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How can chronic myelogenous leukaemia (CML) be treated?

Q: I am a 61 years old man who has been diagnosed with chronic myelogenous leukaemia (CML) stage one and taking Gleevec QD 400 mg. My white cells were within normal range in 4 weeks. Do I still have cancer metastasis while my lab reports are normal?

A:Chronic myeloid (or myelogenous) leukaemia is a type of myeloproliferative disorder, which is characterised by the overproduction of granulocytic cells. In more than 90% of cases the disease is caused by a specific mutation in a single gene, which disturbs the cell cycle resulting in uncontrolled proliferation of the cells. The specific drugs used for treatment target the protein produced by this mutation resulting in normalisation of the cell count, both in the bone marrow and peripheral blood and reduction/disappearance of the abnormal chromosome.

The disease generally passes through 3 phases (though not in all patients) called the chronic, accelerated and blastic phase. The chronic phase tends to be asymptomatic with a gradual rise in the total white cell count and an increase in the size of the spleen (splenomegaly). Treatment at this stage aims to control symptoms resulting from a decrease in haemoglobin (anaemia), infections or bleeding, secondary to a fall in the number of platelets. With current therapy, the chronic phase may last for nearly a decade. Ultimately, patients enter into a transitional accelerated phase, which may last, from 3 to 6 months. It is characterised by unresponsiveness to treatment with increase in cell count and spleen size. This phase then culminates into a blast crisis, akin to acute leukaemia not responsive to treatment, where blast cells increase in the blood &/or bone marrow. This used to occur within 3-5 years of diagnosis but is now generally delayed with improved therapy. Patients have symptoms of severe anaemia, bleeding, recurrent infections and there may be infiltration of organs and other soft tissue by the increased white cells (leukaemic infiltration).

The aim of therapy in CML is to normalise the blood count (called hematologic remission), disappearance of abnormal chromosome (cytogenetic remission) and finally, molecular remission, where the genetic defect cannot be detected by tests like PCR. Despite the response to drugs like imatinib (Gleevec), patients often become refractory to it. The treatment given to each patient is individualised and is based on the age of the patient, presence/absence of a matched bone marrow donor, and the risk status (calculated using a formula that incorporates age, platelet count, number of peripheral blood blasts and spleen size). Using a variety of parameters, patients are classified as good- (survival 5-6 years), intermediate- (survival 3-4 years), or high-risk (survival ~2 years) and treatment is accordingly tailored.

Please discuss these issues with your haematologist who would be best placed to advise and guide you.


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