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The Leukemia/Bone Marrow Transplant Program of BC

Treatment Options by Disease Type
Leukemia

Chronic Myeloid Leukemia (CML)

Drug Therapies

Hydroxyurea (Hydrea)

Hydrea is an oral medication with few significant side effects that is capable of controlling blood counts in CML. It does lead to a resolution in CML symptoms but does not prevent the inevitable progression to accelerated/blast phase disease within an average of 4-5 years.

Interferon (IFN)

IFN is given by injection on a daily basis and also controls blood counts in most patients with CML. In addition, IFN has been shown to significantly reduce the number of Philadelphia chromosome-containing cells in the bone marrow in approximately 15-20% of patients. This therapy results in a longer survival (6-7 years on average) than patients treated with hydrea.

IFN does, however, have many potential side effects. These include, fever, sweats, weight loss, fatigue, bone and muscle pain which may interfere with quality of life. Recent evidence suggests that the addition of another injectable chemotherapy drug to the IFN, cytosine arabinoside (Ara-C), may further prolong survival although it leads to even more side effects for the patient than IFN alone. Currently interferon is not used frequently because of better options such as Imatinib (see below).

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Imatinib Mesylate (Gleevec)

This is a recently-developed drug designed for patients with the Philadelphia chromosome. Imatinib is a "tyrosine kinase inhibitor" which specifically targets the chromosomal abnormality. Gleevec is taken orally and, unlike Interferon, has few side effects these may include mild nausea or diarrhea, swelling of the face and ankles, and abnormalities in liver function tests in the blood. For more product information about Imatinib, visit the Novartis website.

Preliminary results of a study comparing Imatinib with Interferon/Ara-C treatment in newly diagnosed CML patients has confirmed that during the initial 18 months of treatment, Imatinib produces a better response in the vast majority of patients. Current results indicate that patients who respond well to Imatinib may remain in remission for greater than 5 year.  Further follow-up is required.

While Imatinib is often used as the initial therapy in CML patients, and is the agent of choice in the treatment of blast phase patients, a BMT is usually recommended for patients with intermediate or high-risk CML.

Other Tyrosine Kinase Inhibitors

Newer thyrosine kinase inhibitors are in development.  Currently Dasatinib (Sprycel) and Nilotinib (Tasigna) are available for patient who do not respond well or have bad reactions to Imatinib (Gleevec).

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Blood & Marrow Transplant (BMT)

High-dose chemotherapy, with or without radiation, may rid patients of any evidence of CML. To avoid life-threatening bone marrow failure, a blood and marrow transplant (BMT) must be given to the patient after the treatment.

  • In eleigible patients, the stem cells can be obtained from a matched family member (almost always a brother or sister).
  • An unrelated donor is often sought for younger eligible patients who do not have a suitable family donor. This is done using the Canadian Unrelated Donor Bone Marrow Registry with its links to all the major international registries.

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Results

Related Donor BMT

The success rate with this procedure has been excellent although somewhat dependent upon the timing of the bone marrow transplant:

  • CML patients having a BMT within one year of diagnosis while in chronic/stable phase have a 65-70% chance of being cured
  • Patients having a BMT in accelerated phase have a 40% chance of a cure
  • Patients in the blast phase of CML are no longer considered BMT candidates in Vancouver due to the exceedingly poor outcome observed at many blood and marrow transplant centres. If patients in the blast phase can achieve a second chronic phase with treatment, a BMT may be considered.

Unrelated Donor BMT

This type of bone marrow transplant is associated with considerably more risk than when a related donor is used:

  • 45-50% of chronic/stable phase patients continue without CML recurrence
  • When the BMT is done in accelerated phase, only 20-25% of patients are alive and well two years following the BMT
  • Patients with blast phase CML are not considered candidates for unrelated donor blood and marrow transplant. If patients in the blast phase can achieve a second chronic phase with treatment, a BMT may be considered.

Reduced Intensity Conditioning (RIC) Transplant

Transplantation from a related donor for CML patients has, until recently, been limited to younger patients without significant co-existing health problems.

Reduced intensity conditioning (RIC) transplant is a newer technique that focuses on milder conditioning treatment that is better tolerated by older patients, up to the age of 65, or by patients with other medical problems. However, RIC-transplant may still result in serious and/or fatal graft-versus-host disease and infection.

The procedure is currently being evaluated in a research study.

Useful Resources

The following web sites may provide further helpful information:

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