Week 2 - G - New treatments for blood cancers - Chemo/radio, Monoclonal, Molecular targeted- AML/ALL/CML/CLL/NHL/HL Tx Flashcards
Which type of lymphomas are not curable?
These would be the low grade non hodgkins lymphomas
There has been vast improvements in the treatment of haematological malignancies in the last 10/15 years and patient prognosis and survival has greatly improved How do chemotherapy and radiotherapy work?
Chemtherapy damages the cancer DNA as the cell divides (mitosis) and the cell recognises it is damaged beyond repair and therefore undergoes apoptosis -programmed cell death
What is the protein that is often involved in the programmed cell death in patients? usually is the protein that causes apoptosis after the cell is damaged from chemo/radiotherapy
The p53 gene protein (TP53) is a tumour suppressor gene that is involved in the process of programmed cell death in response to cellular damage
In what type of leukaemia can p53 mutations cause great difficulty for treatment? Where does the deletion of p53 take place?
This can cause problems in the treatment of chronic lymphoctyic leukaemias Deletions in part of the short arm of chromsome 17 -17p deletions cause there to be an absence of p53 resulting in uncontrolled proliferation of the tumour cell even when normal chemotherapy is applied
How is the chromsome mutation identified in cancers?
Cytogeneitc anaylsis would be used to identify if there were any chromsomal abormalities
What is the usual treatment of chronic lymphocytic anaemia? What is the treatment if there are del17p/p53 mutations?
Usual treatment is FCR - multi-agent chemo FLudarabine, cyclophosphamide and rituximab If there is a del17p/p53 mutations, these agents will not work as they rely upon p53 being active and there ibrutinib is used - these affect the B cell signalling pathway and dont rely upon p53
Is lower dose or higher dose chemotherapy usually preferred and why?
Lower dose chemotherapy is usually preferred as it damages the cell enough to make it undergo apoptosis and therefore no inflammation occurs High dose chemotherapy however necroses the cell causing it to swell and lyse causing inflammation at the site
Why do lymphoma/CLL and acute leukaemia respond better than most other cancers to chemo and RT ?
This is because in lymphomas and chronic lymphocytic leukaemias there is an increase in lymphocytes obviously - these cells are very keen to undergo apoptosis and therefore when chemo/radiotherapy triggers cell damage, apoptosis is likely to occur In acute leukaemias, the cells are rapidly dividing meaning the therapy will target all the cells at once
Unfortunately, both chemo and radiotherapy also damages normal cell tissue resulting in some side effects What are the immediate and long term effects of chemo/radiotherapy?
Immediate effects of chemo/radiotherapy - the person will be extremely tired, also associated hair loss, naursea and vomiting and increased risk of neutropenic infection Long term effects of chemo/radiotherapy - there could be heart and lung damage and other cancers are more common after chemo/radiotherapy
Ideally due to the effects of chemo and radiotherapy affecting normal cells as well as the cancer cells, there is research into more cell-targeted therapies which treat the leukaemia/lymphoma directly A major increase in survival of the haematological malignancies is the big increase in supportive therapy What are some of the supportive therapy measures that are carried out?
* There is immediate IV antibiotics for any signs of neutropenic sepsis * Red cells and platelet transfusions are available * Prophylactic antifungals are given to prevent the rise of any fungal infection in the immunosupprssed * Growth factors - granulocyte colony stimulating factors can also be given
To start with - there is an increased improvement in supportive care of neutropenic sepsis Emergency treatment of neutropenic sepsis. Urgent treatment-use of standardised guidelines in all hospitals.
- What is neutropenic sepsis defined as and what is the treatment?
- What are the signs of sepsis?
Defined as sepsis + neutrophil count <0.5 or <1 in a patient who has had chemotherapy in the past 21 days Signs of sepsis
- S - shivering/fever/very cold
- E - extreme pain or discomfort
- P - pale or discoloured skin
- S - sleepy difficult to rouse
- I - i feel like i might die
- S - SOB
In sepsis there is a systemic inflammatory response to the bacteria in the blood stream What is the criteria for diagnosing sepsis using the SIRS? (Systemic inflammatory response syndrome)
Two or more than of:
- Temperature >38 or 90bpm
- Respiratory rate >20bpm or PaCO2 <4.3kPa (32mmHg)
- WBC >12x10^9 or <4x10^9 or >10% immature forms on microscopy
If patient has had chemo in the last 3 weeks and temp>/38degrees or they have a SIRS score of >/= 2, what should be done immediately?
The patients should have bloods taken and sent for culture and started on antibiotics immediately without waiting for blood results to come back
When patients have neutropenic spesis, SEWS score normally very high WHat is the treatment for the patient?
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if a patient is suspected of a hickman line infection, what is added to the piperacilin and tazobactam treatment regime?
Add vancomycin as gram +ve organisms suspected
Targeted therapies are aimed at targeting the specific leukaemic / lymphoma cells How do mnoclonal antibodies work? what is the best example of a monoclonal antibody and what does it target?
Monoclonal antibodies work by only affecting cells which express the target protein The best example is rituximab Rituximab binds specifically to CD20 on B cells and this is therefore cytotoxic to the B cells in NHL
Unfortunately most monoclonal antibody are currently used in combination with chemotherapy rather than instead of-so same risks! More effective than chemotherapy alone. Where on the immunoglobulin does the antigen bind?
The antigen binds to the antigen binding site present on the antibody - When the antibody binds to Cd20, the Fc part that sticks out activates the immune system – complement, T cells etc
Biological agents have been superceded by more targeted therapy so dont really need to know What was the third type of targeted therapy again?
Molecularly targeted treatments are the other the type of targeted therapy
Drugs affecting the B cell signalling pathway are effective in low grade NHl and B cell CLL that don’t respond to rituximab and chemotherapy Give an example of a drug affecting this pathway? When is it used?
- Ibrutinib - used if non responding to fludarabine + cyclophosphamide + ritxumab in CLL
- Or to R-CHOP in NHL (idelasib is another type of B cell signalling pathway inhibitor)
- First line if p53 mutation or deletion in short arm of chromosome 15 (17p del)
- These drugs don’t require p53 to work
What cells are seen in?
These are Reed sternberg cells - see the mirror image nuclei here
