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Understanding CML and Its Treatment


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Chronic myelogenous leukemia, or CML, is one of four main types of leukemia. CML starts with a change to a single stem cell. Both children and adults can get CML, but most people with CML are adults. It is estimated that approximately 24,800 people in the United States are living with CML. Three new CML drugs (Gleevec®, Sprycel®, and Tasigna ®) have been approved since 2001. Other new treatments are being studied in clinical trials. Progress toward a cure is under way, and the number of people with CML who are living well today is growing.

People with CML have what is called the Philadelphia Chromosome (Ph chromosome). The Ph chromosome is made when a piece of chromosome 22 breaks off and attaches to the end of chromosome 9. A piece of chromosome 9 also breaks off and attaches to the end of chromosome 22. The break on chromosome 9 involves a gene called Abl. The break on chromosome 22 involves a gene called Bcr. The Bcr and Abl genes combine to make the CML-causing gene called the Bcr-Abl cancer gene.

Phases of CML
There are three phases of CML: the chronic phase, the accelerated phase, and the blast crisis phase.

Chronic Phase CML
Most people are in the chronic phase of the disease when their CML is diagnosed. In this phase, CML symptoms are milder. White cells can still fight infection. Once people in the chronic phase are treated, they can go back to their usual activities.

Accelerated Phase CML
In the accelerated phase, a person may develop anemia, the number of white cells may go up or down, or the number of platelets may drop. The number of blast cells may increase, and the spleen may swell. People with accelerated-phase CML may feel ill.

Blast Crisis Phase CML
People with blast crisis phase CML have an increased number of blast cells in the marrow and blood. The number of red cells and platelets drops. They may have infections or bleeding. They may also feel tired and have shortness of breath, stomach pain, or bone pain.

Progress toward a cure is under way, and the number of people with CML who are living well today is growing.

Goals of CML Therapy
In the chronic phase of CML, the goals of treatment are to return the levels of blood cells to normal and to kill all cells that have the Bcr-Abl cancer gene. In the accelerated phase or blast phase, the goal of CML treatment is to kill all cells that have the Bcr-Abl cancer gene or to return the disease to the chronic phase.

Oral CML Therapy
In chronic phase CML, treatment usually returns the level of blood cells to normal. The spleen returns to its normal size. Most people don’t have infections or unusual bleeding.

Many people with CML begin treatment with a drug called Gleevec, which has been FDA-approved since 2001. Gleevec controls chronic phase CML for most people as long as they continue to take the drug. People who do not respond to the usual dose of Gleevec may respond to a higher dose.

Recently, the FDA approved Tasigna (nilotinib) for the treatment of adults who are newly diagnosed with chronic phase CML. The FDA originally approved Tasigna in October 2007 to treat chronic and accelerated phases of CML in adults with disease that is resistant or intolerant to prior CML therapy.

The FDA also recently approved Sprycel (dasatinib) for the treatment of adults who are newly diagnosed with chronic phase CML. Sprycel was first approved in 2006 to treat adults in all phases of CML with resistance or intolerance to prior CML therapy. All three drugs, Gleevec, Sprycel, and Tasigna, are taken by mouth.

Some people with CML have very high white cell counts at the time of diagnosis.

Most people being treated for chronic phase CML can go about their day-to-day activities. With drug treatment, most people are symptom free for very long periods (called a remission). However, people are not cured of CML with drug treatment. They are checked carefully for any signs that CML is returning (called a relapse). They will need regular health check-ups, including blood tests. From time to time, a bone marrow test will be needed.

Accelerated Phase or Blast Crisis Phase Treatment
The goal in treating accelerated or blast crisis phase CML is to kill all cells that contain the Bcr-Abl gene or to return the person’s disease to the chronic phase.

Gleevec, Tasigna, or Sprycel may be effective treatments for people who have accelerated or blast crisis phase CML. Other drugs – such as interferon, busulfan (Myleran®), cytarabine (Cytosar-U®), and hydroxyurea (Hydrea®) – may be used with those CML oral drugs.

Some people with CML have very high white cell counts at the time of diagnosis. This can reduce blood flow to the brain, lungs, eyes, and other parts of the body. Hydrea may be used to decrease the white cell count. After the white cell count drops, oral drug therapy can be started. People also can have white cells removed by a special machine. This process is called leukapheresis. Leukapheresis can be used for women diagnosed with CML in the first months of pregnancy, when drug therapy may be harmful to the unborn baby.

Side Effects of Oral CML Therapy
Many treatment side effects go away or become less noticeable over time. Most can be handled without the need to stop the drug. Talk to your doctor about the possible side effects and long-term effects of your treatment.

Common side effects of Gleevec may include swelling from too much fluid in the body, puffiness around the eyes, nausea, vomiting, muscle cramps, diarrhea, and rash. Gleevec may also cause loss of bone minerals. Your doctor will check for these possible side effects.

Common side effects of Sprycel may include too few red cells, white cells, and/or platelets; too much fluid in the chest; too much fluid in other tissues (edema); diarrhea; headache; low calcium levels in the blood; and slight changes in liver function.

Common side effects of Tasigna may include too few white cells and/or platelets, changes in liver enzymes, changes in pancreatic enzymes, nausea, constipation, diarrhea, itching, and rash.

QT Prolongation
A possible side effect of Gleevec, Sprycel, and Tasigna is a heart rhythm condition called QT prolongation. Your doctor will monitor you for this condition as needed. Some other medications can cause QT prolongation. Your doctor will give you a list of medications to avoid.

Stem Cell Transplantation
Stem Cell Transplantation is another important treatment for certain people with CML. Allogeneic stem cell transplantation is the only curative treatment for CML. It is a treatment to restore a person’s marrow. The transplanted stem cells go from the person’s blood to his or her marrow. The cells start a new supply of red cells, white cells, and platelets. The person needs to have a “matched” stem cell donor for the transplant. The donor can be a sibling or another person with stem cells that “match” the stem cells of the person receiving the transplant.

About 7 out of 10 people who have an allogeneic transplant are cured of their CML. But this procedure has a high risk of serious complications. This treatment is most successful in younger people. It may be considered for people up to about 60 years of age who have a matched donor and who do not have a good response to oral drug treatment. The decision to do a transplant for a person with CML depends on the person’s age, his or her overall health, how well the donor cells and the recipient cells match, and the degree of the person’s response to oral drug therapy.

If a stem cell transplant is suggested for you, your doctor will discuss the benefits versus the risks of having this treatment. Doctors are studying a type of stem cell transplant called a reduced-intensity transplant (nonmyeloablative stem cell transplant). It may be helpful for older people who are not eligible for allogeneic stem cell transplantation.

Donor Lymphocyte Infusion
People with CML whose disease returns after an allogeneic stem cell transplant may be treated with Gleevec, Sprycel, Tasigna, or other CML drugs. Another treatment choice is a second transplant. Or people may be treated with a donor lymphocyte infusion, an infusion of white cells (called lymphocytes) from the original stem cell donor.

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Reprinted with permission from the Leukemia & Lymphoma Society,, copyright © 2011.

Coping® does not endorse or recommend any particular treatment protocol for readers, and this article does not necessarily include information on all available treatments. Articles are written to enlighten and motivate readers to discuss the issues with their physicians. Coping believes readers should determine the best treatment protocol based on physicians’ recommendations and their own needs, assessments and desires.