chronic leukaemia

What genetic abnormality defines CML?

The BCR-ABL fusion gene caused by t 9 22 Philadelphia chromosome

What type of disease is CML classified as?

A myeloproliferative neoplasm

What are common presenting symptoms of CML?

• Fatigue

• weight loss

• night sweats

• abdominal fullness

• anorexia

How is CML often diagnosed?

Incidentally on routine blood tests

What is the mechanism of BCR-ABL?

A constitutively active tyrosine kinase activating multiple growth pathways

What was the first TKI used in CML?

Imatinib

What is a key toxicity concern with Nilotinib and Ponatinib?

Cardiovascular risk requiring monitoring

What investigation is used to assess pleural effusions in TKI therapy?

Chest X-ray

What is the management approach for TKI side effects?

Temporary interruption and slow re-titration or switching TKIs

What is the treatment pathway for CML that has had inadequate response?

Second-line TKI then third-line TKI then transplant if suitable

What is the long-term goal for many CML patients on TKIs?

Treatment-free remission

What is CLL?

A malignancy of mature B-cells driven by dysregulated BCR signalling

What are the two major biological subgroups of CLL?

Mutated IGHV and unmutated IGHV

Which genetic abnormality predicts poor response to chemo-immunotherapy in CLL?

TP53 mutation or 17p deletion

What is the most common age group for CLL diagnosis?

Over 75 years

What are common presenting symptoms of CLL?

• Recurrent infections

• lymphadenopathy

• fatigue

• bruising

• night sweats

• weight loss

What is the initial management strategy for many CLL patients?

Active monitoring watch and wait

What is the mechanism of anti-CD20 monoclonal antibodies?

Bind CD20 causing Antibody-dependent cellular cytotoxicity (ADCC) , Complement-dependent cytotoxicity (CDC) and apoptosis

What are key side effects of rituximab or obinutuzumab?

• Infusion reactions

• Cytokine release syndrome (CRS)

• Tumour lysis syndrome (TLS)

• infection risk

• viral reactivation

Why is chemo-immunotherapy no longer preferred in CLL?

Targeted therapies give better outcomes especially in TP53 or 17p deleted disease

What is the mechanism of BTK inhibitors?

Block BCR signalling to inhibit CLL cell survival

What is the mechanism of Venetoclax?

A BCL-2 inhibitor that triggers apoptosis

What is the major risk when initiating Venetoclax?

Tumour lysis syndrome due to rapid tumour kill