Chronic Leukaemia Flashcards
What is chronic leukaemia
-proliferation of mature, ineffective cells in the bone marrow, peripheral blood and various organs
- resistant to apoptosis
- has indolent presentation - so normally found by mistake
- -presents later in life
- cytogentic abnormalities present in large proportion of patients - drives treatment
What are the two types of chronic leukaemia
- Chronic myeloid leukaemia (CML)
- Chronic Lymphoblastic leukaemia (CLL)
What is the pathophysiology of CML
- Phildaphila chromosome is translocation of the genetic material between chromosome 9 and 22 containing BCR-ABL oncogene on chromosome 22
- This promotes proliferation of myeloid cells thereby:
- increasing tyrosine kinase activity,
- alters multiple signal transduction pathway
- causes malignant transformation of myeloid cells
What are the different phases of CML
Chronic phase
Later phase - more aggressive
What is the treatment of CML
1st generation tyrosine kinase inhibitor:
-Imatinib
2nd generation tyrosine kinase inhibitor:
- dasatinib
- nilotinib
- bosuntinib
What is the first line treatment of CML and what are its advantages
Imatinib - first line treatment for BCR-ABL
it has no interaction with:
- hypertension
- prolonged QT interval
- diebetes
- GI bleeding
- abnormal liver function
What is BCR-ABL gene
It is an oncogene that promotes cell survival and proliferation
What are the factors that affect inital treatment choice of chronic leukaemia
- high or intermediate ELTS or SOKAL score
- early treatment discontinuation
- co-morbidities
How do you measure response to treatment in CML
- molecular or cytogenetic monitoring is required
- optimal response defined as BCR-ABL transcript level
- cytogenetics: >65% Ph -ve at 3 months and at 12 months 100%
- duration of treatment - individual patient factors
What are common TKI side effects
- Fatigue
- Insomnia/sleeping problems
- Subconjuctal haemorrage in eye oedema
What monitoring is required with TKI
-can cause hypertension
need to check:
- blood pressure and lipids before starting
- measure heart before and during treatment
- offer CV assessment
Why would you switch TKI treatment
due to adverse drug reaction or resistance
What ways can cancer cells develop drug resistance
- multidrug resistance gene (MDR)
- the tumour pumps drug out of the cell so the drug does nor work effectively - Plasma protein binding
- binds to TKI so the TKI has no effect - mutation in the BCR-ABL gene
- so tumour becomes resistant to Imatinib but the mutation can be targeted by 2nd gen TKI - Activation of downstream pathway to continue signal transduction
- Amplification of BCR-ABL gene
- so the drug becomes ineffective
What is chronic lymphocytic leukaemia (CLL)
- incurable disease with indolent development
- different sub-types: B-cell origin (most common) and T-cell origin
What is the staging system of CLL
- RAI system
- BINET system
Early staging:
-lymphocytes in peripheral blood and bone marrow only
Late staging:
- lymphocytosis
- anaemia
- thrombocytopenia
