option; it is vital that each patient is aware of treatment options and their risks and benefits.

• Leukapheresis should be performed with cryopreservation of stem cells which may be used for future autologous rescue if required; it may also be necessary for treatment of leucostasis or priapism.

• Allopurinol should be commenced.

• Hydroxyurea has been drug of choice for controlling WBC, 'normalising' the FBC and reducing spleen size in chronic phase. Maintenance 1 —1.5g PO od. No effect on cytogenetics or natural history. Side effects: rash, mouth ulcers and diarrhoea.

• Interferon-a (IFN-a) at a target dose of 5 million units/m2/day SC corrects 1gg haematological abnormalities in 75% and produces complete cytogenetic response (CCR) in 10-15% and major cytogenetic response (MCR; <33% Ph+ cells) in 15-30%.

• Treatment with IFN-a is associated with prolonged time to progression and longer survival (57% at 5 years), most significantly in those with complete and major responses; adding cytarabine increases CCRs to 25-35% and improves survival.

• IFN-a side effects (malaise, febrile reactions, anorexia and weight loss, depression) reduce quality of life and not tolerable for many patients.

• Polyethylene glycol-IFN administered once weekly and has a more favourable side effect profile.

• Imatinib (Glivec®) gives better cytogenetic responses and progression free survival with fewer side effects; has changed the therapeutic algorithm in CML; a small molecule signal transduction inhibitor that specifically targets BCR-ABL and some other tyrosine kinases:

- 400mg PO od in newly diagnosed patients in chronic phase produces complete haematological response in 96%, major cytogenetic response in 83% and complete cytogenetic response in 68%; only 3% achieve a molecular remission (negative RT-PCR for BCR-ABL at 10-5-10-6).

- Most patients achieve major cytogenetic response (MCR) within first 6 months of therapy; patients with MCR have lower risk of relapse.

- Commonest side effects are myelosuppression, oedema, nausea, muscle cramps, skin rash, fatigue, diarrhoea, headache and arthralgia; most are mild to moderate and easily manageable.

- Now approved in both US by FDA, and in UK by NICE for not only IFN-a-resistant patients for all newly diagnosed patients.1

- Imatinib combined with IFN-a or cytarabine are under examination.

- Uncertainty about long term outcomes, resistance and response duration.

• Sibling-matched allogeneic stem cell transplant is treatment of choice for age <50 unless they develop a major cytogenetic response, but only 30% will have sibling match. Transplant related mortality is approximately 20%. Outcomes best in younger patients (<30) in chronic phase <1 year from diagnosis. RT-PCR for BCR-ABL is used to monitor minimal residual disease once Ph-negative engraftment is achieved.


• MUD allogeneic transplant, if available, should be used for <25 age group and considered <40 years but transplant related mortality rises up to 45%.

• Non-myeloablative conditioning has been used to reduce treatment related toxicity in older patients using donor lymphocyte infusions to produce a graft-versus-leukaemia (GvL) effect; it is too early to assess long term results.

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