Week 2- advanced in haematological therapies Flashcards
How does chemotherapy and radiotherapy work?
They damage the DNA of dividing cells. Therefore the body recognises them as damaged and performs apoptosis. Often it involves a protein in the cell nucleus called P53.
What can mutations in P53 cause?
Difficulty in treating the condition with chemo and radiotherapy.
Why is a lower dose of chemotherapy better?
It means you don’t have as much toxicity side effects. You don’t get inflammation etc.
Why do lymphoma, chronic lymphocytic leukaemias and acute leukemias respond to chemotherapy better than most other cancers?
Lymphocytes are keen to undergo apoptosis in the normal lymph node. Therefore when triggered by chemo/radiotherapy they are keen to conform.
Acute leukaemia means the cells are dividing quickly and are therefore susceptible to chemo/radiotherapy.
What are the side effects seen with chemo? why do these occur?
Normal cells also undergo division and therefore are also susceptible to the chemotherapy.
Hair loss, N & V, neutropenic infection, tiredness.
Long term effects can be heart damage, lung damage and other cancers.
What supportive therapy is given to people on chemotherapy?
Broad spectrum ABs
Red cell and platelet transfusions
Growth factors (GCSF)
Prophylactic antibiotics and antifungals (itraconazole).
What sort of scan is used in Hodgkins lymphoma to see how well chemotherapy is working?
PET scans- uses radiolabelled glucose to see which tissues uptake it the most. Cancer cells will have a high uptake of glucose.
What agents are used for targeted therapies in the treatment of haematological malignancies?
Monoclonal antibodies
Biological agents
Molecularly targeted treatments
How do monoclonal antibodies work in the treatment of haematological malignancies?
They attack cells which express certain antigens. Meaning they avoid attacking healthy cells unlike in chemotherapy.
What is the drawback of monoclonal antibodies being used as treatment?
They are currently only used as additive treatment to chemotherapy so you still get the same side effects due to the chemo. However they do improve outcome.
How does ritixumab work? (it is a monoclonal AB)
When the antibody binds to CD20 (expressed on non-hodgkin lymphoma and chronic lymphocytic leukaemia), it has an Fc receptor that sticks out. This then interacts with the immune system and T cells come and destroy the antigen-antibody complex.
How do other anti B cell antibodies differ from ritixumab?
They are more direct at killing. When they bind they kill the malignant cells rather than activating the immune system to do so.
Give some examples of other anti B cell antibodies?
When are they used clinically?
Ofatumunab (Azerra).
Obinutumab (Gazyvaro).
Used in patients not responding to ritixumab.
Describe the use of Brentuximab Vedotin in Non-Hodgkin lymphoma?
A chemotherapy drug is attached to the antibody and targets the CD30 protein expressed in Hodgkins cells and some T cells non-hodgkin lymphomas.
Describe biological treatments?
They use a range of different modes of actions to stop cancers. However they are not targeted therapies and therefore you get side effects.
The best examples are proteasome inhibitors and IMIDs
What is the proteosome?
The organelle in the cell responsible for recirculation of amino acids. Cells recognise proteins need to be broken down by sticking ubiquitin onto them.
How do proteasome inhibitors work?
They block the proteasome meaning you get accumulation of toxic intracellular products and therefore apoptosis occurs.
When are proteasome inhibitors used?
They are used in myeloma, mantle cell non-hodkin lymphoma and low grade non-hodgkin lymphoma.
What are IMIDs?
How do they work?
They are a derivative of thalidomide. Their mode of action isn’t well understood.
Who are IMIDs used for?
Used for patients with low grade NHL and CLL not responding to chemotherapy.
What side effects can you experience with IMIDs?
Nerve damage
Risk to fetus
Effects on blood counts
May cause other cancers.
What translocation causes chronic myeloid leukaemia?
The philledelphia translocation
What molecular therapies are used in the treatment of chronic myeloid leukaemias?
Tyrosine kinase inhibitors e.g. Imatinib, nilotinib,
dasatinib, ponatinib
Which drugs can affect B cell signalling pathways?
What cancers are these effective in?
Ibrutinib (Imbruvica) and Idelalisib (Zydelig)
Effective in low grade NHL and B cell CLL that don’t respond to ritixumab or chemo.
