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Leukemia in Children

Leukemia is the most common cancer in children and teens, accounting for almost 1 out of 3 cancers. Most childhood leukemias are acute lymphocytic leukemia (ALL). Most of the remaining cases are acute myeloid leukemia (AML). Chronic leukemias are rare in children.

Leukemia in Children介绍

Cancer starts when cells start to grow out of control. Cells in nearly any part of the body can become cancer. To learn more about how cancers start and spread, see What Is Cancer? For information about the differences between childhood cancers and adult cancers, see Cancer in Children.

Leukemia is a cancer that starts in early blood-forming cells found in the bone marrow, the soft inner part of certain bones. Most often, leukemia is a cancer of the white blood cells, but some leukemias start in other blood cell types.

Any of the blood-forming cells from the bone marrow can turn into a leukemia cell. Once this change takes place, the leukemia cells no longer mature in a normal way. Leukemia cells might reproduce quickly, and not die when they should. These cells build up in the bone marrow, crowding out normal cells. In most cases, the leukemia cells spill into the bloodstream fairly quickly. From there they can go to other parts of the body such as the lymph nodes, spleen, liver, central nervous system (the brain and spinal cord), testicles, or other organs, where they can keep other cells in the body from doing their jobs.

Some other childhood cancers, such as neuroblastoma or Wilms tumor, start in other organs and can spread to bone marrow, but these cancers are not leukemia.

Normal bone marrow, blood, and lymphoid tissue

To understand the different types of leukemia, it helps to know about the blood and lymph systems.

Bone marrow

Bone marrow is the soft inner part of bones. New blood cells (red blood cells, white blood cells, and platelets) are made there. In infants, active bone marrow is found in almost all bones of the body, but by the teenage years it is found mainly in the flat bones (skull, shoulder blades, ribs, and hip bones) and vertebrae (the bones that make up the spine).

Bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow. Blood stem cells go through a series of changes to make new blood cells. During this process, the cells develop into 1 of the 3 main types of blood cell components.

Types of blood cells

Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed. Having too few red blood cells in the body (anemia) can make you feel tired, weak, and short of breath because your body tissues are not getting enough oxygen.

Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in stopping bleeding by plugging up holes in blood vessels. Having too few platelets (thrombocytopenia) may cause you to bleed or bruise easily.

White blood cells help the body fight infections. Having too few white blood cells weakens your immune system and can make you more likely to get an infection.

Types of white blood cells

Lymphocytes are mature, infection-fighting cells that develop from lymphoblasts, a type of blood stem cell in the bone marrow. Lymphocytes are the main cells that make up lymphoid tissue, a major part of the immune system. Lymphoid tissue is found in the lymph nodes, thymus (a small organ behind the breast bone), spleen, tonsils and adenoids, and bone marrow. It is also scattered through the digestive system and respiratory system. There are 2 main types of lymphocytes:

  • B lymphocytes (B cells) help protect the body against germs such as bacteria and viruses. They make proteins called antibodies that attach to the germ, marking it for destruction by other parts of the immune system.
  • T lymphocytes (T cells) also help protect the body against germs. Some types of T cells destroy germs directly, while others play a role in either boosting or slowing the activity of other immune system cells.

Acute lymphocytic (lymphoblastic) leukemia (ALL), the most common type of childhood leukemia, develops from early forms of lymphocytes. It can start in either early B cells or T cells at different stages of maturity. Although both B cells and T cells can develop into leukemia, B-cell leukemias are much more common than T-cell leukemias. For more information, see the section “ How is childhood leukemia classified?”

Granulocytes are mature, infection-fighting cells that develop from myeloblasts, a type of blood-forming cell in the bone marrow. Granulocytes have granules that show up as spots under the microscope. These granules contain enzymes and other substances that can destroy germs, such as bacteria. The 3 types of granulocytes – neutrophils, basophils, and eosinophils – are distinguished under the microscope by the size and color of their granules.

Monocytes develop from blood-forming monoblasts in the bone marrow and are related to granulocytes. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them. Macrophages also help lymphocytes recognize germs and start making antibodies to fight them.

Types of leukemia in children

Leukemia is often described as being either acute (fast growing) or chronic (slow growing). Almost all childhood leukemia is acute.

Acute leukemias

The main types of acute leukemia are:

  • Acute lymphocytic (lymphoblastic) leukemia (ALL): About 3 out of 4 childhood leukemias are ALL. This leukemia starts from early forms of lymphocytes in the bone marrow.
  • Acute myelogenous leukemia (AML): This type of leukemia, also called acute myeloid leukemia, acute myelocytic leukemia, or acute non-lymphocytic leukemia, accounts for most of the remaining cases. AML starts from the myeloid cells that form white blood cells (other than lymphocytes), red blood cells, or platelets.
  • Hybrid or mixed lineage leukemia: In these rare leukemias, the cells have features of both ALL and AML. In children, they are generally treated like ALL and usually respond to treatment like ALL.

Both ALL and AML can be further divided into different subtypes. For more on these subtypes, see the section “ How is childhood leukemia classified?”

Chronic leukemias

Chronic leukemias are much more common in adults than in children. They tend to grow more slowly than acute leukemias, but they are also harder to cure. Chronic leukemias can be divided into 2 types.

  • Chronic myelogenous leukemia (CML): This leukemia rarely occurs in children. Treatment is similar to that used for adults (see “ Treatment of children with chronic myelogenous leukemia”). For more detailed information on CML, see Leukemia--Chronic Myeloid.
  • Chronic lymphocytic leukemia (CLL): This leukemia is extremely rare in children. For more information on CLL, see Leukemia--Chronic Lymphocytic.

Juvenile myelomonocytic leukemia (JMML)

This rare type of leukemia is neither chronic nor acute. It begins from myeloid cells, but it usually doesn’t grow as fast as AML or as slow as CML. It occurs most often in young children (under age 4). Symptoms can include pale skin, fever, cough, easy bruising or bleeding, trouble breathing (from too many white blood cells in the lungs), and an enlarged spleen and lymph nodes.

Leukemia in Children治疗后能活多久

When discussing cancer survival statistics, doctors often use a number called the 5-year survival rate. This refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. With acute leukemias, children who are free of the disease after 5 years are very likely to have been cured, because it’s very rare for these cancers to return after this long.

Survival rates are often based on previous outcomes of large numbers of children who had the disease, but they can’t predict what will happen in any child’s case. Knowing the type of leukemia is important in estimating a child’s outlook. But a number of other factors, including the child’s age and leukemia characteristics, can also affect outlook. Many of these factors are discussed in  Prognostic Factors In Childhood Leukemia (ALL or AML). Even when taking these other factors into account, survival rates are at best rough estimates. Your child’s doctor is likely to be a good source as to whether these numbers apply to your child, as he or she knows your situation best.

Current 5-year survival rates are based on children first diagnosed and treated more than 5 years ago. Improvements in treatment since then might result in a better outlook for children now being diagnosed.

Acute lymphocytic leukemia (ALL)

The 5-year survival rate for children with ALL has greatly increased over time and is now more than 85% overall.

Acute myelogenous leukemia (AML)

The overall 5-year survival rate for children with AML has also increased over time, and is now in the range of 60% to 70%. However, survival rates vary depending on the subtype of AML and other factors. For example, most studies suggest that the cure rate for acute promyelocytic leukemia (APL), a subtype of AML, is now higher than 80%, but rates are lower for some other subtypes of AML.

Other childhood leukemias

Accurate survival rates for less common forms of childhood leukemia are harder to find.

Juvenile myelomonocytic leukemia (JMML): For JMML, 5-year survival rates of about 50% have been reported.

Chronic leukemias: For chronic leukemias, which are rare in children, 5-year survival rates are less helpful, because some children may live for a long time with the leukemia without actually being cured. In the past, 5-year survival rates for chronic myelogenous leukemia (CML) were reported to be in the range of 60% to 80%. With newer, more effective medicines developed for CML in recent years, survival rates are likely to be higher now, although these new drugs have not been in use long enough to be sure.

Leukemia in Children治疗最新研究

Researchers are now studying the causes, diagnosis, and treatment of leukemia at many medical centers, university hospitals, and other institutions.

Genetics

As noted in Do we know what causes childhood leukemia?, scientists are making progress in understanding how changes in the DNA inside bone marrow stem cells can cause them to develop into leukemia cells. Understanding these gene changes (such as translocations or extra chromosomes) can help explain why these cells may grow out of control, and why they don’t develop into normal, mature cells. Doctors are now looking to use these changes to help them determine a child’s outlook and whether they should receive more or less intensive treatment.

This progress has already led to vastly improved and very sensitive tests for detecting leukemia cells in blood or bone marrow samples. The polymerase chain reaction (PCR) test, for example, can identify very small numbers of leukemia cells based on their chromosome translocations or other rearrangements. This test is useful in determining how completely the leukemia has been destroyed by treatment, and whether a relapse will occur if further treatment is not given.

Clinical trials

Most children with leukemia are treated at major medical centers, where treatment often means taking part in clinical trials to get the most up-to-date care. Several important questions are now being studied in clinical trials. Among them are:

  • Why do some children with acute lymphocytic leukemia (ALL) relapse after treatment, and how can this be prevented?
  • Are there other prognostic factors that will help identify which children need more or less intensive treatment?
  • Can chemotherapy drug resistance in acute myelogenous leukemia (AML) be reversed?
  • Are there better drugs or combinations of drugs for treating the different types of childhood leukemia?
  • When exactly should a stem cell transplant be used to treat leukemia?
  • How effective are stem cell transplants in children who don’t have a brother or sister who is a good tissue type match?
  • Can a second stem cell transplant help children who relapse after a first stem cell transplant?
  • What are the best treatment approaches for children with less common forms of leukemia, such as juvenile myelomonocytic leukemia (JMML) and chronic myeloid leukemia (CML)?

Immunotherapy to treat childhood leukemia

Immunotherapies are treatments that boost a child’s own immune system to help fight leukemia. Some types of immunotherapy have shown a lot of promise in treating ALL, even when other treatments are no longer working.

Chimeric antigen receptor (CAR) T-cell therapy

In this treatment, immune cells called T cells are removed from the child’s blood and genetically altered in the lab to help them attack leukemia cells. The T cells are then given back into the child’s blood, where they can seek out the leukemia cells throughout the body.

This technique has shown very encouraging results in early clinical trials against some advanced, hard-to-treat cases of ALL. In many children the leukemia could no longer be detected after treatment, although it’s not yet clear if these children have been cured.

Some children have had serious side effects from this treatment, including very high fevers, neurological changes, and dangerously low blood pressure in the days after it’s given. Doctors are learning how to manage these side effects.

Doctors are still improving how they make the T cells and are learning the best ways to use them. CAR T-cell therapy is only available at certain major medical centers at this time.

For more on this treatment, see Immunotherapy for Childhood Leukemia.

Monoclonal antibody therapy

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions, called monoclonal antibodies, can be designed to attack a specific target, such as a protein on the surface of leukemia cells.

An example is blinatumomab (Blincyto), a special kind of monoclonal antibody that can attach to 2 different proteins at the same time. One part of blinatumomab attaches to a protein found on B cells (the cells that become leukemia cells in most cases of ALL). Another part of the antibody attaches to a protein on immune cells called T cells. By binding to both of these proteins, this drug brings the leukemia cells and immune cells together, which is thought to cause the immune system to attack the cancer cells. Early results with this drug against B-cell ALL have been promising, although so far it has been studied more in adults than in children.

Leukemia in Children检查

Most of the signs and symptoms of childhood leukemia are more likely to have other causes, such as infections. Still, it’s important to let your child’s doctor know about such symptoms right away so that the cause can be found and treated, if needed.

Exams and tests will be done to determine the cause of the symptoms. If leukemia is found, further tests will be needed to find out what type it is and decide how it should be treated.

It’s important to diagnose childhood leukemia as early as possible and to determine what type of leukemia it is so that treatment can be tailored to provide the best chance of success.

Medical history and physical exam

If your child has signs and symptoms that might suggest leukemia, the doctor will want to get a thorough medical history to learn about the symptoms and how long your child has had them. The doctor may also ask about exposure to possible risk factors. A family history of cancer, especially leukemia, may also be important.

During the physical exam, the doctor will focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes, mouth, and skin will be looked at carefully, and a nervous system exam may be done. The abdomen (belly) will be felt for signs of an enlarged spleen or liver.

Tests to look for leukemia in children

If the doctor thinks your child might have leukemia, samples of your child’s blood and bone marrow will need to be checked to be sure of the diagnosis. Your child’s doctor may refer you to a pediatric oncologist, a doctor who specializes in childhood cancers (including leukemias), to have some of these tests done. If leukemia is found, other body tissue and cell samples may also be taken to help guide treatment.

Blood tests

The first tests done to look for leukemia are blood tests. The blood samples are usually taken from a vein in the arm, but in infants and younger children they may be taken from other veins (such as in the feet or scalp) or from a “finger stick.”

Blood counts and blood smears are the usual tests done on these samples. A complete blood count (CBC) is done to determine how many blood cells of each type are in the blood. For a blood smear, a small sample of blood is spread on a glass slide and looked at under a microscope. Abnormal numbers of blood cells and changes in the way these cells look may make the doctor suspect leukemia.

Most children with leukemia will have too many white blood cells and not enough red blood cells and/or platelets. Many of the white blood cells in the blood will be blasts, an early type of blood cell normally found only in the bone marrow. Even though these findings may make a doctor suspect that a child has leukemia, usually the disease can’t be diagnosed for sure without looking at a sample of bone marrow cells.

Bone marrow aspiration and biopsy

Bone marrow samples are obtained from a bone marrow aspiration and biopsy – 2 tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bones, but sometimes they may be taken from the front of the pelvic bones or from other bones.

For a bone marrow aspiration, the skin over the hip bone is cleaned and numbed by injecting a local anesthetic or applying a numbing cream. In most cases, the child is also given other medicines to make them drowsy or even go to sleep during the procedure. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out (aspirate) a small amount of liquid bone marrow.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into the bone. Once the biopsy is done, pressure will be applied to the site to help prevent any bleeding.

These bone marrow tests are used to diagnose leukemia, but they may also be repeated later to tell if the leukemia is responding to treatment.

Lumbar puncture (spinal tap)

This test is used to look for leukemia cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord.

For this test, the doctor first applies a numbing cream in an area in the lower part of the back over the spine. The doctor usually also gives the child medicine to make him or her sleep during the procedure. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.

It is very important for this test to be done by an expert. Doctors have found that if the spinal tap isn’t performed expertly and some blood leaks into the CSF, in some cases leukemia cells may get into the fluid and grow there.

In children already diagnosed with leukemia, the first lumbar puncture is also used to give chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.

Lymph node biopsy

This type of biopsy is important in diagnosing lymphomas, but it is rarely needed for children with leukemias.

During this procedure, a surgeon cuts through the skin to remove an entire lymph node (excisional biopsy). If the node is near the skin surface, this is a simple operation. But it is more involved if the node is inside the chest or abdomen. Most often the child will need general anesthesia (where the child is asleep).

Lab tests to diagnose and classify leukemia

Microscopic exams

As mentioned above, blood counts and smears are usually the first tests done when leukemia is a possible diagnosis. Any other samples taken (bone marrow, lymph node tissue, or CSF) are also looked at under a microscope. The samples might be exposed to chemical stains (dyes) that can cause color changes in some types of leukemia cells.

Doctors will look at the size, shape, and staining patterns of the blood cells in the samples to classify them into specific types. 

A key element is whether the cells look mature (like normal blood cells) or immature (lacking features of normal blood cells). The most immature cells are called blasts. Having too many blasts in the sample, especially in the blood, is a typical sign of leukemia.

An important feature of a bone marrow sample is its cellularity. Normal bone marrow contains a certain number of blood-forming cells and fat cells. Marrow with too many blood-forming cells is said to be hypercellular. If too few blood-forming cells are found, the marrow is called hypocellular.

Flow cytometry and immunohistochemistry

These tests are used for immunophenotyping – classifying leukemia cells based on certain proteins in or on the cells. This kind of testing is very helpful in determining the exact type of leukemia. It is most often done on cells from bone marrow, but it can also be done on cells from the blood, lymph nodes, and other body fluids.

For both flow cytometry and immunohistochemistry, samples of cells are treated with antibodies that stick to certain proteins. For immunohistochemistry, the cells are then examined under a microscope to see if the antibodies stuck to them (meaning they have these proteins), while for flow cytometry a special machine is used.

Flow cytometry can also be used to estimate the amount of DNA in the leukemia cells. This is important to know, especially in ALL, because cells with more DNA than normal (a DNA index of 1.16 or higher) are often more sensitive to chemotherapy, and these leukemias have a better prognosis (outlook).

Flow cytometry can also be used to measure the response to treatment and the existence of minimal residual disease (MRD) in some types of leukemias. See Prognostic Factors in Childhood Leukemia.

Chromosome tests

Normal human cells have 23 pairs of chromosomes (strands of DNA), each of which is a certain size and looks a certain way under the microscope. But in some types of leukemia, the cells have changes in their chromosomes.

For instance, sometimes 2 chromosomes swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. This change, called a translocation, can usually be seen under a microscope. Other types of chromosome changes are also possible. Recognizing these changes can help identify certain types of acute leukemias and can help determine prognosis (outlook).

Some types of leukemia have cells with an abnormal number of chromosomes (instead of the usual 46) – they may be missing some chromosomes or have extra copies of some. This can also affect a patient’s outlook. For example, in ALL, chemotherapy is more likely to work if the cells have more than 50 chromosomes and is less likely to work if the cells have fewer than 46 chromosomes.

Finding these types of chromosome changes with lab tests can be very helpful in predicting a person’s outlook and response to treatment.

Cytogenetics: For this test, leukemia cells are grown in a lab dish and the chromosomes are looked at under a microscope to detect any changes, including missing or extra chromosomes. (Counting the number of chromosomes by cytogenetics provides similar information to measuring the DNA index by flow cytometry, as described above.)

Cytogenetic testing usually takes about 2 to 3 weeks because the leukemia cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be looked at under the microscope.

Not all chromosome changes can be seen under a microscope. Other lab tests can often help detect these changes.

Fluorescent in situ hybridization (FISH): This is another way to look at chromosomes and genes. It uses pieces of DNA that only attach to specific parts of particular chromosomes. The DNA is linked to fluorescent dyes that can be seen with a special microscope. FISH can find most chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

FISH can be used to look for specific changes in chromosomes. It can be used on blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days.

Polymerase chain reaction (PCR): This is a very sensitive test that can also find some chromosome changes too small to be seen under a microscope, even if there are very few leukemia cells in a sample. This test can be very useful in looking for small numbers of leukemia cells (minimal residual disease, or MRD) during and after treatment that might not be detected with other tests.

Other blood tests

Children with leukemia will have tests to measure certain chemicals in the blood to check how well their body systems are working.

These tests aren’t used to diagnose leukemia, but in children already known to have it, they can help find damage to the liver, kidneys, or other organs caused by the spread of leukemia cells or by certain chemotherapy drugs. Tests are also often done to measure blood levels of important minerals, as well as to make sure the blood is clotting properly.

Children might also be tested for blood infections. It’s important to diagnose and treat infections in children with leukemia quickly because their weakened immune systems can allow infections to spread.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to make pictures of the inside of the body. Leukemia doesn’t usually form tumors, so imaging tests aren’t as useful as they are for other types of cancer. But if leukemia is suspected or has been diagnosed, your child’s doctor may order some of these tests to get a better idea of the extent of the disease or to look for other problems, such as infections. For more details, see Imaging Tests.

Chest x-rays

A chest x-ray can help detect an enlarged thymus or lymph nodes in the chest. If the test result is abnormal, a computed tomography (CT) scan of the chest may be done to get a more detailed view.

Chest x-rays can also help look for pneumonia if your child might have a lung infection.

Computed tomography (CT) scan

The CT scan isn’t usually needed to diagnose leukemia, but it might be done if the doctor suspects the leukemia is growing in lymph nodes in the chest or in organs like the spleen or liver. It is also sometimes used to look at the brain and spinal cord, but an MRI scan may also be used for this.

PET/CT scan: Some machines combine the CT scan with a positron emission tomography (PET) scan. For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body within a day or so.) Because cancer cells grow rapidly, they absorb large amounts of the sugar. A special camera can then create a picture of areas of radioactivity in the body. The picture from the PET scan is not detailed like those from a CT scan, but it provides helpful information about the whole body. The PET/CT scan lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan.

Magnetic resonance imaging (MRI) scan

An MRI scan, like a CT scan, makes detailed images of soft tissues in the body. It’s most helpful in looking at the brain and spinal cord, so it’s most likely to be done if the doctor has reason to think the leukemia might have spread there (such as if the child has symptoms like headaches, seizures, or vomiting).

Ultrasound

Ultrasound can be used to look at lymph nodes near the surface of the body or to look for enlarged organs inside the abdomen such as the kidneys, liver, and spleen. (It can’t be used to look at organs or lymph nodes in the chest because the ribs block the sound waves.)

This is a fairly easy test to have, and it uses no radiation. Your child simply lies on a table, and a technician moves the transducer over the part of the body being looked at.

Bone scan

Bone scans are not done often for childhood leukemias, but it may be useful if your child has bone pain that might be from either an infection or cancer in the bones. If your child has already been diagnosed with leukemia or if a PET scan (described above) has already been done, there is usually no need for a bone scan.

 

Leukemia in Children症状

Many of the symptoms of childhood leukemia can have other causes as well, and most often these symptoms are not caused by leukemia. Still, if your child has any of them, it’s important to have your child seen by a doctor so the cause can be found and treated, if needed.

The symptoms of leukemia are often caused by problems in the child’s bone marrow, which is where the leukemia begins. As leukemia cells build up in the marrow, they can crowd out the normal blood cell-making cells. As a result, a child may not have enough normal red blood cells, white blood cells, and blood platelets. These shortages show up on blood tests, but they can also cause symptoms. The leukemia cells might also invade other areas of the body, which can also cause symptoms.

Symptoms from low red blood cell counts (anemia): Red blood cells carry oxygen to all of the cells in the body. A shortage of red blood cells can cause:

  • Tiredness (fatigue)
  • Weakness
  • Feeling cold
  • Feeling dizzy or lightheaded
  • Headaches
  • Shortness of breath
  • Pale skin

Symptoms from low white blood cell counts:

  • Infections can occur because of a shortage of normal white blood cells. Children with leukemia can get infections that don’t seem to go away or may get one infection after another. Although children with leukemia often have high white blood cell counts because they have so many leukemia cells, these cells don’t protect against infection the way normal white blood cells do.
  • Fever is often the main sign of infection. But some children might have a fever without having an infection.

Symptoms from low blood platelet counts: Platelets in the blood normally help stop bleeding. A shortage of platelets can lead to:

  • Easy bruising and bleeding
  • Frequent or severe nosebleeds
  • Bleeding gums

Bone or joint pain: This pain is caused by the buildup of leukemia cells near the surface of the bone or inside the joint.

Swelling of the abdomen (belly): Leukemia cells can collect in the liver and spleen, making them bigger. This might be noticed as a fullness or swelling of the belly. The lower ribs usually cover these organs, but when they are enlarged the doctor can often feel them.

Loss of appetite and weight loss: If the spleen and/or liver get big enough, they can press against other organs like the stomach. This can make the child feel full after eating only a small amount of food, leading to a loss of appetite and weight loss over time.

Swollen lymph nodes: Some leukemias spread to lymph nodes. Swollen nodes may be seen or felt as lumps under the skin in certain areas of the body (such as on the sides of the neck, in underarm areas, above the collarbone, or in the groin). Lymph nodes inside the chest or abdomen can also swell, but these can only be seen on imaging tests, such as CT or MRI scans.

In infants and children, lymph nodes often get bigger when they are fighting an infection. An enlarged lymph node in a child is much more often a sign of infection than leukemia, but it should be checked by a doctor and followed closely.

Coughing or trouble breathing: Some types of leukemia can affect structures in the middle of the chest, such as lymph nodes or the thymus (a small organ in front of the trachea, the breathing tube that leads to the lungs). An enlarged thymus or lymph nodes in the chest can press on the trachea, causing coughing or trouble breathing. In some cases where the white blood cell count is very high, the leukemia cells can build up in the small blood vessels of the lungs, which can also cause trouble breathing.

Swelling of the face and arms: The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. An enlarged thymus may press on the SVC, causing the blood to “back up” in the veins. This is known as SVC syndrome. It can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. The SVC syndrome can be life-threatening, and needs to be treated right away.

Headache, seizures, vomiting: A small number of children have leukemia that has already spread to the brain and spinal cord when they are first diagnosed. This can lead to symptoms such as headache, trouble concentrating, weakness, seizures, vomiting, problems with balance, and blurred vision.

Rashes, gum problems: In children with acute myelogenous leukemia (AML), leukemia cells may spread to the gums, causing swelling, pain, and bleeding. If it spreads to the skin, it can cause small, dark spots that look like common rashes. A collection of AML cells under the skin or in other parts of the body is called a chloroma or granulocytic sarcoma.

Extreme fatigue, weakness: A rare but very serious consequence of AML is extreme tiredness, weakness, and slurring of speech. This can occur when very high numbers of leukemia cells cause the blood to become too thick and slow the circulation through small blood vessels of the brain.

Again, most of the symptoms above are more likely to be caused by something other than leukemia. Still, it’s important to have these symptoms checked by a doctor so the cause can be found and treated, if needed.

美国Leukemia in Children治疗统计数据

Leukemia is the most common cancer in children and teens, accounting for almost 1 out of 3 cancers. Overall, however, childhood leukemia is a rare disease.

About 3 out of 4 leukemias among children and teens are acute lymphocytic leukemia (ALL). Most of the remaining cases are acute myelogenous leukemia (AML).

ALL is most common in early childhood, peaking between 2 and 4 years of age. Cases of AML are more spread out across the childhood years, but this type of leukemia is slightly more common during the first 2 years of life and during the teenage years.

ALL is slightly more common among Hispanic and white children than among African-American and Asian-American children, and it is more common in boys than in girls. AML occurs about equally among boys and girls of all races.

Chronic leukemias are rare in children. Most of these are chronic myelogenous leukemia (CML), which tends to occur more in teens than in younger children.

Juvenile myelomonocytic leukemia (JMML) usually occurs in young children, with an average age of about 2.

Visit the American Cancer Society’s Cancer Statistics Center for more key statistics.

Survival statistics for childhood leukemia are in another section of this document.

Leukemia in Children致病因素

A risk factor is anything that affects a person’s chance of getting a disease such as cancer. Different cancers have different risk factors.

Lifestyle-related risk factors such as tobacco use, diet, body weight, and physical activity play a major role in many adult cancers. But these factors usually take many years to influence cancer risk, and they are not thought to play much of a role in childhood cancers, including leukemias.

There are a few known risk factors for childhood leukemia.

Genetic risk factors

Genetic risk factors are those that are part of our DNA (the substance that makes up our genes). They are most often inherited from our parents. While some genetic factors increase the risk of childhood leukemia, most leukemias are not linked to any known genetic causes.

Inherited syndromes

Some inherited disorders increase a child’s risk of developing leukemia:

  • Down syndrome (trisomy 21): Children with Down syndrome have an extra (third) copy of chromosome 21. They are many times more likely to develop either acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) than are other children, with an overall risk of about 2% to 3%. Down syndrome has also been linked with transient leukemia (also known as transient myeloproliferative disorder) – a leukemia-like condition within the first month of life, which often resolves on its own without treatment.
  • Li-Fraumeni syndrome: This is a rare condition caused by a change in the TP53 tumor suppressor gene. People with this change have a higher risk of developing several kinds of cancer, including leukemia, bone or soft tissue sarcomas, breast cancer, adrenal gland cancer, and brain tumors.

Other genetic disorders (such as neurofibromatosis and Fanconi anemia) also carry an increased risk of leukemia, as well as some other types of cancers.

Inherited immune system problems

Certain inherited conditions cause children to be born with immune system problems. These include:

  • Ataxia-telangiectasia
  • Wiskott-Aldrich syndrome
  • Bloom syndrome
  • Schwachman-Diamond syndrome

Along with an increased risk of getting serious infections from reduced immune defenses, these children might also have an increased risk of leukemia.

Having a brother or sister with leukemia

Siblings (brothers and sisters) of children with leukemia have a slightly increased chance (2 to 4 times normal) of developing leukemia, but the overall risk is still low. The risk is much higher among identical twins. If one twin develops childhood leukemia, the other twin has about a 1 in 5 chance of getting leukemia as well. This risk is much higher if the leukemia develops in the first year of life.

Having a parent who develops leukemia as an adult does not seem to raise a child’s risk of leukemia.

Lifestyle-related risk factors

Lifestyle-related risk factors for some adult cancers include smoking, being overweight, drinking too much alcohol, and getting too much sun exposure. These types of factors are important in many adult cancers, but they are unlikely to play a role in most childhood cancers.

Some studies have suggested that a woman drinking a lot of alcohol during pregnancy might increase the risk of leukemia in her child, but not all studies have found such a link.

Environmental risk factors

Environmental risk factors are influences in our surroundings, such as radiation and certain chemicals, that increase the risk of getting diseases such as leukemias.

Radiation exposure

Exposure to high levels of radiation is a risk factor for childhood leukemia. Japanese atomic bomb survivors had a greatly increased risk of developing AML, usually within 6 to 8 years after exposure. If a fetus is exposed to radiation within the first months of development, there may also be an increased risk of childhood leukemia, but the extent of the risk is not clear.

The possible risks from fetal or childhood exposure to lower levels of radiation, such as from x-ray tests or CT scans, are not known for sure. Some studies have found a slight increase in risk, while others have found no increased risk. Any risk increase is likely to be small, but to be safe, most doctors recommend that pregnant women and children not get these tests unless they are absolutely needed.

Exposure to chemotherapy and certain other chemicals

Children and adults treated for other cancers with certain chemotherapy drugs have a higher risk of getting a second cancer, usually AML, later in life. Drugs such as cyclophosphamide, chlorambucil, etoposide, and teniposide have been linked to a higher risk of leukemia. These leukemias usually develop within 5 to 10 years of treatment, and they tend to be hard to treat.

Exposure to chemicals such as benzene (a solvent used in the cleaning industry and to manufacture some drugs, plastics, and dyes) may cause acute leukemia in adults and, rarely, in children. Chemical exposure is more strongly linked to an increased risk of AML than to ALL.

Several studies have found a possible link between childhood leukemia and household exposure to pesticides, either during pregnancy or early childhood. Some studies have also found a possible increased risk among mothers with workplace exposure to pesticides before birth. However, most of these studies had serious limitations in the way they were done. More research is needed to try to confirm these findings and to provide more specific information about the possible risks.

Immune system suppression

Children who are getting intensive treatment to suppress their immune system (mainly children who have had organ transplants) have an increased risk of certain cancers, such as lymphoma and ALL.

Uncertain, unproven, or controversial risk factors

Other factors that have been studied for a possible link to childhood leukemia include:

  • Exposure to electromagnetic fields (such as living near power lines)
  • Living near a nuclear power plant
  • Infections early in life
  • Mother’s age when child is born
  • Parent’s smoking history
  • Fetal exposure to hormones such as diethylstilbestrol (DES) or birth control pills
  • Father’s workplace exposure to chemicals and solvents
  • Chemical contamination of ground water

So far, most studies have not found strong links between any of these factors and childhood leukemia. Researchers continue to study these exposures.

导致Leukemia in Children的因素

The exact cause of most childhood leukemias is not known. Most children with leukemia do not have any known risk factors.

Still, scientists have learned how certain changes in the DNA inside normal bone marrow cells can cause them to become leukemia cells. Normal human cells grow and function based mainly on the information in each cell’s DNA. The DNA inside our cells makes up our genes, which are the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But our genes affect more than how we look.

Some genes control when our cells grow, divide into new cells, and die at the right time. Certain genes that help cells grow, divide, or stay alive are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA mutations (or other types of changes) that turn on oncogenes or turn off tumor suppressor genes. These gene changes can be inherited from a parent (as is sometimes the case with childhood leukemias), or they may happen randomly during a person’s lifetime if cells in the body make mistakes as they divide to make new cells.

A common type of DNA change that can lead to leukemia is known as a chromosome translocation. Human DNA is packaged in 23 pairs of chromosomes. In a translocation, DNA from one chromosome breaks off and becomes attached to a different chromosome. The point on the chromosome where the break occurs can affect oncogenes or tumor suppressor genes. For example, a translocation seen in nearly all cases of childhood chronic myeloid leukemia (CML) and in some cases of childhood acute lymphocytic leukemia (ALL) is a swapping of DNA between chromosomes 9 and 22, which leads to what is known as the Philadelphia chromosome. This creates an oncogene known as BCR-ABL. Many other changes in chromosomes or in specific genes have been found in childhood leukemias as well.

Some children inherit DNA mutations from a parent that increase their risk for cancer (see the section “ What are the risk factors for childhood leukemia?”). For instance, a condition called Li-Fraumeni syndrome, which results from an inherited mutation of the TP53 tumor suppressor gene, increases a person’s risk of developing leukemia, as well as some other cancers.

Certain inherited diseases can increase the risk of developing leukemia, but most childhood leukemias do not seem to be caused by inherited mutations. Usually, DNA mutations related to leukemia develop after conception rather than having been inherited. Some of these acquired mutations might occur early, even before birth. In rare cases, acquired mutations can result from exposure to radiation or cancer-causing chemicals, but most often they occur for no apparent reason.

A few studies have suggested that some childhood leukemias may be caused by a combination of genetic and environmental factors. For example, certain genes normally control how our bodies break down and get rid of harmful chemicals. Some people have different versions of these genes that make them less effective. Children who inherit these genes may not be as able to break down harmful chemicals if they are exposed to them. The combination of genetics and exposure might increase their risk for leukemia.

Leukemia in Children早期发现

At this time there are no widely recommended blood tests or other screening tests for most children to look for leukemia before it starts to cause symptoms. Childhood leukemia is often found because a child has symptoms that prompt a visit to the doctor. The doctor then orders blood tests, which come back as abnormal and point to the diagnosis. The best way to find these leukemias early is to pay attention to the possible signs and symptoms of this disease (see Signs and Symptoms of Childhood Leukemia).

For children known to be at increased risk of leukemia (because of Li-Fraumeni syndrome or Down syndrome, for example), most doctors recommend careful, regular medical checkups and possibly other tests. The same is true for children who have been treated with chemotherapy and/or radiation therapy for other cancers, and for children who have had organ transplants and are taking immune system-suppressing drugs. The risk of leukemia in these children, although higher than in the general population, is still small.

Late and Long-term Effects of Treatment of Childhood Leukemia

Because of major advances in treatment, most children treated for leukemia now live into adulthood, so their health as they get older has gotten more focus in recent years.

Just as the treatment of childhood leukemia requires a very specialized approach, so does the care and follow-up after treatment. The earlier problems are recognized, the more likely it is they can be treated effectively.

Childhood leukemia survivors are at risk, to some degree, for several possible late effects of their treatment. This risk depends on a number of factors, such as the type of leukemia, the type and doses of treatments they received, and the age of the child at the time of treatment. It’s important to discuss what these possible effects might be with your child’s medical team so you know what to watch for and report to the doctor.

Second cancers: Children who have been treated for leukemia are at higher risk of developing other cancers later in life. One of the most serious possible side effects of acute lymphocytic leukemia (ALL) therapy is a small risk of getting acute myelogenous leukemia (AML) later on. This occurs in about 5% of patients after getting chemotherapy drugs called epipodophyllotoxins (etoposide, teniposide) or alkylating agents (cyclophosphamide, chlorambucil). Of course, the risk of getting these second cancers must be balanced against the obvious benefit of treating a life-threatening disease such as leukemia.

Heart and lung problems: Certain chemotherapy drugs or radiation therapy to the chest can sometimes cause heart or lung problems later in life. The risks of heart disease and stroke are much higher among those treated for ALL as children, so careful follow-up is very important. ALL survivors are also more likely to be overweight and to have high blood pressure, which can contribute to these problems.

Learning problems: Treatment that includes radiation therapy to the brain or some types of chemotherapy may affect learning ability in some children. Because of this, doctors try to limit treatments that could affect the brain (including radiation) as much as possible.

Growth and development: Some cancer treatments may affect a child’s growth, so they may end up a bit shorter as adults. This is especially true after stem cell transplants. This can be helped by treating survivors with growth hormone, if needed.

Fertility issues: Cancer treatment may also affect sexual development and ability to have children later in life. Talk to your child’s cancer care team about the risks of infertility with treatment, and ask if there are options for preserving fertility, such as sperm banking. For more information, see Fertility and Women With Cancer and Fertility and Men With Cancer.

Bone problems: Bone damage or osteoporosis (thinning of the bones) may result from the use of prednisone, dexamethasone, or other steroid drugs.

There may be other possible complications from chemotherapy as well. Your child’s doctor should carefully review any possible problems with you before your child starts treatment.

Along with physical side effects, some childhood leukemia survivors might have emotional or psychological issues. They might also have problems with normal functioning and school work. These can often be addressed with support and encouragement. If needed, doctors and other members of the health care team can recommend special support programs and services to help children after cancer treatment.

Long-term follow-up guidelines

To help increase awareness of late effects and improve follow-up care for childhood cancer survivors throughout their lives, the Children’s Oncology Group (COG) has developed long-term follow-up guidelines for survivors of childhood cancers. These guidelines can help you know what to watch for, what types of screening tests should be done, and how late effects can be treated.

It’s very important to discuss possible long-term complications with your child’s health care team, and to make sure there is a plan in place to watch for these problems and treat them, if needed. To learn more, ask your child’s doctors about the COG survivor guidelines. You can also read them on the COG website: www.survivorshipguidelines.org. The guidelines are written for health care professionals. Patient versions of some of the guidelines are available (as “Health Links”) on the site as well, but we urge you to discuss them with your doctor.

For more about some of the possible long-term effects of treatment, see Children Diagnosed With Cancer: Late Effects of Cancer Treatment.

Leukemia in Children术后生活注意事项

During and after treatment for childhood leukemia, the main concerns for most families are the short- and long-term effects of the leukemia and its treatment, and concerns about the leukemia coming back.

It’s certainly normal to want to put the leukemia and its treatment behind you and to get back to a life that doesn’t revolve around cancer. But it’s important to realize that follow-up care is a central part of this process that offers your child the best chance for recovery and long-term survival.

Follow-up exams

For several years after treatment, regular follow-up exams will be very important. The doctors will watch for possible signs of leukemia, as well as for short-term and long-term side effects of treatment.

Checkups typically include careful physical exams, lab tests, and sometimes, imaging tests. These checkups will usually be monthly during the first year, and then less often for at least 5 years after therapy. After that time, most children see their doctor at least yearly for a checkup.

If leukemia does come back, it is most often while the child is still being treated or within a year or so after finishing treatment. It is unusual for an acute leukemia (ALL or AML) to return if there are no signs of the disease within the next 2 years.

A benefit of follow-up care is that it gives you a chance to discuss questions and concerns that come up during and after your child’s recovery. For example, almost any cancer treatment can have side effects. Some go away soon after treatment, but others can last a long time, or might not even show up until years later. It’s important to report any new symptoms to the doctor right away, so that the cause can be found and treated, if needed.

Keeping good medical records

As much as you might want to put the experience behind you once treatment is done, it’s very important to keep good records of your child’s medical care during this time. This can be very helpful later on as your child changes doctors. Gathering the details during or soon after treatment may be easier than trying to get them at some point in the future. Be sure the doctors have the following information (and always keep copies for yourself):

  • A copy of the pathology reports from any biopsies or surgeries.
  • If your child had surgery, a copy of the operative report.
  • If your child stayed in the hospital, copies of the discharge summaries that the doctor wrote when your child was sent home.
  • A list of the final doses of each chemotherapy drug or other drug your child received. (Certain drugs have specific long-term side effects.)
  • If radiation therapy was given, a summary of the type and dose of radiation and when and where it was given.
  • The names and contact information of the doctors who treated your child’s leukemia.

It’s also very important to keep health insurance coverage. Tests and doctor visits cost a lot, and even though no one wants to think of the leukemia coming back, this could happen.