Leukemia--Acute Myeloid (Myelogenous)

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Early Detection, Diagnosis, and Staging TOPICS

How is acute myeloid leukemia classified?

Most types of cancers are assigned numbered stages to describe their extent in the body, based on the size of the tumor and how far the cancer has spread.

Acute myeloid leukemia (AML), on the other hand, does not usually form tumor masses. It generally involves all of the bone marrow in the body and, in some cases, may have spread to other organs, such as the liver and spleen. Therefore the outlook for the patient with AML depends on other information, such as the subtype of AML (determined by lab tests), the age of the patient, and other lab test results.

Two systems have been used to classify AML into subtypes – the French-American-British (FAB) classification and the newer World Health Organization (WHO) classification.

The French-American-British (FAB) classification of AML

In the 1970s, a group of French, American, and British leukemia experts divided acute myeloid leukemias into subtypes, M0 through M7, based on the type of cell from which the leukemia developed and how mature the cells are. This was based largely on how the leukemia cells looked under the microscope after routine staining.

    FAB subtype

    Name

    M0

    Undifferentiated acute myeloblastic leukemia

    M1

    Acute myeloblastic leukemia with minimal maturation

    M2

    Acute myeloblastic leukemia with maturation

    M3

    Acute promyelocytic leukemia (APL)

    M4

    Acute myelomonocytic leukemia

    M4 eos

    Acute myelomonocytic leukemia with eosinophilia

    M5

    Acute monocytic leukemia

    M6

    Acute erythroid leukemia

    M7

    Acute megakaryoblastic leukemia

Subtypes M0 through M5 all start in precursors of white blood cells. M6 AML starts in very early forms of red blood cells, while M7 AML starts in early forms of cells that make platelets.

Some subtypes of AML defined in the FAB system are linked with certain symptoms. For example, bleeding or blood clotting problems are often a problem for patients with the M3 subtype of AML, also known as acute promyelocytic leukemia (APL).

Identifying APL is very important for 2 reasons. First, certain complications of APL can often be prevented by appropriate treatment. Second, APL is treated differently from most other forms of AML – it responds to drugs like retinoids (drugs related to vitamin A).

World Health Organization (WHO) classification of AML

The FAB classification system is useful and is still commonly used to group AML into subtypes. But it doesn’t take into account many of the factors that are known to impact prognosis (outlook). In 2001, the World Health Organization (WHO) published a newer system that includes some of these factors to try to help better classify cases of AML based on a patient’s outlook.

The WHO classification system divides AML into several broad groups:

AML with certain genetic abnormalities

  • AML with a translocation between chromosomes 8 and 21
  • AML with a translocation or inversion in chromosome 16
  • AML with changes in chromosome 11
  • APL (M3), which usually has translocation between chromosomes 15 and 17

AML with multilineage dysplasia (more than one abnormal myeloid cell type is involved)

AML related to previous chemotherapy or radiation

AML not otherwise specified (includes cases of AML that don’t fall into one of the above groups; similar to the FAB classification)

  • Undifferentiated AML (M0)
  • AML with minimal maturation (M1)
  • AML with maturation (M2)
  • Acute myelomonocytic leukemia (M4)
  • Acute monocytic leukemia (M5)
  • Acute erythroid leukemia (M6)
  • Acute megakaryoblastic leukemia (M7)
  • Acute basophilic leukemia
  • Acute panmyelosis with fibrosis
  • Myeloid sarcoma (also known as granulocytic sarcoma or chloroma)

Undifferentiated or biphenotypic acute leukemias (leukemias that have both lymphocytic and myeloid features). Sometimes called ALL with myeloid markers, AML with lymphoid markers, or mixed lineage leukemias.

Prognostic factors for acute myeloid leukemia

Leukemia treatment has improved over the years, so research has focused on why some patients have a better chance to be cured than others. Differences among patients that affect response to treatment are called prognostic factors. Prognostic factors help doctors decide if people with a certain type of leukemia should receive more or less treatment. Some of these include:

Chromosome abnormalities

Chromosome changes give one clue to prognosis. Not all patients have these abnormalities. Those listed below are the most common, but there are many others. Patients without any of these usually have an outlook that is between favorable and unfavorable.

Favorable abnormalities:

  • Translocation between chromosomes 8 and 21 (seen most often in patients with M2)
  • Inversion of chromosome 16 (seen most often in patients with M4 eos) or a translocation between chromosome 16 and itself
  • Translocation between chromosomes 15 and 17 (seen most often in patients with M3)

Unfavorable abnormalities:

  • Deletion (loss) of part of chromosome 5 or 7 (no specific AML type)
  • Translocation or inversion of chromosome 3
  • Translocation between chromosomes 6 and 9
  • Translocation between chromosomes 9 and 22
  • Abnormalities of chromosome 11 (at the spot q23)
  • Complex changes - those involving several chromosomes (no specific AML type)

Gene mutations

Newer tests allow doctors to find changes within specific genes on chromosomes. People who have certain gene mutations may have a better or worse outlook.

For instance, about 1 patient out of 3 with AML has a mutation in the FLT3 gene. These people tend to have a poorer outcome, but new drugs that target this abnormal gene are now being studied, which may lead to better outcomes.

On the other hand, people with changes in the NPM1 gene (and no other abnormalities) seem to have a better prognosis than people without this change. Changes in the CEBPA gene are also linked to a better outcome.

In the coming years, doctors will use newer lab tests to learn more about the underlying genetic defects that cause AML and how they can be used to predict a patient’s prognosis. These genetic defects might also form the basis for treating the leukemias.

Markers on the leukemia cells

If the leukemia cells have the CD34 protein and/or the P-glycoprotein (MDR1 gene product) on the surface, it is linked to a worse outcome.

Age

Older patients (over 60) generally do not fare as well as younger patients. Some of this may be because they are more likely to have unfavorable chromosome abnormalities. Older patients may also have other medical conditions that can make it harder to treat them with more intense chemotherapy regimens.

White blood cell count

A high white blood cell count (>100,000) at the time of diagnosis is linked to a worse outlook.

Prior blood disorders or cancers

Having a prior blood disorder such as a myelodysplastic syndrome is linked to a worse outcome.

Treatment-related AML

AML that develops after treatment for another cancer tends is linked to a worse outcome.

Infection

Having an active systemic (blood) infection at the time of diagnosis makes a poor outcome more likely.

Leukemia cells in the central nervous system

Leukemia that has spread to the area around the brain and spinal cord can be hard to treat, since most regular chemotherapy drugs don’t penetrate that area.

Status of acute myeloid leukemia after treatment

Not surprisingly, how well a leukemia responds to treatment also has an effect on long-term prognosis.

A remission (complete remission) is usually defined as having no evidence of disease after 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 tests, such as PCR (polymerase chain reaction).

Minimal residual disease is a term used after treatment when leukemia cells can’t be found in the bone marrow using standard tests (such as looking at cells under a microscope), but more sensitive tests (such as flow cytometry or PCR) find evidence that leukemia cells remain in the bone marrow.

Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has come back after treatment (relapsed). For a patient to be relapsed, they must have more than 5% blast cells present in the bone marrow.


Last Medical Review: 07/24/2013
Last Revised: 02/07/2014