Leukemias

Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a slow-growing cancer of the bone marrow and blood. It develops when a genetic change mutates or damages early (immature) myeloid cells, which are the cells that become white blood cells (other than lymphocytes), red blood cells or cells that make platelets.

This genetic change takes place because of translocation, which is when a piece of chromosome breaks off and attaches to another chromosome. The new chromosome, known as the Philadelphia chromosome, is in the leukemia cells of almost all people with CML. The translocation causes the formation of an abnormal fusion of two genes, BCR and ABL. The BCR-ABL gene fusion produces the BCR-ABL protein. This protein, which is a tyrosine kinase (an enzyme), helps CML cells grow and multiply at a much faster rate than normal white blood cells.

Classifying CML

The World Health Organization (WHO) classification system is used to classify CML into a chronic phase, accelerated phase and blast crisis phase (see Table 2). This helps doctors determine the best treatment and prognosis (predicted outcome after treatment).

In most cases, CML is diagnosed in the chronic phase. The progression of CML in the chronic phase is slow, and it may be several months or years before the next phase is reached. The response to treatment is typically better when treatment begins with CML in the chronic phase. The most advanced and aggressive phase is the blast crisis phase.

Treating CML

Targeted therapy is the main treatment for chronic phase CML. Targeted therapy that is taken orally (in pill form) is almost always the first line of treatment (meaning the first treatment given) for chronic phase CML. The more advanced stages of CML will usually respond temporarily but quickly require additional treatment; however, when caught in the chronic phase, some patients can receive targeted therapy and remain in remission for many years.

The BCR-ABL tyrosine kinase protein that helps CML cells grow can be blocked by a tyrosine kinase inhibitor (TKI). Resistance to this type of targeted therapy eventually develops in most patients; when that happens, several other TKIs are available that may work where others have failed. The response to the TKI therapy (complete response, partial response or no response) can be monitored by a blood test.

Chemotherapy is an option for treatment and is used especially for CML that does not respond to targeted therapy. It may also be used to treat CML that has not improved after treatment with TKIs.

Stem cell transplantation in the form of an allogeneic stem cell transplant may be an option, especially when disease is in the accelerated or blast phase. Allogeneic stem cell recipients may also receive a donor lymphocyte infusion from the original allogeneic blood stem cell donor to boost the attack on leukemia cells. A donor lymphocyte infusion is used to kill the remaining CML cells that have not gone away completely or have come back following the stem cell transplant.

Immunotherapy may be a treatment option, although it is not typically used as the first treatment for this disease. Cytokine immunotherapy is known as nonspecific immune stimulation and aids in immune cell communication. It plays a big role in the full activation of an immune response. It works by introducing large amounts of the laboratory-made cytokines to the immune system to promote specific immune responses. For CML, the most commonly used type boosts the ability of certain immune cells to attack cancer cells.

Clinical trials may be an option to consider.

Relapsed Or Resistant CML

The goal of CML treatment is to reach remission, which occurs when leukemia is not detected in the body and there are no symptoms. However, remission may be temporary or permanent. When CML returns, it is relapsed CML. Sometimes, the leukemia does not respond to treatment or stops responding. This is called resistant CML. Your doctor may try targeted therapy or consider a clinical trial with an eventual goal of inducing another remission and undergoing an allogeneic stem cell transplantation.

 

Drug Therapies for CML as of 10/16/20
azacitidine (Vidaza)
bosutinib (Bosulif)
busulfan (Busulfex, Myleran)
cyclophosphamide
cytarabine
dasatinib (Sprycel)
hydroxyurea (Hydrea)
imatinib mesylate (Gleevec)
nilotinib (Tasigna)
ponatinib (Iclusig)
Some Possible Combinations
busulfan (Busulfex) with cyclophosphamide

 

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