Classifying AML

Classification of Acute Myeloid Leukemia

There are many subtypes of acute myeloid leukemia (AML), and the disease is further grouped by treatment status, response to treatment, and likelihood of doing well on standard therapy. This last factor, called risk stratification, is based on the cytogenetic (chromosomal) and molecular abnormalities associated with your disease. Your doctors use this information to plan your treatment and predict the outcome.

Subtypes of AML

AML is divided into subtypes based on the maturity of the leukemic cells at diagnosis, how different they are from normal cells, and the chromosomal features of the disease. Chromosome abnormalities are detected in most cases of adult AML. In fact, there are so many different types of chromosome abnormalities in AML that it is often considered a group of related diseases, rather than a single disease.

Anna Robinson, AML Survivor

Anna Robinson, AML Survivor Diagnosed with AML with the FLT3 mutation, Anna Robinson received transfusions as supportive care before being treated with chemotherapy and two bone marrow transplants—one from her sister and one from an unrelated donor—at SCCA. Read more about Anna.

AML is categorized into the following subtypes, and each of these may be further split into additional groups.

  • AML with characteristic cytogenetic abnormalities
  • AML with mutations of the FLT3, NPM1, or CMBPA gene
  • AML with multilineage dysplasia
  • Therapy-related AML and myelodysplastic syndromes (applies to people who have received chemotherapy or radiation therapy for another type of malignancy—up to 20 percent of people with AML)
  • AML not otherwise categorized
  • Acute leukemias of ambiguous lineage

Acute Promyelocytic Leukemia

One particularly aggressive subtype of AML with characteristic genetic abnormalities is acute promyelocytic leukemia (APL). APL is characterized by a translocation of the PML gene on chromosome 15 and the RARα gene on chromosome 17—denoted as t(15;17). This subtype accounts for about 10 percent of all cases of AML. It usually occurs in middle-aged adults and is seen more frequently in people of Hispanic descent and in people who are obese. Treatment for APL  is different than for AML.

AML Treatment Status and Response to Treatment

Most cancers are assigned a numbered stage based on the size of the tumor and how far it has spread. Because leukemia doesn’t typically form a solid tumor and is found throughout the body when it is diagnosed, there is no formal staging system for AML. Instead it is described as:

  • Newly diagnosed/untreated
  • In remission
  • Relapsed/refractory

Newly Diagnosed/Untreated AML

Newly diagnosed AML is described as untreated. Treatment may have begun for relief of symptoms, such as fever and bleeding, but treatment has not begun for the leukemia. Diagnosis has confirmed all of the following:

  • The complete blood count (CBC) is abnormal.
  • Greater than 20 percent of bone marrow or blood cells are leukemia cells.
  • Signs and symptoms of leukemia are present.

AML in Remission

After treatment, people with AML may be considered in remission if all of the following are true:

  • CBC is normal.
  • Leukemia cells present in the bone marrow are limited to 5 percent or less, although minimal residual disease (MRD) may be present.
  • No signs or symptoms of leukemia are evident anywhere in the body.

Relapsed/Refractory AML

AML that returns after going into remission is called relapsed or recurrent. It may come back in the blood, the bone marrow, or both. Refractory means the leukemia has not entered remission.

AML Risk Stratification

Risk stratification is used to estimate the probability of success with standard therapy. You and your treatment team may use this information to determine whether you should be treated with standard therapy or if an investigational treatment available in a clinical study, or clinical trial, may be your best option.

Newly Diagnosed/Untreated Patients

In newly diagnosed/untreated patients, several risk groups are recognized.

  • Favorable risk: This includes people with certain genetic abnormalities—translocation between chromosomes 8 and 21, or translocation between chromosomes 15 and 17 (APL), or inversion on chromosome 16—or with a mutation of the NPM1 gene but not the FLT3 gene. People with favorable-risk AML are generally treated with standard therapy. Some older patients (over 60) may be treated with a bone marrow transplant.
  • Adverse risk: This includes most people who have cytogenetic abnormalities other than those in the favorable-risk group or who have the FLT3 mutation. Typically the best treatment option for people with adverse-risk AML is a clinical study or bone marrow transplant.
  • Intermediate risk: This includes people with normal cytogenetics who do not fall into the other two risk groups. Depending on the specifics of the disease, standard therapy, bone marrow transplant, or a clinical study may all be treatment options.

People Whose AML Recurs After Initial Remission

The treatment options and prognosis of people whose AML recurs after treatment with standard therapy mainly depend on the duration of their initial remission. If initial remission lasted two years or more, they fall into the intermediate-risk group. If the duration of initial remission was less than two years, they fall into the adverse-risk group.

Post-treatment Information

The above risk stratification is based on pre-treatment information. It is becoming clear that for people in remission prognosis is heavily dependent on the presence of MRD as assessed by flow cytometry or polymerase chain reaction. For example, if a person was in the intermediate-risk group before treatment, then after treatment he or she might fall into the favorable-risk group if there’s no MRD but into the adverse-risk group if there is MRD.