer damage to give more treatment for the couple of people it helps

47
Q

What is the new Hodgkin lymphoma stratification clinical trial?

A

Give them two cycles of ABVD and do a PET scan
PET positive - intensify treatment
PET negative - randomise and give one 4 more cycles of ABVD and the other 4 cycles of AVD (decrease toxicity)

48
Q

What was the results of the new Hodgkin lymphoma stratification clinical trial?

A

The removal of bleomycin decreased disease toxicity without affecting the chances of relapse in patients with PET negative

49
Q

Name a mitotic spindle inhibitor for T cell lymphoma and Hodgkins lymphoma

A

Brentuximab

50
Q

What does brentuximab target?

A

CD30

51
Q

How does Brentuximab work?

A

The drug is attached to the linker of the monoclonal antibody
Binds to CD30 on the cell surface
Internalised into the cancer cell along with the drug
Diffuses through the cytoplasm to the lysosome
Lysosome delinks the linker molecules
Cytotoxic drug inhibits the mitotic spindle

52
Q

How much did Brentuximab decrease the amount of deaths?

A

34%

53
Q

Name a DNA damaging drug for acute myeloid leukaemia

A

Gemtuzumab

54
Q

What does Gemtuzumab target?

A

CD33 on AML cell surface

55
Q

How does Gemtuzumab work?

A

Binds to CD33 on cell surface with a DNA damaging agent attached to the linker region of the monoclonal antibody
The monoclonal antibody is internalised
DNA damaging agent is released into the lysosome
Causes single or double strand breaks
Causes apoptosis through the release of cytochrome C

Cancer Pharmacology (13 decks)

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