Chronic Myeloid Leukaemia Flashcards
Describe chronic leukaemia’s
Slow growing, asymptomatic for long time
Proliferation of mature, resistance to apoptosis, ineffective cells in the bone marrow, peripheral blood + various organs
Present in later life
Cytogenic abnormalities
Describe chronic myeloid leukaemia
Proliferative disorder from myeloid progenitor lineage
Translocation of genetic material between chromosome 22 + 9 = forms Philadelphia chromosome containing oncogene BRC-ABL
Present in ALL CML patients
What does the Philadelphia chromosome containing BRC-ABL?
Increased tyrosine kinase activity
Alters multiple signal transduction pathways
Malignant transformations of myeloid cells
Describe the treatment of CML
1st line = 1st generation TKI = Imatinib
2nd line = 2nd generation TKI = Dasatanib/Nilotunib/Bosutinib
This has replaced the use of allogenic transplants as 1st/2nd line
When are 2nd generation TKI used 1st line?
Used for a subgroup of patients when rapid response is advantageous
BUT higher toxicity + cost
Those who want to be pregnant soon = teratogenic = can’t be taken whilst pregnant/breastfeeding
Poor prognostic score
Younger
What is good about Imatinib?
Good to be used for patients with other conditions
Describe how to measure response
Molecular monitoring = BCR-ABL transcript levels = 1% (complete) + <0/01% deep molecular response
Cytogenic = absence of Philadelphia chromosome = complete response
Only STOP treatment when above achieved BUT most patients looking at maintaining
Describe the SEs of TKIs
Skin +S/C tissue = rash, dry, itch, alopecia + sweats
Musculoskeletal = myalgia
GI = N+V, anorexia, constipation + diarrhoea
Hepatobiliary = abnormal LFTs, pancreatitis
Renal = impairment
Haematological = bone marrow suppression
Infection = increased risk of infection
Metabolism/endocrine = thyroid function abnormalities, diabetes, gynaecomastia, erectile dysfunction + effects of fertility
Neurological = headache, migraine + dizziness
Cardiorespiratory = HT, HF + QT prolongation
Describe how to manage SEs
Loperamide for diarrhoea
Diuretics in peripheral oedema
Oral steroids of pleural effusion
Corticosteroids for elevated liver enzymes
Topical steroids for symptomatic treatment of rash
Antihistamines
Dose reduction
Describe TKI resistance
2nd generation can be used = broader spectrum of action
Genetic testing = identifying mutations = choose drug which is best
Mutations: drug efflux, BCR-ABL mutations, activation of downstream pathways (proliferation continues) + BCR-ABL gene amplification (increased expression)
Describe how to switch TKI
Considered if treatment failure on 1st line
Choice of 2nd line in resistant patient guided by BCR-ABL KD mutation analysis
Dose escalation to 600mg in suboptimal response = IF good tolerance
Absence of mutations = pre-existing co-morbidities + SE profiles guide choice
