What is acute myelogenous leukemia?
Acute myelogenous leukemia (AML), also called acute myeloid leukemia or acute myelocytic leukemia, is the second most common blood cancer in children. AML affects about 500 children in the U.S. each year. There are several subtypes of AML.
Each AML subtype starts in the young cells that form normal mature blood cells. One subtype, acute promyelocytic leukemia, is treated differently than the other types of AML.
Signs and symptoms of AML
The most common signs and symptoms of acute myelogenous leukemia in children are:
- Anemia. Anemia occurs when normal red blood cells can’t be produced because the bone marrow is overcrowded by leukemia cells. The anemic child may be more tired, take more naps, look pale, and her heart may be racing. The number of red blood cells on a blood count (expressed as “hemoglobin” or “hematocrit”) will be below normal.
- Bleeding and/or bruising. When the bone marrow cannot produce enough platelets, bleeding can occur, especially when the platelet numbers are less than 10-20,000/mm3. Low platelets can cause a child to bruise or bleed more easily.
- Bone and joint pain. Pain in bones and joints is usually a result of the bone marrow being crowded with leukemic blasts. This is often mistaken for “growing pains.”
- Recurrent fevers/infections. The child with leukemia often shows non-specific symptoms of infection such as fever and fatigue. Although the blood count of a child with leukemia may show a high number of white blood cells, these cells are immature and do not normally fight infection. As a result, the child may have difficulty recovering from an ordinary childhood infection or may develop unusual infections.
- Abdominal pain. Leukemia cells can collect in the kidneys, liver and spleen, causing enlargement of these organs which can cause pain in the abdomen. This pain may lead to loss of appetite and weight loss.
- Swollen lymph nodes. Lymph nodes filter the blood. Leukemia cells often collect in the nodes, causing swelling. Swelling occurs in lymph nodes in the neck, under the arms, in the groin and chest. Sometimes it is difficult to distinguish the lymph nodes of leukemia from those that are a normal part of the body’s response to infection or allergy.
- Difficulty breathing. In leukemia, cells can clump together in the thymus a gland under the breastbone and around the throat. This mass of cells can cause difficulty breathing. Any wheezing, coughing and/or labored or painful breathing requires immediate medical attention.
Diagnosis of AML
The diagnosis of acute myelogenous leukemia in children is based on a complete medical history and physical examination and on the following diagnostic tests:
- Complete blood count (CBC). The CBC checks the numbers of white blood cells, red blood cell, and platelets in the blood. In leukemia, the white cell count may be lower or higher than normal and the red blood cell count and platelet count is often lower than normal.
- Bone marrow aspirate and biopsy. Bone marrow aspirates and biopsies involve inserting a needle into a bone in the pelvis and removing about 2 teaspoons of marrow for examination. Bone marrow studies require pain medicine and often sedation or general anesthesia.
- Lumbar puncture (spinal tap). Spinal taps involve inserting a needle into the lower back, between the bones of the backbone to remove the fluid that surrounds the brain and spinal cord. The same needle can be used to give chemotherapy to prevent or treat leukemia in the brain or spinal cord.
- Chest X-ray. Chest X-rays are taken to see if there is a mass of leukemia cells in the chest that may affect breathing.
Treatment for AML
Treatment for acute myelogenous leukemia usually begins by addressing the signs and symptoms your child has such as anemia, bleeding and/or infection. In addition, treatment for leukemia may include some or all of the following:
- Chemotherapy. Chemotherapy refers to medicines that help fight cancer. They are given by mouth, in the vein, in the muscle or under the skin. Intrathecal chemotherapy is chemotherapy that is injected into the spinal fluid to prevent or treat leukemia in the brain and spinal cord.
- Blood and marrow transplantation. Blood and marrow transplantation consists of three steps: 1) collection of healthy stem cells from a donor without cancer or from the patient himself or herself; 2) administration of high doses of chemotherapy and possibly radiation therapy to kill any remaining leukemia cells; and 3) infusion of the healthy stem cells through an intravenous line to produce normal blood-forming cells. Bone marrow or stem cell transplantation is commonly used to treat AML that has not responded to chemotherapy.
- Blood transfusions. Blood transfusions are sometimes used for patients who have anemia who cannot make their own red blood cells. Platelets are commonly transfused when platelet counts are low. White blood cells are occasionally transfused to treat severe infections that do not respond to antibiotics. Plasma, the fluid part of blood in which the blood cells are suspended, is transfused in patients who are not able to make the proteins that clot the blood.
- Antibiotics. Antibiotics are used to prevent or treat infections.
Treatment stages
Treatment of pediatric AML takes six to nine months and involves four courses of chemotherapy and may also involve stem cell transplantation.
Can Childhood Leukemia Be Found Early?
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 signs or symptoms that prompt a visit to the doctor. The doctor then orders blood tests, which might point to leukemia as the cause. The best way to find these leukemias early is to pay attention to the possible signs and symptoms of this disease.
For children at increased risk
For children known to be at increased risk of leukemia (because of a genetic condition such as 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.
Prevention
There are very few known lifestyle-related or environmental causes of childhood leukemias, so it is important to know that in most cases there is nothing these children or their parents could have done to prevent these cancers.
Survival Rates for Childhood Leukemias
Survival rates are often used by doctors as a standard way of discussing a child’s prognosis (outlook). These numbers tell you what portion of children in a similar situation (such as with the same type and subtype of leukemia) are still alive a certain amount of time after they were diagnosed. They can’t tell you exactly what will happen in an individual child’s case, but they may help give you a better understanding about how likely it is that treatment will be successful. Some people find survival rates helpful, but some people might not.
The 5-year survival rate refers to the percentage of children who live at least 5 years after their leukemia is diagnosed. With acute leukemias (ALL or AML), 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.
Knowing the type and subtype 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 can probably tell you how these numbers apply to your child.
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 about 90% overall. In general, children in lower risk groups have a better outlook than those in higher risk groups. But it’s important to know that even children in higher risk groups can often still be cured.
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 65% 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 myeloid leukemia (CML)
For CML, which is 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 CML were reported to be in the range of 60% to 80%. But with the newer, more effective medicines used to treat CML in recent years, survival rates are likely to be higher now.
Prognostic Factors in Childhood Leukemia ( ALL or AML )
In children with acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML), certain factors that can affect a child’s outlook (prognosis) are called prognostic factors. They help doctors decide how intense treatment needs to be. Prognostic factors seem to be more important in ALL than in AML.
Prognostic factors for children with ALL
Children with ALL are often put into risk groups (such as low risk, standard risk, high risk, or very high risk), with more intensive treatment given to higher risk patients. Generally, children at low risk have a better outlook than those at very high risk. But it’s important to know that even children in higher risk groups can often still be cured.
While all of the following are prognostic factors, only certain ones are used to determine which risk group a child is in. (The first 2 factors – age at diagnosis and initial white blood cell count – are thought to be the most important.)
Age at diagnosis
Children between the ages of 1 and 9 with B-cell ALL tend to have better cure rates. Children younger than 1 year and children 10 years or older are considered high-risk patients. The outlook in T-cell ALL isn’t affected much by age.
Initial white blood cell (WBC) count
Children with ALL who have very high WBC counts (greater than 50,000 cells per cubic millimeter) when they are diagnosed are at higher risk and need more intensive treatment.
ALL subtype
Children with early B-cell ALL subtypes generally do better than those with mature B-cell (Burkitt) leukemia. The outlook for T-cell ALL seems to be about the same as that for B-cell ALL as long as treatment is intense enough.
Gender
Girls with ALL may have a slightly higher chance of being cured than boys, but as treatments have improved in recent years, this difference has shrunk.
Number of chromosomes in the leukemia cells (ploidy)
Normal human cells have 46 chromosomes. Children are more likely to be cured if their leukemia cells have more than 50 chromosomes (called hyperdiploidy), especially if there is an extra chromosome 4, 10, or 17. Hyperdiploidy can also be expressed as a DNA index of more than 1.16. Children whose leukemia cells have fewer than 44 chromosomes (known as hypodiploidy) have a less favorable outlook.
Chromosome changes (such as translocations)
Translocations occur when chromosomes swap some of their genetic material (DNA). Children whose leukemia cells have a translocation between chromosomes 12 and 21 are more likely to be cured. Those with a translocation between chromosomes 9 and 22 (the Philadelphia chromosome) or 4 and 11 tend to have a less favorable prognosis. Some of these “poor” prognostic factors have become less important in recent years as treatment has improved.
Response to initial treatment
Children whose leukemia goes into remission (major reduction of cancer cells in the bone marrow) within 1 to 2 weeks of chemotherapy have a better outlook than those whose leukemia does not. Having minimal residual disease (MRD), which is a very small amount of leukemia cells still detectable by sensitive lab tests, can also affect outlook. (See “Status of acute leukemia after treatment” below for more on this.) Children whose cancer does not respond as well may be given more intensive chemotherapy.
Prognostic factors for children with AML
Prognostic factors are not quite as important in predicting outcome or in guiding treatment for AML as they are for ALL.
Initial white blood cell (WBC) count
Children with AML whose WBC count is less than 100,000 cells per cubic millimeter at diagnosis tend to do better than those with higher counts.
Down syndrome
Children with Down syndrome who develop AML tend to have a good outlook, especially if the child is 4 years old or younger at the time of diagnosis.
AML subtype
Some subtypes of AML tend to have a better outlook than others. For example, the acute promyelocytic leukemia (APL) subtype tends to have a better outlook than most other subtypes.
Chromosome or gene changes
Children with leukemia cells that have translocations between chromosomes 15 and 17 (seen in most cases of APL) or between 8 and 21, or with an inversion (rearrangement) of chromosome 16 have a better chance of being cured. Children whose leukemia cells are missing a copy of chromosome 5 or 7 (known as monosomy) or just part of chromosome 5 (known as a deletion) tend to have a poorer prognosis.
Children whose leukemia cells have a mutation in the FLT3 gene tend to have a poorer outlook, although new drugs that target cells with this abnormal gene might lead to better outcomes. On the other hand, children whose leukemia cells have changes in the NPM1 gene (and not in the FLT3 gene) seem to have a better prognosis than children without this change. Changes in the CEBPA gene are also linked to a better outcome.
Myelodysplastic syndrome or secondary AML
Children who first have a myelodysplastic syndrome (“smoldering leukemia”) or whose leukemia is the result of treatment for another cancer tend to have a less favorable outlook.
Response to initial treatment
Children whose leukemia responds quickly to treatment (only one chemotherapy cycle needed to achieve remission) are more likely to be cured than those whose leukemia takes longer to respond or does not respond at all.
Status of acute leukemia after treatment
How well (and how quickly) ALL or AML responds to the initial (induction) treatment can affect long-term prognosis.
Remission
A remission (or complete remission) is usually defined as having no evidence of leukemia after the initial treatment. This means:
- The bone marrow contains fewer than 5% blast cells
- The blood cell counts are within normal limits
- There are no signs or symptoms of the disease
A complete molecular remission means there is no evidence of leukemia cells in the bone marrow, even when using very sensitive lab tests, such as polymerase chain reaction (PCR).
Even when leukemia is in remission, this does not always mean that it has been cured.
Minimal residual disease
Minimal residual disease (MRD) is a term used after treatment when leukemia cells can’t be found in the bone marrow using standard lab tests (such as looking at cells under a microscope), but they can still be detected with more sensitive tests (such as flow cytometry or PCR).
In general, children with MRD during or after induction chemotherapy are more likely to have the leukemia relapse (come back) and therefore may need more intense treatment. Children with more MRD have a greater risk of relapse than those with less MRD.
Active disease
Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has relapsed (come back) after treatment. For a patient to have relapsed, more than 5% of the bone marrow must be made up of blast cells.
Post-chemotherapy or transplant Revaccination Clinic
It is common for patients who have undergone blood or marrow transplant (BMT) to lose the immunity they had acquired through vaccinations. This loss is due to a variety of reasons including:
- The patient’s underlying disease for which transplant was warranted
- The drugs and radiation used to prepare patients for transplant
- The transplant itself
- Immunosuppressive drugs taken after the transplant
It is important patients and families understand the need for revaccination to prevent infectious diseases. Revaccination after transplant is necessary to restore the protection from certain infectious diseases such as polio, measles, mumps, rubella and hepatitis B.
Revaccination requirements can be complex, and the vaccines need to be administered in a particular order, following a prescribed schedule to minimize risk of disease for these vulnerable patients.
Our clinical providers have found that relying on the patients’ primary care team to administer these vaccinations is not always the most effective way to provide this post-transplant care. Most primary care practices see small numbers of post-BMT patients and are unfamiliar with a post-BMT revaccination schedule, as it is more concentrated than a routine vaccination schedule for new babies and children.
What the Revaccination Clinic does
We offer patients the option to receive their vaccines in our follow-up clinic, which is the first clinic of its kind in the country. Patients are revaccinated using the best practice standards developed by our BMT clinicians in consult with specialists in Immunology, Infectious Diseases and Pharmacy.
