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Chronic Myelogenous Leukemia (CML) Information

  • Chronic myelogenous leukemia (or CML) is a form of chronic leukemia characterized by increased production of myeloid cells in the bone marrow. It is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome. It is traditionally treated with chemotherapy, interferon and bone marrow transplantation, although a specific inhibitor (imatinib mesylate) has radically changed the management...
  • Patients are often asymptomatic at diagnosis, presenting incidentally with an elevated white blood count on a routine laboratory test. Symptoms may include: malaise, low grade fever, increased susceptibility to infections, anemia and thrombocytopenia with resultant bruising (although an increased platelet count, thrombocytosis, may be a feature). Splenomegaly may also be seen.

    The disease may remain dormant for years, but a proportion proceed to accelerated phase (in which the disease progresses rapidly) or transform to overt blast crisis, which may have the symptoms and risks of acute myelogenous leukemia (AML) or Philadelphia chromosome positive acute lymphoblastic leukemia (ALL), depending on the hematopoietic lineage that is involved in the transformation.

    Chronic phase CML is treated with Imatinib (marketed as Gleevec or Glivec; previously known as STI-571). In the past, hydroxyurea, alkylating agents (e.g. cytarabine), interferon alfa 2b and steroids were used, but this has been replaced by Imatinib. Imatinib is a new agent approved by the US FDA in 2001 which specifically targets the abnormality caused by the Philadelphia chromosome. It is better tolerated and more effective than previous therapies. Bone marrow transplants were also used as initial treatment for CML before Imatinib and can be curative.

    A new Drug, dasatinib (marketed as Sprycel; previously known as BMS-354825) was approved by the US FDA in June 2006 for use in patients with CML who are no longer responding to, or who can no longer tolerate, therapy with imatinib. [1]

    Various combinations of the different treatment modalities are being explored. In 2005, Bocchia et al reported favourable results of vaccination with the bcr-abl p210 fusion protein in patients with stable disease, with GM-CSF as an adjuvant. Two other drugs, ceflatonin (homoharringtonine) and AMN 107 (nilotinib) are currently in active clinical trials in patients with Chronic Myeloid Leukemia (CML) who have developed resistance to Imatinib.

    Blast crisis carries all the symptoms and characteristics of either acute myelogenous leukemia or acute lymphoblastic leukemia, and has a very high mortality rate. This stage can most effectively be treated by a bone marrow transplant after high-dose chemotherapy. In young patients in the accelerated phase, a transplant may also be an option. However the likelihood of relapse after a bone marrow transplant is higher in patients in blast crisis or in the accelerated phase as compared to patients in the chronic phase.

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