Prognostic factors in childhood leukemia (ALL or AML)
Certain differences among patients that affect the leukemia’s response to treatment are called prognostic factors. They help doctors decide whether a child with leukemia should receive standard treatment or more intensive treatment. Prognostic factors seem to be more important in acute lymphocytic leukemia (ALL) than in acute myelogenous leukemia (AML).
Different systems are used to classify childhood ALL risk. In one of the more common systems, children with ALL are divided into standard-risk, high-risk, or very high-risk groups, with more intensive treatment given for higher risk patients. Generally, children at low risk have a better outlook than those at very high risk.
While all of the following are prognostic factors, only certain ones are used to determine which risk group a child falls into. (The first 2 factors – age at diagnosis and initial white blood cell count – are generally considered the most important.) It's important to know that many children with one or more poor prognostic factors can still be cured.
Age at diagnosis: Children with B-cell ALL between the ages of 1 and 9 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.
White blood cell (WBC) count: Children with ALL who have especially high WBC counts (greater than 50,000 cells per cubic millimeter) when they are diagnosed are classified as high risk and need more intensive treatment.
Subtype of ALL: Children with pre-B or early pre-B-cell ALL 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 do boys. As treatments have improved in recent years, this difference has shrunk.
Race/ethnicity: African-American and Hispanic children with ALL tend to have a lower cure rate than children of other races.
Spread to certain organs: Spread of the leukemia into the spinal fluid, or the testicles in boys, increases the chance of a poor outcome. Enlargement of the spleen and liver is usually linked to a high WBC count, but some doctors view this as a separate sign that the outlook is not as favorable.
Number of chromosomes: Patients 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 chromosomes than the normal 46 (hypodiploidy) have a less favorable outlook.
Chromosome translocations: Translocations result from the swapping of genetic material (DNA) between chromosomes. 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), 1 and 19, 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 treatment: Children whose leukemia responds completely (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. Children whose cancer does not respond may be given more intensive chemotherapy.
Prognostic factors for children with AML
Prognostic factors do not seem to be quite as important in predicting outcome for AML patients as they are for ALL.
Age at diagnosis: Children younger than age 2 with AML seem to do better than older children (especially teens), although the effect of age on outlook is not thought to be large.
White blood cell (WBC) count: Children with AML whose WBC count is less than 100,000 cells per cubic millimeter at diagnosis are cured more often 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.
Subtype of AML: Some subtypes of AML tend to have a better outlook than others. For example, the APL (M3) subtype tends to have a good outlook, while undifferentiated AML (M0) and acute megakaryoblastic leukemia (M7) are harder to treat effectively.
Cytogenetics: Children with leukemia cell 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 have a chromosomal defect known as monosomy 7 have a poorer prognosis. Monosomy 7 means that the leukemia cells have lost one of the copies of chromosome 7.
Morphology: The morphology of the AML cells (how they look under a microscope) may affect the patient's outlook for survival in some cases. Auer rods are rod-like or needle-shaped granules that can be seen inside some patients' AML cells. They are mostly seen in the cells of M2 and M3 types of AML and are usually linked with a good prognosis.
Myelodysplastic syndrome or secondary AML: Children who first have myelodysplastic syndrome ("smoldering leukemia") or whose leukemia is the result of treatment for another cancer tend to have a less favorable prognosis.
Response to 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 ALL or AML responds to the initial (induction) treatment has an effect on long-term prognosis.
A remission (complete remission) is usually defined as having no evidence of leukemia after the 4 to 6 weeks of induction treatment. This means the bone marrow contains fewer than 5% blast cells, the blood cell counts are within normal limits, and there are no signs or symptoms of the disease. A molecular complete remission means there is no evidence of leukemia cells in the bone marrow, even when using very sensitive lab tests, such as PCR. Even when leukemia is in remission, this does not always mean that it has been cured.
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). Details of testing for MRD may vary based on the type of leukemia and other factors. In general, children with detectable MRD during or after induction chemotherapy are more likely to have their leukemia relapse (come back) and may require more intense treatment. Children with more MRD have a greater risk of relapse than those with less MRD.
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 be in relapse, more than 5% of the marrow must be made up of blast cells.
Last Medical Review: 06/11/2012
Last Revised: 01/18/2013