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What causes CML and how can it be treated?

Q: I am 42 years old. I was diagnosed with CML 3 years ago. I am taking Imatinib 4 capsules. My spleen is normal but my blood report says that the WBC count has increased to 70 thousand and blast and immature cells are around 20% from the past 3 months.

A:Chronic myelogenous or myeloid leukaemia (CML) is a type of a blood cancer characterized by increased proliferation of the granulocytic cells (mainly neutrophils) of the blood leading to their accumulation in the blood, and later infiltration into other organs. The disease is caused by a genetic abnormality caused by a chromosome translocation abnormality that at the molecular level leads to the production of a chemical (called tyrosine kinase) responsible for the uncontrolled proliferation of these cells. The disease is divided into 3 phases and it follows a typical course of an initial chronic phase, during which the disease process is easily controlled; followed by a transitional and unstable course (accelerated phase); and, finally, a more aggressive course (blast crisis), which is usually fatal. In Chronic phase blasts are fewer than 10% of the cells in the blood or bone marrow, patients usually have rather mild symptoms and respond to standard treatments. The main aim of treatment during this phase is to control symptoms and complications due to anaemia, thrombocytopenia, leukocytosis, and splenomegaly. Newer drugs aim at delaying the onset of the accelerated or blastic phase. Accelerated phase occurs usually after 3 to 5 years (about 3 to 6 months before the blastic phase). The number of blasts in the blood or bone marrow increases and patients often have fever, poor appetite, and weight loss. Patients may not respond to treatment as well as during the chronic phase. Blast phase is the stage when the chronic leukemia changes into a very aggressive acute leukemia and is characterised by markedly increased number of blasts in the blood or bone marrow. Treatment options for people with CML depend on the phase of the disease, their age, other prognostic factors, and whether there is a potential stem cell donor with a matching tissue type. The goals of therapy are to achieve a hematologic remission (normal blood counts and physical examination, i.e. no organomegaly), to achieve cytogenetic remission (normal chromosome with no Philadelphia-positive cells), and, lately, to achieve molecular remission (negative PCR result for the bcr-abl mutation), which is an attempt for cure and prolongation of patient survival. Treatment during chronic phase aims to achieve hematologic remission, which requires 1-2 months of treatment. Once the patient goes into hematologic remission, the goal of treatment is to suppress the Ph-positive hematopoietic clone in the bone marrow for a cytogenetic remission and, hopefully, a molecular remission which may be done using interferon alfa or a stem cell transplant. Imatinib has completely changed the treatment of CML in chronic phase as it directly inhibits the molecular cause of the disease. Imatinib is superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed, chronic-phase CML. It causes remission in nearly 90% patients and these remissions may last upto 2 years. No one yet knows how long these remissions will last and whether it will actually cure people. CML cells are develop resistance to imatinib by developing newer mutations but this can be overcome by increasing the dose, by developing more selective kinase inhibitors, and developing new non–cross-resistant drugs. In the chronic phase, there is a close follow-up of patients (especially those under 30-35 years of age). If they do not go into and remain in complete remission on the drug, stem cell transpalnt (SCT) should be recommended. For older patients, a wait-and-see approach may be safer. The treatment choices in the accelerated phase are much like those used in the chronic phase. Although imatinib can lead to remissions, these do not last very long. For the most part, patients in this phase are less likely to have a long remission with any treatment. About 20% patients have some response to chemotherapy, but their remission is usually shorter than 6 months. You should discuss with your doctor, as he will be best placed to advise you.






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