Chronic leukaema

Question 1

What different chronic leukaemias exist?

Answer 1

chronic myeloid leukaemia: chronic cancer of RBCs and WBCs

Chronic lymphocytic leukaemias: chronic cancer caused by a progressive accumalation of functionally incompetent B lymphocytes

Question 2

CML vs CLL - age of onset

Answer 2

CML:

• adult disease
• peak age incidence 40-60years

CLL:

• occurs later in life
• increases in frequency with older age
• most common of all leukaemias

Question 3

CML: clinical features?

Answer 3

Many have no symptoms, usually presents in chronic phase

• SOB
• Immunosuppression due to marrow failure
• splenomegaly/splenic pain
• gout
• wt loss
• fever
• night sweats
• problems due to hyperleukocytosis (e.g. priapism)

Question 4

CLL: clinical features?

Answer 4

often asymptomatic and is discovered incidentally

• SOB
• Immunosuppression due to marrow failure
• splenomegaly/splenic pain
• gout
• wt loss
• fever
• night sweats

Question 5

What is the natural progression of CML?

Answer 5

The natural progression of CML is as follows: 
chronic phase (intact maturation for 3-5yrs) → aggressive/accelerated phase (process maturation slowed down, more primitive cells appear) → blast phase/crisis (stop maturation completely - AML picture).

Question 6

For CML and CLL what is the:
Blood count
Blood film
Bone marrow aspirate
Cytogenetics

Answer 6

CML:
Blood count - Hb low or normal, WBC high, Platelets low or normal or raised

Blood film - neutrophilia, bigger more mature and blast like WBC

Bone marrow aspirate - increased cellularity

Cytogenetics: BCR-ABL 1 positive, philadelphia chromosome (9:22 translocation)

CLL:
Blood count - same as CML but WCC may be v high

Blood film: increase in lymphocytes

Bone marrow aspirate: heavily infiltrated with lymphocytes

Question 7

Describe the management of CML

Answer 7

1st line for chronic phase: Imatinib (tyrosine kinase inhibitor) prevents the action of the BCR-ABL fusion protein, i.e.this is the abnormal protein produced by the Ph mutation.

95% of patients will respond to the drug
70-80% of these have no detectable BCR-ABL in the blood

This treatment can be continued indefinitely

The drug is usually well tolerated, but side effects can include nausea, headaches, rashes, cytopaenia, cramps, myelosupression; resistance can sometimes develop.
(18 months of a ~nib drug will completely eradicate the Ph mutation in 76% of patients)

Interferon-α is sometimes given to patients who don’t have the Ph mutation.

Stem cell transplantation (SCT) will cure approx 70% of patients. However there is a risk of death from graft versus host disease, and infection.

(The use of SCT has declined since the advent of Imatinib,however it is still indicated in those with a poor response to the drug, i.e. those who do not have the Ph mutation.)

Question 8

Describe the management of CLL

Answer 8

Chlorambucil has been considered the drug of choice for first-line therapy of CLL, and when combined with prednisone, chlorambucil is associated with an initial response rate of 60-90% and a complete response in up to 20% of all patients.