Acute Myeloid Leukemia

How is Acute Myeloid Leukemia (AML) Classified?

Most types of cancers are assigned numbered stages, based on the size of the tumor and how far from the original site in the body the cancer has spread.

There is no need to stage leukemia, however, because leukemia already involves all the bone marrow in the body, and, in many cases, has also spread to other organs. Lab tests focus on determining the type and subtype of leukemia. This in turn determines the prognosis (outlook) of the specific disease, and helps predict which treatments will work best.

The French-American-British (FAB) Classification of Acute Myeloid Leukemias

Several years ago, an international conference of prominent hematologists/oncologists specializing in leukemia treatment and pathologists specializing in lab tests was held to decide on the best system of classification of acute leukemias. This group of French, American, and British doctors decided that acute myeloid leukemias should be divided into 8 subtypes, designated M0 through M7, based on the type of cell from which the leukemia developed.

French-American-British (FAB) Classification of AML

FAB Subtype	Name	Approximate % of adult AML patients	Prognosis compared to average for AML
M0	Undifferentiated AML	5%	Worse
M1	Myeloblastic leukemia with minimal maturation	15%	Average
M2	Myeloblastic leukemia with maturation	25%	Better
M3	Promyelocytic leukemia	10%	Best
M4	Myelomonocytic leukemia	20%	Average
M4 eos	Myelomonocytic leukemia with eosinophilia	5%	Better
M5	Monocytic leukemia	10%	Average
M6	Erythroid leukemia	5%	Worse
M7	Megakaryoblastic leukemia	5%	Worse

The original FAB system was based only on appearance of leukemic cells under the microscope after routine processing or cytochemical staining. More recently, doctors have found that cytogenetic studies, flow cytometry, and molecular genetic studies provide information that is more accurate in classifying AML and predicting the patient's prognosis. In the coming years we will learn more about the underlying genetic defects that cause leukemia. These defects, rather than the appearance of the cells under the microscope, will be used to classify leukemias and understand their prognoses. These genetic defects might also form the basis for treating the leukemias.

Some subtypes of AML defined in the FAB classification are associated 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.

Identifying M3 leukemia is very important for 2 reasons. The first is that these serious complications can often be prevented by appropriate treatment. The second reason is that M3 leukemias usually respond to retinoids (drugs chemically related to vitamin A).

Prognostic Factors

As leukemia treatment has improved over the past 20 years, research has focused on why some patients have a better chance of cure than others. Certain consistently observed differences among patients with good and poor responses to treatment are called prognostic factors and help doctors decide if a certain type of leukemia should receive more or less treatment.

These prognostic factors include the patient's age, white blood cell count, and cytogenetic test results. Other features considered are whether or not there was an existing preleukemic condition (myelodysplastic syndrome), or whether an earlier cancer was treated with chemotherapy and/or radiation therapy.

Chromosome abnormalities: Chromosome changes give us 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 abnormality usually have an outlook that is between favorable and unfavorable.

Favorable abnormalities:

• translocation between chromosomes 8 and 21 (seen in patients with M2)
• inversion of chromosome 16 (seen in patients with M4 eos)
• translocation between chromosomes 15 and 17 (seen in patients with M3)
Unfavorable abnormalities:

• deletion (loss) of part of chromosome 5 or 7 (no specific AML type)
• translocation between chromosomes 9 and 11 (seen in patients with M5)
• extra chromosome 8 (no specific AML type)

Genetic mutations: Although chromosome mutations (changes) are important, newer techniques allow doctors to find changes within specific genes on these chromosomes. One important gene is called NPM 1. People who have a mutation in this gene have a better outlook. Generally speaking they usually have favorable chromosome abnormalities or none at all.

Another mutation that affects outlook can happen in a gene called FLT3. About 30% of people with AML have changes in this gene. These people generally have a poor outcome, however, new drugs have been developed that target this abnormal gene and that may lead to better outcomes.

Age: Older patients (over 60) generally do not fare as well as younger patients.

White blood cell count: A high white blood cell count (>100,000) is linked to a worse outlook.

Prior conditions: Having a prior preleukemic condition or having AML that develops after treatment for another cancer has a worse prognosis.

Undifferentiated or Biphenotypic Acute Leukemias

More refined tests have shown that a number of acute leukemia cases have both lymphocytic and myeloid features. Sometimes leukemic cells have both myeloid and lymphocytic characteristics on the same cell. In other cases, a patient's leukemia may include some cells with myeloid features and other cells with lymphocytic features. Categorizing these leukemias is difficult and controversial. Sometimes these types of acute leukemias are called ALL with myeloid markers, AML with lymphoid markers, or biphenotypic (2-type) leukemias.

Status of Acute Myeloid Leukemia After Treatment

Adult AML is either classified as being in remission (with no evidence of disease after treatment—defined as fewer than 5% blasts in the bone marrow), or with active disease (with the patient either just newly diagnosed or in relapse).

Minimal residual disease is a term used when there is chemical evidence (either molecular or cytogenetic) that leukemic cells remain in the bone marrow, but there are not enough of these cells around to be found by routine examination under the microscope.

Relapse is the return of cancer after initial treatment. For a patient to be considered in relapse, he or she must have more than 5% blast cells present in the bone marrow.

American Cancer Society

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• Aplastic Anemia (AA)
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• Myelodysplastic Syndrome (MDS)
• Non-Hodgkin's Lymphoma (NHL)

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