How Is Acute Myeloid Leukemia Classified?
For most types of cancer, determining the stage (extent) of the cancer is very important. The stage is based on the size of the tumor and how far the cancer has spread. This can be helpful in predicting a person’s outlook and deciding on treatment.
Acute myeloid leukemia (AML), on the other hand, does not usually form tumors. It generally is in all of the bone marrow in the body and, in some cases, has spread to other organs, such as the liver and spleen. Therefore AML is not staged like most other cancers. The outlook for a person with AML depends instead on other information, such as the subtype of AML (determined by lab tests), the patient’s age, and other lab test results.
Knowing the subtype of AML can be very important, as it sometimes affects both a patient’s outlook and the best treatment. For example, the acute promyelocytic leukemia (APL) subtype is often treated using drugs that are different from those used for other subtypes of AML.
Two of the main systems that have been used to classify AML into subtypes are 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 AML into subtypes, M0 through M7, based on the type of cell from which the leukemia develops and how mature the cells are. This was based largely on how the leukemia cells looked under the microscope after routine staining.
Undifferentiated acute myeloblastic leukemia
Acute myeloblastic leukemia with minimal maturation
Acute myeloblastic leukemia with maturation
Acute promyelocytic leukemia (APL)
Acute myelomonocytic leukemia
Acute myelomonocytic leukemia with eosinophilia
Acute monocytic leukemia
Acute erythroid leukemia
Acute megakaryoblastic leukemia
Subtypes M0 through M5 all start in immature forms of white blood cells. M6 AML starts in very immature forms of red blood cells, while M7 AML starts in immature forms of cells that make platelets.
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 now known to affect prognosis (outlook). The World Health Organization (WHO) has developed a newer system that includes some of these factors to try to better classify AML.
The WHO system divides AML into several 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 a translocation between chromosomes 9 and 11
- APL (M3) with a translocation between chromosomes 15 and 17
- AML with a translocation between chromosomes 6 and 9
- AML with a translocation or inversion in chromosome 3
- AML (megakaryoblastic) with a translocation between chromosomes 1 and 22
AML with myelodysplasia-related changes
AML related to previous chemotherapy or radiation
AML not otherwise specified (This includes cases of AML that don’t fall into one of the above groups, and is similar to the FAB classification.)
- AML with minimal differentiation (M0)
- AML without 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)
Myeloid proliferations related to Down syndrome
Undifferentiated and biphenotypic acute leukemias (leukemias that have both lymphocytic and myeloid features). Sometimes called ALL with myeloid markers, AML with lymphoid markers, or mixed phenotype acute leukemias.
Prognostic factors for acute myeloid leukemia
In recent years, research has focused on why some patients have a better chance to be cured than others. Differences among patients (or their leukemias) that affect response to treatment are called prognostic factors. Prognostic factors help doctors decide if people with a certain type of AML should get more or less treatment. Some of these include:
AML cells can have many kinds of chromosome changes, some of which can affect a person’s prognosis. Those listed below are some of the most common, but there are many others. Not all patients have these abnormalities. Patients without any of these usually have an outlook that is between favorable and unfavorable.
- 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)
- 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)
People whose leukemia cells 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 these leukemias.
Markers on the leukemia cells
If the leukemia cells have the CD34 protein and/or the P-glycoprotein (MDR1 gene product) on their surface, it is linked to a worse outcome.
Older patients (over 60) generally don’t do as well as younger patients. Some of this may be because they are more likely to have unfavorable chromosome abnormalities. Older patients sometimes 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 disorder leading to AML
Having a prior blood disorder such as a myelodysplastic syndrome is linked to a worse outcome.
AML that develops after treatment for another cancer tends is linked to a worse outcome.
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 chemotherapy drugs can’t reach that area.
Status of acute myeloid leukemia after treatment
Not surprisingly, how well (and how quickly) the leukemia responds to treatment also affects long-term prognosis. Better responses have been linked with better long-term outcomes.
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 there are still leukemia cells 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 have relapsed, they must have more than 5% blast cells in their bone marrow.
Last Medical Review: December 9, 2014 Last Revised: February 22, 2016