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.

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Last Medical Review: February 12, 2019 Last Revised: February 12, 2019

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