How is chronic myelogenous leukemia (CML) treated?

Updated: May 23, 2021
  • Author: Emmanuel C Besa, MD; Chief Editor: Sara J Grethlein, MD, FACP  more...
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Typically, CML has three clinical phases: an initial chronic phase, during which the disease process is easily controlled; then a transitional and unstable course (accelerated phase); and, finally, a more aggressive course (blast crisis), which is usually fatal. In all three phases, supportive therapy with transfusions of red blood cells or platelets may be used to relieve symptoms and improve quality of life.

The chronic phase varies in duration, depending on the maintenance therapy used: it usually lasts 2-3 years with hydroxyurea (Hydrea) or busulfan therapy, but it may last for longer than 9.5 years in patients who respond well to interferon-alfa therapy. Furthermore, the advent of tyrosine kinase inhibitor (TKI) therapy has dramatically improved the duration of hematologic and, indeed, cytogenetic remissions. For most patients with chronic-phase CML who are treated with TKIs, median survival is expected to approach normal life expectancy. [1, 14]

In Western countries, 90% of patients with CML are diagnosed in the chronic phase. These patients’ white blood cell (WBC) count is usually controlled with medication (hematologic remission). The major goal of treatment during this phase is to control symptoms and complications resulting from anemiathrombocytopenia, leukocytosis, and splenomegaly. The standard treatment of choice is the first-generation TKI imatinib mesylate (Gleevec), which is a specific small-molecule inhibitor of BCR/ABL in all phases of CML.

The second-generation TKIs nilotinib (Tasigna), dasatinib (Sprycel), and bosutinib (Bosulif) are approved as first-line treatment for CML in the chronic phase. Although all those agents produce a higher rate of deep molecular response and provide better early control of disease than imatinib, the benefits and risks of these newer agents compared with imatinib, as well as their comparative long-term safety profiles, have not yet been established. [15, 18]

A significant “adverse effect” of imatinib is its high cost (approximately $100,000 annually), which is especially significant given the long duration of treatment. A generic formulation is available, but its efficacy for first-line treatment  of CML has been questioned. [19] However, the European Stop TKI Study (EURO-SKI), found that stopping TKI therapy is feasible and that about half of patients remain free from relapse after 2 years of follow-up. In EURO-SKI, the optimal duration of TKI therapy prior to discontinuation was 5.8 years or longer. [20]  Guidelines increasingly suggest considering treatment discontinuation in carefully selected patients [21, 22, 23] (see Long-Term Monitoring, below).

Some patients with CML progress to a transitional or accelerated phase, which may last for several months. The survival of patients diagnosed in this phase is 1-1.5 years. This phase is characterized by poor control of blood counts with myelosuppressive medication and the appearance of peripheral blast cells (≥15%), promyelocytes (≥30%), basophils (≥20%), and platelet counts less than 100,000 cells/μL unrelated to therapy.

Many of the treatment decisions in CML, including possible hematopoietic stem cell transplantation [24] and investigative options for younger patients, are extremely complex and in constant flux. Individualized decisions should be made in conjunction with consultation with physicians familiar with the recent literature. New agents that are currently under study may prolong the survival of patients with CML and offer the possibility of eventual cure. Physicians should refer their patients to tertiary care centers for clinical trials involving these therapies.

For more information, see Chronic Myelogenous Leukemia Treatment Protocols.

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