Leukemia

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Is Leukemia a Cancer?

Cancer is a process of uncontrolled abnormal cell growth and development. Under normal circumstances, cells are formed, mature, carry out their intended function, and then die. New cells are constantly regenerated in the body to replace those cells and to maintain normal cellular function.

Cancer represents the disturbance of this process, which can occur in several ways.

Cells may grow and reproduce in a disorganized and out-of-control fashion. Cells may fail to develop properly, so they will not function normally. Cells may fail to die normally. One or a combination of these processes may occur when cells become cancerous.

Leukemia is a cancer of blood-forming cells in the bone marrow. These deranged, immature cells accumulate in the blood and within organs of the body. They are not able to carry out the normal functions of blood cells.

Normal blood contains white blood cells, red blood cells, and platelets. All three types of blood elements develop from one immature cell type, called blood/marrow stem cells, in a process called hematopoiesis.

  • These stem cells divide and develop into a more developed, but still immature precursor, called a blast, which then develops through several more stages, into a mature blood cell.
  • This process takes place in the bone marrow, which is the soft spongy material found in the center of most bones.

Each type of blood element has its own different and essential function in the body.

  • White blood cells (leukocytes) are part of the immune system and help fight a variety of infections. They also help in the healing of wounds, cuts, and sores.
  • Red blood cells (erythrocytes) contain hemoglobin, which carries oxygen to, and removes carbon dioxide from, the cells throughout the various organs of the body.
  • Platelets, along with certain plasma proteins, help form clots once blood vessels are damaged or cut.

The first step in the process of stem cell maturation is differentiation into two groups: the myeloid stem cell line and the lymphoid stem cell line.

  • The myeloid stem cells, or lineage, develop into red blood cells, platelets, and certain types of white blood cells (granulocytes or monocytes).
  • The lymphoid stem cells, or lineage, develop into another type of white blood cell (lymphocytes).
  • Either lineage can be affected by leukemia. Leukemias that affect the myeloid lineage are called myelocytic (also myelogenous, myeloblastic, or nonlymphocytic) leukemias. Leukemias that affect the lymphoid lineage are called lymphocytic (also lymphoblastic or lymphogenous) leukemias.

Each of the two major types of leukemia, myelogenous and lymphocytic, include both acute and chronic forms.

  • Acute leukemia essentially refers to a disorder of rapid onset. In the acute myelocytic leukemias, the abnormal cells grow rapidly and do not mature. Most of these immature cells tend to die rapidly. In the acute lymphocytic leukemias, growth is not as rapid as that of the myelocytic cells. Rather, the cells tend to accumulate. Common to both types of leukemia is their inability to carry out the functions of healthy white blood cells. Untreated, death occurs rapidly, often within weeks or a few months.
  • In the chronic leukemias, the onset tends to be slow, and the cells generally mature abnormally and often accumulate in various organs, often over long intervals. Their ability to fight infections and assist in repairing injured tissues is impaired. However, unlike the acute forms of leukemia, untreated, these disorders may persist without resulting in death for many months in chronic myelogenous leukemia, or, as in the case of chronic lymphocytic leukemia, many years. A distinctive feature of the chronic myelocytic type is its virtually invariable conversion, if untreated, to a more rapidly fulminating acute type in what is referred to as a blast crisis, leading to rapid death.

What Kind of Leukemia Is There?

In summary, the four main types of leukemia are as follows:

Less common types include hairy cell leukemia and human T-cell leukemia.

Leukemia affects people of all ages. Approximately 85% of leukemias in children are of the acute type.

  • Acute lymphocytic leukemia (ALL) affects both children and adults but is more common in children. It accounts for 65% of the acute leukemias in children.
  • Chronic lymphocytic leukemia (CLL) is essentially an adult disorder and is almost twice as common as chronic myelocytic leukemia.
  • Acute myelocytic leukemia (AML) is the most common acute leukemia in adults.
  • Chronic myelocytic leukemia (CML) is far more common in adults than in children.

As leukemic cells grow and eventually outnumber normal cells, the following events occur:

  • The normal blood cells are disabled, resulting in conditions such as frequent infections, bleeding problems, poor healing of small cuts or sores, and anemia (low red blood cell count).
  • The leukemia cells may collect in certain parts of the body, causing pain, swelling, and other problems.
  • Identifying the type of leukemia is important, since this determines which treatment is given.

Leukemia of all forms is presently estimated to be diagnosed in about 54,000 people in the U.S. in 2015 (ACS - Facts and Figures 2015).

  • In adults, the acute leukemias occur in those of all ages, whereas the chronic varieties, particularly CLL, tend to occur in people older than 40 years.
  • Leukemia is one of the most common cancers of children.
  • Leukemia is more common in people of European descent than in African Americans, Hispanic Americans, Asian Americans, or Native Americans.

Survival rates in leukemia have risen dramatically in the last 40 years with improvements in diagnosis and treatment.

  • In 1960, the overall 5-year survival rate for all leukemias was about 14%. It is now about 55%.
  • The highest survival rates occur in children with the so-called "common" ALL type.

What Causes Leukemia?

The exact cause of leukemia is unknown.

  • As with other cancers, smoking is considered a risk factor for leukemia, but many people who develop leukemia have never smoked, and many people who smoke never develop leukemia.
  • Long-term exposure to chemicals such as benzene or formaldehyde, typically in the workplace, is considered a risk factor for leukemia, but this accounts for relatively few cases of the disease.
  • Prolonged exposure to radiation is a risk factor, although this accounts for relatively few cases of leukemia. Doses of radiation used for diagnostic imaging such as X-rays and CT scans are nowhere near as prolonged or high as the doses needed to cause leukemia.

Other risk factors for leukemia include the following:

  • Previous chemotherapy: Certain types of chemotherapy, particularly certain of the alkylating agents and topoisomerase inhibitors, used to treat various types of cancers, are linked to development of leukemia later. It is likely that radiation treatment adds to the risk of leukemia associated with certain chemotherapy drugs.
  • Human T-cell leukemia virus 1 (HTLV-1): Infection with this virus is linked to human T-cell leukemia.
  • Myelodysplastic syndromes: This unusual group of blood disorders (formerly referred to as "preleukemia") is characterized by abnormal blood cell development and a highly increased risk of leukemia.
  • Down syndrome and other genetic diseases: Some diseases caused by abnormal chromosomes may increase risk for leukemia.
  • Family history: Having a first-degree relative (parent, brother, sister, or child) who has chronic lymphocytic leukemia increases one’s risk of having the disease by as much as four times that of someone who does not have an affected relative.
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What Are Signs and Symptoms of Leukemia?

Symptoms usually develop fairly quickly in acute leukemias. Most cases of acute leukemia are diagnosed when the person visits his or her healthcare professional after becoming ill. Symptoms develop gradually in chronic leukemias and are generally not as severe as in acute leukemias. About 20% of people with chronic leukemia do not have symptoms at the time their disease is diagnosed and it is only a blood test which leads to the diagonsis.

Some symptoms of leukemia are due to deficiencies of normal blood cells. Others are due to collections of leukemia cells in tissues and organs. Leukemia cells can collect in many different parts of the body, such as the testicles, brain, lymph nodes, liver, spleen, digestive tract, kidneys, lungs, eyes, and skin -- in effect, virtually every tissue site.

The following symptoms of leukemia are common to all acute and some chronic types:

Collection of leukemia cells in certain parts of the body may cause the following symptoms:

It is important to emphasize that the symptoms of leukemia are nonspecific. This means that they are not unique to leukemia but are common to a number of diseases and conditions. Only a medical professional is able to distinguish leukemia from the other conditions that cause similar symptoms.

When to See a Doctor

See a health care professional promptly if any of the following symptoms appear:

  • Unexplained fevers
  • Night sweats
  • Unexplained weight loss
  • Bleeding or bruising easily
  • Swelling in the neck, under the arm, or in the groin
  • Persistent pain in the abdomen, back, or bony areas
  • Persistent headache, confusion, balance problems, or difficulty concentrating
  • Sores or minor infections that fail to heal
  • Persistent blurred vision

Leukemia Diagnosis

Because the symptoms of leukemia are nonspecific and the causes are not clearly defined, one's health care professional will carry out a complete history and physical examination and any appropriate tests in order to identify the underlying cause.

  • The health care professional will ask many questions about symptoms, current medical situations, medications, medical and surgical history, family history, work history, and habits and lifestyle.
  • The physical examination includes a thorough evaluation of all symptoms, not merely lymph nodes and/or possible enlargements of the liver and spleen.

Blood tests: Blood is drawn from a vein in order to check the blood cell counts. In most cases of leukemia, the white blood cell count is abnormal - either very low, or more commonly, very high (although it is not uncommon for the white cell count to be normal in many of the childhood acute lymphocytic leukemias) and the platelet and red cell counts are low. This makes the health care professional consider leukemia as the diagnosis. Other tests are performed to check liver and kidney functions and the possible presence of leukemic cells in the spinal fluid.

Biopsy: Because other conditions may give rise to atypical white cell counts, the only way to confirm the diagnosis of leukemia is via an aspirate and biopsy of the bone marrow.

  • Biopsy means to take a small sample of the relevant tissue to check for abnormal cells. In leukemia, a biopsy of the bone marrow must be taken and examined.
  • This procedure is usually performed in the medical office, usually by a specialist trained in the treatment of blood disorders, that is, a hematologist or a hematologist-oncologist. The procedure is brief (less than a few minutes) and preceded by a local injection for anesthesia.
  • Samples of both liquid (aspirate) and solid bone marrow (biopsy) are taken, usually from a hip bone.
  • The bone marrow is examined under a microscope, where the presence of leukemic cells confirms the suspected diagnosis.

Genetic and molecular studies: The detailed subtypes of the structures of the leukemia cells as well as the chromosomes of the abnormal cells are examined to look for irregularities. This helps in classifying the various types of leukemia.

Lumbar puncture (spinal tap): Because the collection of leukemia cells in the central nervous system can affect essential mental processes and processes controlled by the nervous system, it is extremely important to know whether the fluid surrounding the brain and spinal cord (cerebrospinal fluid) is affected.

  • This procedure is referred to as a lumbar puncture or spinal tap and is usually carried out by the blood specialist in the office. After the procedure, the person needs to lie flat for 1 to 2 hours.
  • A small amount of the fluid is removed from the area around the spinal cord by inserting a hollow needle in the back at around the waist level. The needle is inserted in between the bones in the spine following a small injection into the skin over the injection site in order to minimize discomfort.
  • The fluid is examined for the presence of leukemia cells.

Lymph node excision: If the lymph nodes are enlarged, a node may require a biopsy if the bone marrow is difficult to interpret for some obscure reason. This is exceedingly uncommon.

Chest X-ray: A chest X-ray is frequently taken to look for signs of infection or lymph node involvement by leukemia.

Staging

Staging is the way cancers are classified. Staging indicates the size or extent of spread of the cancer, the degree to which other parts of the body are affected, and other important details. In general, leukemias are classified rather than staged in order to determine the most appropriate therapy.

All leukemias are classified according to their genotypes, or their unique chromosomal arrangements, which also enables the physicians to determine risk factors. Today testing of surface markers on leukemia cells by flow cytometry also helps to classify the type of leukemia present.

In addiction, chronic myelogenous leukemia is classified by phase. The three phases are chronic phase, accelerated phase, and blast phase (or "blast crisis") and are defined by the number of blasts (immature leukemia cells) in the blood and bone marrow.

Chronic lymphocytic leukemia is classified by two different staging systems, both based on the types of blood cells and the parts of the body affected by the leukemia.

Leukemia Treatment

Specialists who treat blood disorders and other kinds of cancer are either hematologists or hematologist-oncologists. These specialists treat leukemia.

  • Children are usually treated by a specialist in childhood cancers (pediatric hematologist or hematologist-oncologist).
  • On other occasions, more than one opinion may be sought by the patient or by the referring primary care physician. In acute leukemia, the disease can change swiftly and time for further opinions may be limited. In chronic leukemia, there is often time, unless severe symptoms are present at the time of diagnosis.
  • Leukemia patients often find it helpful to take a family member or close friend along to these consultations in order to take notes and assist in remembering some of the points of the discussion.
  • Most patients are treated in the offices of hematologist-oncologists, or in major medical centers with state-of-the-art cancer treatment programs.

Once the patient has had the first encounter with the specialist, he or she will have ample opportunity to ask questions and discuss treatment options. The advantages and disadvantages of various treatment options are thoroughly discussed.

  • Leukemia treatment depends almost exclusively on the type. Modifying factors may be age, overall health, and prior therapy. Treatment is almost always carried out as part of carefully controlled multi-center programs so that information from many different areas may be constantly analyzed and altered if the results appear to necessitate changes. The patient is always kept abreast of ongoing treatment activities and changes in the treatment plan.
  • Treatment commences only if the patient or the patient's guardian concurs.
  • In addition to the blood specialist, the patient's medical care team usually includes a specialist nurse or physician assistant, social worker (and for children, child-life worker), and sometimes a member of the clergy, all of whom play major roles in furthering well being.

Leukemia Medical Treatment

Leukemia treatment falls into two categories -- treatment to fight the cancer and treatment to relieve the symptoms of the disease and the side effects of the treatment (supportive care).

The most widely used antileukemic treatment is chemotherapy, that is, the use of powerful drugs to kill leukemia cells.

  • Treatment usually involves combinations of chemotherapy.
  • Depending on the medication, therapy may be administered by vein or by mouth.
  • In some cases, chemotherapy can be given at the doctor's office or some may be taken at home; in other cases, the patient may have to stay in a hospital. This depends on which agents the patient is receiving along with his or her overall condition (sometimes measured in terms of "performance status").

Many people with leukemia have a semi-permanent intravenous (IV) line placed in the arm, or more commonly today, the upper chest, near the shoulder.

  • A thin, plastic tube called a catheter is passed through the skin of the chest and inserted into a large vein. It is held in place, usually for the planned duration or therapy, with a few stitches, which makes it possible to use the same vein on numerous occasions without worry about the intravenous line being pulled out. The line is often burrowed under the skin.

People who have leukemia in their cerebrospinal fluid, or who are at high risk of having leukemic cells migrate to the spinal fluid, receive chemotherapy directly into the cerebrospinal canal. This is known as intrathecal chemotherapy.

  • Intrathecal chemotherapy is necessary because drugs given via IV do not sufficiently penetrate into the cerebrospinal fluid or brain and, thus, cannot kill leukemia cells there. Insufficient penetration of drugs into the cerebrospinal fluid results in uncontrolled growth of leukemic cells in the cerebrospinal fluid. Sometimes the therapy is inserted into a sterile plastic and metal chamber placed in one of the larger fluid-filled areas of the brain, a ventricle. The sac is known as an Ommaya reservoir, so named after its developer.
  • The reservoir stays in place for the duration of the treatment.

More Leukemia Medical Treatment

Chemotherapy kills cells or stops them from reproducing. Chemotherapy also kills rapidly growing healthy cells, accounting for many of the side effects of therapy.

  • The exact side effects depend on the particular agent or agents administered to the patient, and the severity of side effects depends on the doses given and the patient's tolerance.
  • Chemotherapy has its most severe effects on the bone marrow, the hair follicles, and the digestive system (from the mouth to the anus). These are the areas of the body where cells reproduce and replace themselves most quickly. Occasionally, the fingernails and toenails may splinter, crack, develop deep ridges, or stop growing.
  • Common side effects of chemotherapy include nausea and vomiting, diarrhea, hair loss, and irritation of the esophagus (the tube through which food passes from the mouth to the stomach).
  • Because chemotherapy kills normal blood cells, it can have some of the same effects as the leukemia itself: infections, anemia, and bleeding problems. Therefore, treatment of a patient with leukemia may involve the use of antibiotics and other anti-infective agents, red blood cell and platelet transfusions, and periodic injections to help increase the production of healthy red blood cells.

Newer agents are being developed that target leukemia cells and only minimally affecting healthy cells. These agents are known as targeted therapy.

  • These agents greatly reduce the severity of side effects.
  • Imatinib (Gleevec), an agent used in the treatment of CML, is an example of such a targeted therapy drug.

Chemotherapy is usually given in cycles.

  • Each cycle consists of intensive treatment over several days followed by a few weeks without treatment for rest and recovery from side effects caused by the chemotherapy, particularly anemia and low white blood cells. The sequence is then repeated.
  • Chemotherapy regimens may be administered for two to six cycles, depending on the subtype of leukemia and risk factors involved.
  • In accordance with particular treatment regimens, bone marrow exams may be carried out prior to each cycle of chemotherapy. After completion of treatment, the patient is evaluated again to see the effect of the chemotherapy on the leukemia.

Hematologists and oncologists often refer to phases of chemotherapy. Only in certain types of leukemia are all three phases used.

  • Induction: The purpose of this first phase is to kill as many leukemia cells as possible and bring about a remission.
  • Consolidation: In this phase, the goal is to seek out and kill the residual leukemia cells not killed by induction. Often, these cells are not detectable, but they are assumed to be still present.
  • Maintenance: The third phase is used to keep numbers of leukemia cells low, that is, to keep the disease in remission. The doses of chemotherapy are not as high as in the first two phases. This phase can last as long as 2 years.

The fundamental goal of chemotherapy is to cure the patient. Cure means that blood tests and bone marrow biopsy again become normal and show no evidence of leukemia (the patient is siad to be in complete remission) and the leukemia does not come back (relapse) over time. Only time can determine whether a remission (with no evidence of disease) will lead to disease-free survival (cure). In effect, remission may be short-lived, thereby requiring administration of new, previously unseen therapy. Results of this approach, often referred to as second-line therapy, are rarely curative. Stem cell transplant, if available, has the best chance of a second-line therapy cure.

Targeted Therapy

In chronic myelogenous leukemia (CML) the majority of patients have a chromosomal abnormality called a Philadelphia chromosome – caused by a piece of one chromosome becoming attached to another. This abnormality results in the production of an abnormal protein in the CML cells which drive them to behave abnormally. Drugs called TKIs (tyrosine kinases inhibitors) have been developed which target the abnormalities in these cells and can result in remission of the disease. The first of these drugs was called Imatinib or Gleevec, and now there are several others used for imatinib refractory cases.

Biological drug therapy: This type of therapy uses biological drugs that act similarly to the body's natural immune system, such as monoclonal antibodies, interferon, or interleukins.

  • Biological therapy consists of proteins like those produced naturally by the body's immune system to promote the body's innate ability to fight cancer.
  • Some people with chronic lymphocytic leukemia or acute myelogenous leukemia receive a monoclonal antibody. This is an antibody specifically designed to fight their type of leukemia cells.

Radiation therapy: Radiation therapy is another treatment occasionally used in some types of leukemia.

  • A high-energy beam is targeted at an organ, such as the brain, bones, or spleen, where large numbers of leukemia cells have collected. The radiation kills these cells.
  • Radiation to the brain can have negative long-term effects on some people, especially children. It has been linked to learning or thinking problems later in life. For this reason, radiation to the brain is carefully calibrated and used only when absolutely required.

Stem cell transplantation: This is a treatment that allows use of very high doses of chemotherapy along with total body irradiation in order to kill the leukemic cells.

  • At the completion of potentially lethal, high doses of chemotherapy with or without whole-body radiation, the patient's immune system is totally depleted, and the patient is at high risk of developing serious life-threatening infections. Accordingly, these patients are treated in specially designed, sterile, air-filtered bone marrow or stem-cell transplant rooms.
  • Immediately upon completion of the high-dose therapy, stem cells from a healthy, complete blood cell matched donor, usually a sibling or less commonly an unrelated donor, are given a transfusion into a vein. The cell so transplanted will then migrate to the marrow where they engraft, or grow and multiply before entering the circulation, a process that may take 2 to 3 weeks to be completed. On rare occasions, when a donor is not available, one's own marrow cells, usually pretreated in order to remove residual, but otherwise unseen, leukemic cells, are infused. This approach is far less successful than the use of matched donor cells.
  • If a patient receives stem cells from a matched donor, the type of stem cell transplant is called allogeneic. If the patient’s own stem cells are reintroduced back into the patient following high dose therapy, the transplant is called autologous. Marrow or stem cells from an identical twin given after high-dose therapy is referred to as a syngeneic transplant.

Leukemia Medications

Numerous chemotherapy and biological drug combinations may be prescribed by an oncologist. Which type and combination of therapy depends on many factors including the type and stage of leukemia, whether treating adult or childhood leukemia, ability to tolerate chemotherapy side effects, and if any previous treatment for the leukemia has occurred. Oncologists often work together regionally to decide which combination of chemotherapy and biological drugs are currently working best for their patients. Because of this, the drug combinations often vary and are able to change rapidly when improved results occur.

Leukemia Surgery

Surgery is generally not used to treat leukemia. Occasionally, a person with leukemia that has spread to the spleen has the spleen removed. This is usually done only if the spleen is so large that it is causing problems for nearby organs.

Leukemia Other Therapy

While alternative therapies, such as supplements, herbs, and body therapies, are not recommended as a replacement for medical treatment in leukemia, they may be considered complementary therapies.

The following therapies have proponents but no scientific evidence of unequivocally proven benefit:

Alternative or complementary therapies should be discussed with the treating specialist. These therapies are not offered in conjunction with chemotherapy for leukemia because of the lack of definitive data to support their use.

Leukemia Follow-up

After completion of treatment, the diagnostic studies are repeated to see how the treatment has affected the leukemia. Many people have a reduction or even a disappearance of leukemia cells in their blood and bone marrow. This is again called remission.

  • If the patient is in complete remission without detectable leukemia cells in the bloodstream or bone marrow, then his or her medical team watches the patient carefully over time for signs that the leukemia is coming back. In certain very high risk patients, who are likely to relapse despite a seeming remission, stem cell transplantation may follow induction therapy.
  • If the initial treatment does not cause remission, the doctor discusses alternate treatment plans, perhaps with new agents undergoing testing.

Another factor to be addressed may be impaired organ function secondary to therapy. Careful follow-up on any patient who has received extensive therapy, such as stem cell transplantation, should include careful systemic evaluations in order to initiate corrective measures should any organ impairment be detected.

Leukemia Prevention and Prognosis

No known way exists to prevent leukemia. Avoiding risk factors such as smoking, exposure to toxic chemicals, and exposure to radiation may help prevent some cases of leukemia.

The leukemias vary in their response to treatment.

  • Some types of acute leukemia respond very well to treatment and can be cured. Others do not have such a positive outlook.
  • Chronic leukemias usually cannot be cured, but they can be controlled for long periods. Some people with chronic leukemias respond well at first, but, over time, their remissions last for shorter and shorter intervals.
Specific factors are associated with outcomes in each type of leukemia. General factors associated with outcomes include the following:
  • Age
  • Percentages of leukemia cells in the blood and bone marrow
  • Degree to which specific systems of the body are affected by leukemia
  • Chromosome abnormalities in leukemia cells

Like other cancers, leukemia outlook is measured in terms of survival rates. The number of people who are still alive 5 years after treatment varies by type of leukemia. After 5 years, greater than 80% of patients without detectable disease will likely maintain a lifelong remission. Patients in remission longer than 15 years are considered unequivocal cures.

One problem that requires concerted efforts by advocate groups is the need to address the reluctance on the part of the health care industry to offer health insurance for former pediatric leukemia patients whose disease-free survivals are considered "cures" by all available evidence.

Support Groups and Counseling

Living with leukemia presents many new challenges for the patient and for their family and friends.

  • The patient will probably have many worries about how the leukemia will affect them and their ability to live a normal life, that is, to care for their family and home, to hold their job, and to continue the friendships and activities they enjoy.
  • Many people feel anxious and depressed. Some people feel angry and resentful; others feel helpless and defeated.

For most people with leukemia, talking about their feelings and concerns can be therapeutic.

  • Friends and family members can be very supportive. They may be hesitant to offer support until they see how the patient is coping. The patient should not wait for them to bring it up. If the patient wants to talk about their concerns, let them know.
  • Some people don't want to "burden" their loved ones, or they prefer talking about their concerns with a more neutral professional. A social worker, counselor, or member of the clergy can be helpful if the patient wants to discuss their feelings and concerns about having leukemia. The hematologist or oncologist should be able to recommend someone.
  • Many people with leukemia are profoundly helped by talking to other people who have leukemia. Sharing concerns with others who have been through the same thing can be remarkably reassuring. Support groups of patients and families with leukemia may be available through the medical center where the patient is receiving treatment. The American Cancer Society also has information about support groups all over the United States.

For more information about support groups, contact the following agencies:

  • American Cancer Society: 800-ACS-2345
  • National Cancer Institute, Cancer Information Service: 800-4-CANCER (800-422-6237); TTY (for deaf and hard-of-hearing callers): 800-332-8615
  • Leukemia and Lymphoma Society: 800-955-4572
Reviewed on 11/17/2017

Medically reviewed by Jay B. Zatzkin, MD; American Board of Internal Medicine with subspecialty in Medical Oncology

REFERENCE:
"Leukemia." National Cancer Institute.

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