Chronic Myeloid Leukemia

I thought i would inform yall of what CML is and how it works.

Understanding CML
About 4,570 people in the United States will learn they have chronic myelogenous leukemia (CML) in 2007 in the United States. About 21,501 people in the United States are living with CML (SEER, National Cancer Institute, 2007). The progress that has been made in treating CML gives patients more hope than ever before.
Leukemia is a type of cancer. There are four main types of leukemia. CML is one of the four types. CML starts with a change to a single stem cell. Both children and adults can get CML, but most CML patients are adults.
CML patients have what is called the "Philadelphia Chromosome" (Ph chromosome). Every cell with a nucleus has chromosomes. The Ph chromosome is made as the result of a piece of chromosome 22 breaking off. With CML, there is a switch in pieces of chromosome 9 and 22. The break on chromosome 9 involves a gene called "ABL." The break on chromosome 22 involves a gene called "BCR."
A piece of chromosome 9 attaches to the end of chromosome 22 and the BCR-ABL cancer gene is made. The BCR-ABL cancer gene gives the cell instructions to make a protein that leads to CML.

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Causes and Risk Factors
Doctors are working to understand the changes that lead to the Ph chromosome and the BCR-ABL cancer gene. Some risk factors that may cause these changes are:
Very high levels of radiation (such as atomic bomb survivors were exposed to in World War II)
High dose radiation therapy used to treat other cancers.
Most people with CML do not have these risk factors. Many people with these risk factors do not get CML.There is no link between dental or medical x-rays and increased risk of CML. You cannot catch CML from someone else.
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Signs and Symptoms
CML signs and symptoms tend to develop slowly. Some patients learn about their CML after a routine blood test given during a check up.
Some changes that a person with CML may have are:
Tiredness
Shorteness of breath doing activities
Pale-looking skin
Enlarged spleen
Night sweats
Weight loss
These signs and symptoms for CML are common to other illnesses.
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Diagnosis
Lab tests are used to make a CML diagnosis. They are also used to check a patient's response to treatment.
Blood and Bone Marrow Tests Blood and bone marrow tests are done to look for leukemia cells to find out if a person has CML. In CML, the white cell count increases, often to very high levels. Platelet counts may also be high. Levels of hemoglobin go down.
A CML diagnosis is usually clear from an exam of blood cells. A bone marrow aspirate and a bone marrow biopsy are two tests that are done to look at the marrow cells for changes that can't be seen in cells in the blood. These tests may help the doctor to choose the best treatment for the patient. The tests also help the doctor to follow the effects of therapy.
Cytogenetic Analysis Cytogenetic analysis is a lab test to examine the chromosomes of the leukemia cells. This test helps the doctor to find out if the patient's type of leukemia is CML.
FISH is a lab test used to measure the patient's percent of CML cells.
PCR is a very sensitive test that is used when there are no CML cells found by FISH.
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Phases of CML
CML can have three phases:
The chronic phase
The accelerated phase
The blast crisis phase
Most patients are in the chronic phase of the disease when their CML is found. During this phase, CML symptoms are less intense. White cells can still fight infection. Once patients in the chronic phase are treated, red cells and platelets can do their jobs. Most patients can go back to their ususal activites.
In the accelerated phase, the patient may develop anemia, the number of white cells may go up or down. The number of platelets may drop.
The number of blast cells increases. The spleen may swell and the patient may feel ill.
During the blast crisis phase:
The number of blast cells grows in the marrow and blood
The number of red cells and platelets drops
The patient may have infections
The patient may be tired and have shortness of breath, stomach pain, bone pain or bleeding.
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Treatment
Some CML patients may want to get a second medical opinion. It is important to get treatment in a center where doctors are experienced in the care of patients with CML.
Chronic Phase Treatment - Drug Therapy The goal of treating chronic phase CML is to bring the level of blood cells back to normal and to get rid of all cells with the BCR-ABL cancer gene.
In chronic phase CML, treatment usually returns the level of blood cells to normal. The spleen shrinks towards normal size. Most patients don't have infections or unusual bleeding.
CML patients begin treatment with a drug called Gleevec. This drug has been FDA-approved since 2001. For some patients, Gleevec keeps CML under control for as long as they take the drug. Some patients taking Gleevec have strong side effects or the drug does not work for them. Patients who do not respond to the usual dose of Gleevec may do better with a higher dose.
For other patients, there are two newer drugs called Sprycel and Tasigna. These drugs also block the BCR-ABL cancer gene. They work in a different way than Gleevec. All three of these drugs are taken by mouth.
Most patients being treated for chronic phase CML can go about thier day-to-day activities. With drug treatment most patients are symptom free for very long periods (called a remission).
However, patients 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 patient will need a bone marrow test.
CML is likely to return if drug treatment is stopped. The disease may also return if the drug treatment stops working (called drug resistance). There are other drug treatments patients who develop resistance to a particular drug.
Leukapheresis Some patients have very high white cell counts at the time the doctor discovers their CML. This can reduce blood flow to the brain, lungs, eyes and other places in the body. Patients can have white cells removed by a machine. The process is called leukapheresis. A drug called hydroxyurea (Hydrea®) may also be used to decrease the white cell count. After the white cell count drops, Gleevec can be started. Leukapheresis can be used for patients diagnosed with CML in the first months of pregnancy, when drug therapy may be harmful to the unborn baby.
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 patient's disease to the chronic phase. Gleevec, and for certain patients, Sprycel, are important treatments for accelerated or blast crisis phase patients. Stem cell transplantation is another important treatment for certain patients.
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Treatment Response
Measuring treatment response is very important. The doctor may use the terms hematologic, cytogenetic or molecular remission (response). Blood tests can be used to see if a patient has a complete hematologic response (red cell, white cell and platelet counts are normal or near normal).
A blood test or a bone marrow biopsy may be used to do FISH and/or PCR testing.
FISH is used to measure the patient's cytogenetic response (the percent of CML cells that remain). PCR is used to measure the patient's molecular response (the extent to which the BCR-ABL gene is decreased). Most CML patients in chronic phase CML have a complete hematologic response with Gleevec. Many of these patients go on to have a complete cytogenetic response. They may also have a partial or complete molecular response. There are other treatments for patients who do not get a good response with Gleevec.
Side Effects of Gleevec and Sprycel Treatment Many treatment side effects go away or become less noticeable over time. Gleevec may cause some side effects. Most can be handled without the need to stop the drug. These more common effects include:
Swelling from too much fluid in the body
Puffiness around the eyes
Nausea
Vomiting
Muscle cramps
Diarrhea
Rash
Bone and/or joint pain
Too few white cells and/or platelets.
Gleevec may also cause loss of bone minerals. In rare cases, the drug may affect the heart. The doctor will check patients for these possible side effects.
Side effects of Sprycel may include:
Too few white cells and/or platelets
Too much fluid in the chest
Diarrhea
Headache
Low calcium levels in the blood
Slight changes in liver function.
Doctors are studying how CML drug treatment affects pregnancy. They want to learn if Gleevec, Sprycel and other CML drugs cause miscarriage and/or birth defects. In the meantime, most doctors advise women in treatment for CML to use birth control. Speak to your doctor for more information.
The Society's free booklet, Understanding Drug Therapy and Managing Side Effects, has more information about drugs and side effects.
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Stem Cell Transplantation
A stem cell transplant (sometimes called a bone marrow transplant) is used for some patients with CML.
Donated stem cells (allogeneic stem cell transplant) or the patient's own stem cells (autologous stem cell infusion) are injected into the patient's blood after chemotherapy ends.
The Society's free booklet, Blood and Marrow Stem Cell Transplantation, has more details on this topic.
Allogeneic stem cell transplantation can be a high-risk treatment. It is the only treatment that can cure CML. Gleevec or other drugs can control CML in many patients for a long time. The decision to do a transplant for CML patients depends on:
Patient age
Overall health
How well the donor cells and patient cells "match"
The patient's response to drug therapy (the degree of cytogenetic response and molecular response).
The decision also depends on the patient's understanding of the benefits and risks of the transplant. If the doctor thinks a patient might benefit from a transplant, he or she will talk about these factors with the patient. This procedure is most successful in younger patients. Patients up to about 60 years of age who have a matched donor may be considered.
Doctors are studying a type of stem cell transplant called a nonmyeloablative stem cell transplant or mini transplant. It may be helpful for older patients.
Donor Lymphocyte Infusion CML patients whose disease returns after an allogeneic stem cell transplant (called a relapse) may be treated with Gleevec, Spycel or another CML drug. Another treatment choice is a second transplant. Or patients may be treated with a donor lymphocyte infusion (an infusion of white cells called lymphocytes from the original stem cell donor).
Many CML patients cannot have an allogeneic stem cell transplant. Doctors are studying the use of a patient's own stem cells in these cases. This is called an autologous stem cell infusion. During the chronic phase of CML, stem cells are taken from the patient's blood or marrow and frozen. The stored stem cells are infused back into the patient's blood after treatment with chemotherapy ends.These stem cells may help the body make healthy blood cells after treatment.
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Clinical Trials
Clinical trials are used to study new drugs, new treatments or new uses for approved drugs or treatments. Doctors are studying other drugs for CML. Questions to be explored include:
Would Tasigna be useful in patients who cannot take Gleevec because of severe side effects or poor response?
Would Sprycel would work as well or better than Gleevec as a first treatment of chronic phase CML?
Would using more than one drug at the same time is more helpful than using a single drug?
Would drugs, such as VX-680, help CML patients in the blast crisis phase of CML who have not responded to other treatment?
Another goal of research for CML is to use vaccine therapy. This type of vaccine would not prevent the disease. Instead, the vaccine would increase the immune system's attack against remaining CML cells. The goal is to keep the disease in remission for a longer time. Three CML vaccines under study, AG-858, CMLVAX and PR1 are described in the Society's free publication, Vaccine Therapy Facts.
Doctors are studying a type of stem cell transplant, called a nonmyeloablative stem cell transplant (or "mini-transplant"). Scientists are studying using umbilical cord blood as a source of stem cells for transplants in children and adults. This provides another possible source of matched, unrelated stem cells for patients without a matched, related stem cell donor. Results from cord blood stem cell transplants are promising.
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Related Disorders
There are other types of CML that do not involve the BCR-ABL cancer gene. These other, less common types of CML are called chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia and chronic neutrophilic leukemia.
For more information on these types of CML, see the Society's free fact sheet, The Chronic Myelomonocytic Leukemias (CMML).
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Talking to the Doctor
It may be helpful to write down questions to ask your doctor. Then you can write down your doctor's answers and review them later. You may want to bring a family member or friend with you to the doctor. This person can listen, take notes and offer support. Some patients record information and listen to it at home.
Questions to Ask Your Doctor
Find Support
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Get More Information
Further details of treatment and supportive care and the beneficial and adverse effects of treatment may be obtained from The Leukemia & Lymphoma Society's CMLLinks Web site and from our free publications CML: A Guide for Patients and Caregivers and Chronic Myelogenous Leukemia.
The Leukemia & Lymphoma Society offers ongoing education programs featuring leading leukemia specialists discussing the latest issues in the diagnosis and treatment of leukemia. Follow CML News Briefs on the CML Links home page and visit the Teleconferences page of the CMLLinks Web site to find out about upcoming and archived programs. These programs are offered at no charge.
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Contact Us
The Leukemia & Lymphoma Society 1311 Mamaroneck Ave. White Plains, NY 10605
or call the Information Resource Center at (800) 955-4572.
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Helpful Links
CML Medical Monitor Visit this online health tool and educational resource for people living with CML. Features a treatment progress tracker to help you monitor your responses to therapies. National Cancer Institute This site offers comprehensive information about cancers and the diagnosis procedures.
Medicine Online This site offers information about diagnosis and treatment (including immunotherapy), with pages written by several physicians. Go to "cancer links/leukemia/current".