How Is Childhood Leukemia Classified?

The type of leukemia a child has plays a major role in both treatment options and the child’s outlook (prognosis). Determining the type (acute lymphocytic, acute myeloid, etc.) and subtype of the leukemia is done by testing samples of the blood, bone marrow, and sometimes lymph nodes or cerebrospinal fluid (CSF), as described in How Is Childhood Leukemia Diagnosed?

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. But leukemia is not staged like most other cancers. It starts in the bone marrow and quickly spreads to the blood, so leukemia cells are already scattered throughout the body.

Still, it’s important to know whether the leukemia cells have started to collect in other organs such as the liver, spleen, lymph nodes, testicles, or central nervous system (brain and spinal cord). For instance, if the leukemia cells have spread to the central nervous system in large numbers, they will be seen in samples of CSF. Treatment must be more intense to kill these leukemia cells. This is why a spinal tap (lumbar puncture) is done as part of the early diagnostic testing.

Acute lymphocytic (lymphoblastic) leukemia (ALL)

Acute lymphocytic leukemia (ALL) is a fast-growing cancer of lymphocyte-forming cells called lymphoblasts.

Classification based on how the leukemia cells look (morphology)

In the past, doctors used the French-American-British (FAB) classification to divide ALL into 3 major groups (L1, L2, or L3) based on how the cells looked under the microscope. Some doctors may still refer to these categories. But newer lab tests now let doctors classify ALL based on more than just how the cells look under the microscope.

Classification based on immunophenotype

Newer types of lab tests can help determine the subtype of ALL and the patient’s prognosis. These tests help divide ALL into groups based on the immunophenotype of the leukemia, which takes into account:

  • The type of lymphocyte (B cell or T cell) the leukemia cells come from
  • How mature these leukemia cells are

B-cell ALL: In about 80% to 85% of children with ALL, the leukemia starts in B cells. There are several subtypes of B-cell ALL:

  • Early precursor B (early pre-B) ALL (also called pro-B ALL)
  • Common ALL
  • Pre-B ALL
  • Mature B-cell ALL (also called Burkitt leukemia). This type is rare, accounting for only about 2% to 3% of childhood ALL. It is essentially the same as Burkitt lymphoma and is treated differently from most leukemias. It’s discussed in detail in Non-Hodgkin Lymphoma in Children.

T-cell ALL: About 15% to 20% of children with ALL have T-cell ALL. This type of leukemia affects boys more than girls and generally affects older children more than does B-cell ALL. It often causes an enlarged thymus (a small organ in front of the windpipe), which can sometimes cause breathing problems. It may also spread to the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) early in the course of the disease.

Aside from the subtype of ALL, other factors are important in determining outlook (prognosis). These are described in the section Prognostic Factors in Childhood Leukemia.

Acute myelogenous leukemia (AML)

Acute myelogenous leukemia (AML) is typically a fast-growing cancer of one of the following types of early (immature) bone marrow cells:

  • Myeloblasts: These cells normally form white blood cells called granulocytes (neutrophils, eosinophils, and basophils).
  • Monoblasts: These cells normally become white blood cells called monocytes and macrophages.
  • Erythroblasts: These cells mature into red blood cells.
  • Megakaryoblasts: These cells normally become megakaryocytes, the cells that make platelets.

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

French-American-British (FAB) classification of AML

The older FAB system divides AML into subtypes based on the type of cell the leukemia started in and how mature the cells are. In this system, the subtypes of AML are classified mainly based on their morphology (how they look under the microscope). There are 8 subtypes of AML: M0 to M7 (the M refers to myeloid).

  • M0: Undifferentiated acute myeloblastic leukemia
  • M1: Acute myeloblastic leukemia with minimal maturation
  • M2: Acute myeloblastic leukemia with maturation (the most common subtype of AML in children)
  • M3: Acute promyelocytic leukemia (APL)
  • M4: Acute myelomonocytic leukemia (more common in children less than 2 years of age)
  • M5: Acute monocytic leukemia (more common in children less than 2 years of age)
  • M6: Acute erythroid leukemia
  • M7: Acute megakaryoblastic leukemia

Subtypes M0 through M5 all start in immature forms of white blood cells. M6 AML starts in 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 still commonly used to group AML into subtypes. But it doesn’t take into account many other factors that are now known to affect prognosis (outlook), such as chromosome changes in the leukemia cells. The newer WHO system includes some of these factors to help better classify AML based on a person’s outlook.

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). These are also known as mixed phenotype or mixed lineage leukemias. In children, these leukemias are generally treated like ALL and usually respond to treatment like ALL.

Chronic myelogenous leukemia (CML)

Chronic myelogenous leukemia (CML) is typically a slower-growing cancer of early (immature) myeloid bone marrow cells. CML is not common in children, but it can occur.

The course of CML is divided into 3 phases, based mainly on the number of immature white blood cells – myeloblasts (“blasts”) – that are seen in the blood or bone marrow. Different groups of experts have suggested slightly different cutoffs to define the phases, but a common system (proposed by the World Health Organization) is described below.

If the leukemia is not cured with treatment, it can progress to more advanced phases over time.

Chronic phase

This is the earliest phase, in which patients typically have less than 10% blasts in their blood or bone marrow samples. These children usually have fairly mild symptoms (if any), and the leukemia usually responds well to standard treatments. Most patients are in the chronic phase when they are diagnosed.

Accelerated phase

Patients are considered to be in accelerated phase if bone marrow or blood samples have more than 10% but fewer than 20% blasts, or if levels of certain other blood cells are too high or too low.

Children whose CML is in accelerated phase may have symptoms such as fever, night sweats, poor appetite, and weight loss. CML in the accelerated phase might not respond as well to treatment as CML in the chronic phase.

Blast phase (also called acute phase or blast crisis)

In this phase, bone marrow and/or blood samples have more than 20% blasts. The blast cells often spread to tissues and organs beyond the bone marrow. These children often have fever, poor appetite, and weight loss. At this point the CML acts much like an aggressive acute leukemia (AML or, less often, ALL).

Not all doctors agree with or follow these cutoff points for the different phases. If you have questions about what phase your child’s CML is in, be sure to have the doctor explain it to you.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: April 17, 2015 Last Revised: February 3, 2016

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