Chronic Leukaemias Flashcards
What are chronic leukaemias?
Increased proliferation of mature, ineffective cells in the bone marrow, peripheral blood and organs that are resistance to apoptosis.
How are chronic leukemias typically diagnosed?
Patients often have an incidental diagnosis, it is not always appropriate to initiate treatment straight away. The philidelphia chromosome is a key diagnostic, as it is a common abnormality of chronic leukaemia cancer cells
What is chronic Myeloid cancer?
A proliferative disorder from myeloid progenitor, leads to translocation of genetic material from chromosome 9-22 which forms the BCR-ABL oncogene on chromosome 22 (philadelphia chromosome) to increase tyrosine kinase activity which alters multiple signal pathways and causes malignant myeloid cell proliferation
How is chronic myeloid leukaemia treated?
Tyrosine kinase inhibitors
How do tyrosine kinase inhibitors work?
They bind to tyrosine kinase ATP specific binding site, which prevents tyrosine kinases from phosphorylating ATP and initiating the signalling cascade leading to cell proliferation
Give examples of tyrosine kinase inhibitors
imatinib, dasatinib, nilotinib, bosutinib
Which factors affect initial treatment of chronic myeloid leukaemia?
- EUTOS long term survivial score - higher the score means lower survival. If score is high, earlier discontinuation of treatment is desired.
- co-morbidities and contraindications: nilotinib should be avoided in patients with prolonged QT interval/congestive heart failure, dasatinib should be avoided in pulmonary hypertension
How is response to treatment measured in CML?
- cytogenetic and molecular response rates
- low bcr-abl transcript levels
- less than 65% philadelphia chromosome positive
What is the duration of treatment for CML based on?
Individual patient parameters:
- does the patient wish to get pregnant?
- indefinite?
- at least 5 years
What are the adverse effects of TKIs?
Fatigue, insomnia, oedema, sub conjunctival haemorrhage
SCARS, rash, dry skin, alopecia, sweats, myalgia, cramp, GI effects, pancreatitis, bone marrow suppression
What can be considered if patients have adverse effects to tki therapy?
Does reduction, antihistamines, topical steroids, corticosteroids, loperamide
What must all patients have before starting tki?
CV risk assessment
How does resistance to TKI occur?
Drug efflux, drug binds to plasma proteins which leads to mutations in the gene and upregulation of an alternative signalling pathway (increased bcr-abl gene)
What is chronic lymphocytic leukaemia and which patients is it common in?
A cancer of predominantly b cell origin, most common in older age, men and is incurable
What is treatment of CLL based on?
Whether it is symptomatic, stage, age, cytogenetics. Treatment aims to induce remission and control symptoms
