Haematological Malignancies (1) Flashcards
What is patient stratification?
Separate people into groups based on their genetic mutations and therefore the ability for a cancer cell to be treated with certain therapies
What cells does the lymphoid compartment make?
T cells
B cells
NK cells
Give examples of cells which go down the myeloid compartment
Red cells
Neutrophils
Platelets
Name the main types of haematological cancers
Chronic myeloid leukaemia Chronic myeloproliferative disorders Acute myeloid leukaemia Acute lymphoblastic leukaemia Lymphomas Chronic lymphocytic leukaemia Myeloma
Where does acute myeloid leukaemia occur?
In the primitive cells
Where does acute lymphoblastic leukaemia occur?
In the primitive cells of the lymphoid lineage
Where does myeloma occur?
In plasma cells
What is the most aggressive form of cancer in humans?
Burkitt lymphoma
What is the doubling time of Burkitt lymphoma?
Less than 24 hours
How many cases of Burkitt lymphoma can be cured?
90%
What percentage of child patients can be cured from acute lymphoblastic leukaemia?
90%
What percentage of young patients can be cured from Hodgkins lymphoma?
90%
What is the survival time for patients with multiple myeloma?
10 years with a good quality of life
What percentage of people are cured from acute myeloid leukaemia?
97% in some forms
10% in other forms
What side effects can occur in response to haematological treatments?
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
When do you typically respond well to chemotherapy is you have ALL?
If you are over the age of 1 but under 10
If your white cell count was less than 50
What are the 3 components of risk stratification?
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
What is the NCI risk criteria based on?
Age and white cell count at presentation
Cytogenetics
Microscopic speed of clearance of leukaemic cells
Why does relapse occur?
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
What does minimal residual disease (MRD) reflect?
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
What are the leukaemic fingerprints in B-cell ALL and T-cell ALL
Ig heavy chain rearrangements
TCR rearrangements
What do you measure in MRD?
Leukaemic fingerprints
How do you measure leukaemic fingerprints?
PCR-based techniques
What is the survival rate if you cannot detect MRD at week 4?
95%
What is the survival rate if you can detect MRD at week 4?
78%
What is MRD low risk patients outcome independent of?
NCI risk
What is a clinical trial design to segregate ALL patients?
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
What happens if you decrease the intensity of drug in patients with low MRD?
There is no difference in survival between reduced and standard dose
What happens if you increase the intensity of drug in patients with high MRD?
The higher dose was more effective
What is the phenotype of Hodgkin lymphoma?
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
What is the treatment schedule for limited stage Hodgkin lymphoma?
3 cycles of chemotherapy (e.g. ABVD) +/- radiotherapy
How successful is treatment for limited stage Hodgkin lymphoma?
90% cure
What is the treatment schedule for advanced stage Hodgkin lymphoma?
6 cycles of chemotherapy (e.g. ABVD) +/- radiotherapy
How successful is treatment for advanced stage Hodgkin lymphoma?
70% cure
What is the issues with Hodgkin lymphoma treatment?
Relapse
Toxicity
If a patient relapses with Hodgkin lymphoma, what treatment do they get?
Stem cell transplants and more intensive chemotherapy
Name 4 drugs in ABVD
Adriamycin
Bleomycin
Vinblastine
Dacarbazine
What are the side effects of adriamycin?
Hair loss
Nausea and vomiting
Myelosuppression
Cardiotoxicity
What are the side effects of bleomycin?
Shivers and shakes
Skin pigmentation
Lung toxicity
What are the side effects of Vinblastine?
Nausea
Myelosuppression
Neuropathy
What are the side effects of dacarbazine?
Nausea and vomiting
Myelosuppression
Phlebitis
How much does Hodgkins lymphoma treatment with ABVD and radiotherapy increase your chances of developing breast cancer?
10 fold
When has a patient with Hodgkin’s lymphoma officially cured?
If the disease hasn’t come back for 15 years
When do Hodgkin lymphoma patients tend to develop secondary malignancies?
After 30 years
What is a clinical trial design for Hodgkin lymphoma patients?
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
What was the results from the Hodgkin lymphoma PET scan clinical trial?
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
What is the new Hodgkin lymphoma stratification clinical trial?
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)
What was the results of the new Hodgkin lymphoma stratification clinical trial?
The removal of bleomycin decreased disease toxicity without affecting the chances of relapse in patients with PET negative
Name a mitotic spindle inhibitor for T cell lymphoma and Hodgkins lymphoma
Brentuximab
What does brentuximab target?
CD30
How does Brentuximab work?
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
How much did Brentuximab decrease the amount of deaths?
34%
Name a DNA damaging drug for acute myeloid leukaemia
Gemtuzumab
What does Gemtuzumab target?
CD33 on AML cell surface
How does Gemtuzumab work?
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
