Treatment for Chronic Myelogenous Leukemia (CML)
The challenge of treating newly diagnosed CML is to determine the best overall strategy to control the disease. General strategies for management include a variety of options:
- Leukapheresis, also known as a peripheral blood stem cell transplant, with stem cell cryopreservation (frozen storage) prior to any other treatment. The patient's blood is passed through a machine that removes the stem cells and then returns the blood to the patient. Leukapheresis usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any cancer cells. The stem cells then are stored until they are transplanted back into the patient.
- HLA (human leukocyte antigen) typing of all patients under age 60, as well as typing of siblings, parents, and children, if available. This procedure will determine whether a compatible donor is available for stem cell transplantation.
- Pre-treatment fertility measures (e.g., cryopreservation of semen prior to treatment; completion of a pregnancy prior to treatment) in young patients who have not completed their families.
- Interferon-alpha (INF-a) therapy.
- Chemotherapy with drugs such as hydroxyurea (Hydrea), busulfan (Myleran) or imatinib mesylate (Gleevec).
In general, CML treatment options are divided into two groups: those that do not increase survival and those that do. Chemotherapeutic drugs such as hydroxyurea (Hydrea) and busulfan (Myleran) can normalize the blood count for a period of time, but they do not increase survival. They often are used to control blood counts in patients who cannot undergo SCT or who do not respond to interferon therapy because of age or medical considerations.
Imatinib mesylate (Gleevec) is used as initial treatment for certain types CML. This drug blocks an enzyme called tyrosine kinase that causes stem cells to develop into white blood cells. It prevents abnormal cell growth, without damaging healthy cells. Other cancer therapies, such as chemotherapy, destroy healthy cells as well as cancer cells, causing unpleasant and often severe side effects. Imatinib mesylate should be used with caution in patients who have liver disease.
In June of 2006, the Food and Drug Administration (FDA) approved the oral tyrosine kinase inhibitor dasatinib (Sprycel) to treat CML that does not repond to other therapy.
In October 2007, nilotinib (Tasigna) was approved as a second-line treatment for certain types of CML in adults. This drug can be used in patients who cannot tolerate other therapies, or when the disease has progressed in spite of other treatments. Tasigna may cause serious heart problems, which may be life threatening, and approval of this medication includes an FDA black box warning for this potential side effect. Other side effects include low blood count, headache, nausea, and itching that may be accompanied by a rash.
One treatment that does impact on CML survival is allogeneic bone marrow transplantation, the use of high dose chemotherapy and radiation followed by infusion of a donor bone marrow. This procedure removes the chromosomal abnormality in a large percentage of patients and for them is curative.
In addition, there is treatment with interferon (INF). About 20 to 30 percent of patients taking interferon show elimination of the abnormal chromosome and improved survival. Recent findings also suggest that low-dose cytarabine (ara-C), in combination with interferon, may be more beneficial than interferon alone. For patients who do not respond to interferon, autologous or allogeneic stem cell transplantation is the only alternative.
Patients with advanced-phase disease may be treated with cytotoxic drugs. For example, individuals showing myeloid transformation may be given drugs that are used to induce remission in AML—that is, daunorubicin and cytarabine, with or without 6-thioguanine or etoposide. Blast cell numbers will be reduced temporarily, but they will increase again within 3 to 6 weeks. Individuals showing lymphoid transformation have a slightly better outlook. They are treated with drugs used in the management of acute lymphocytic leukemia (ALL)—that is, prednisone, vincristine, and daunorubicin, with or without L-asparaginase.
New drugs that are being studied in clinical trials of CML include homoherringtonine with interferon-alpha (INF-a), paclitaxel (Taxol), QS21 (a plant extract that heightens immune responses), and amifostin (a chemical that lessens some side effects of chemotherapy). In addition, clinical trials are evaluating the potential benefits of substances such as vaccines, monoclonal antibodies (immunologic substances that can direct the patient's immune system to kill cancer cells), and hormones (e.g., growth factors, interleukins).