Childhood Leukemia

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Early Detection, Diagnosis, and Staging TOPICS

How is childhood leukemia classified?

Classification of the leukemia plays a major role in determining both treatment options and a child’s outlook (prognosis). Determining its type (acute lymphocytic, acute myeloid, etc.) and subtype 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?”.

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. 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 is 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 the leukemia cells in the central nervous system. 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

Doctors have found that cytogenetic tests, flow cytometry, and other lab tests provide more detailed information about 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

There are 4 main subtypes of ALL, as shown in the table below:



    Early Pre-B cell


    Pre-B cell


    Mature B cell


    T cell


B-cell ALL: About 85% of children with ALL have B-cell ALL.

  • The most common subtype of B-cell ALL is “early precursor B” (early pre-B) ALL.
  • The “pre-B” form of ALL accounts for 20% to 25% of patients with B-cell ALL.
  • Mature B-cell leukemia accounts for about 2% to 3% of childhood ALL. It is also called Burkitt leukemia. This disease is essentially the same as Burkitt lymphoma and is treated differently from most leukemias. It’s discussed in detail in our document, Non-Hodgkin Lymphoma in Children.

T-cell ALL: About 15% to 18% 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 involved and how mature it is. In this system, the subtypes of AML are classified mainly based on their morphology (how they look under the microscope) using routine and cytochemical stains. There are 8 subtypes of AML: M0 to M7 (the M refers to myeloid).

  • M0: This subtype of AML is made up of very immature cells – so immature that they can’t be labeled according to the types of cells listed above. This subtype can only be distinguished from ALL by flow cytometry, because the cells lack any distinct features that can be seen by microscope. (Flow cytometry is explained in the section, “How is childhood leukemia diagnosed?”) This type of leukemia is very rare in children.
  • M1: This subtype is made up of immature myeloblasts. It can be recognized by the way the cells look under the microscope after using cytochemical stains.
  • M2: This subtype is composed of slightly more mature forms of myeloblasts. It is the most common subtype of AML in children, making up a little more than 1 out of every 4 cases.
  • M3: The M3 subtype is also known as acute promyelocytic leukemia (APL). It is made up of promyelocytes, which are a more mature form of myeloblast. Treatment of APL is different than for other subtypes of AML, as it involves some newer drugs.
  • M4: This subtype is known as acute myelomonocytic leukemia. The cells are an early form of monoblast. The M4 subtype is more common in children less than 2 years of age.
  • M5: This is known as acute monocytic leukemia. It is made up of monoblasts. Like the M4 subtype, it is more common in children less than 2 years of age.
  • M6: This subtype of AML is known as acute erythroblastic leukemia (or acute erythroleukemia). It starts in erythroblasts, the cells that normally mature into red blood cells. It is very rare in children.
  • M7: This subtype is also known as acute megakaryoblastic leukemia. The cells are megakaryoblasts, which normally mature into megakaryocytes (the 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 other prognostic factors that doctors have learned about in recent years, such as chromosome changes in the leukemia cells. The newer WHO system includes some of these factors to try to help better classify cases of AML based on a person’s outlook. Not all doctors use this new system.

The WHO 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)

Hybrid or mixed lineage leukemias

These leukemias have cells with features of both ALL and AML when they are subjected to lab tests. In children, these leukemias are generally treated like ALL and 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, 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)

Bone marrow and/or blood samples from a patient in this phase 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 may 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.

Last Medical Review: 10/24/2013
Last Revised: 02/03/2014