How is acute lymphocytic leukemia classified?

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.

Acute lymphocytic leukemia (ALL), on the other hand, does not usually form tumor masses. It generally affects all of the bone marrow in the body and, in many cases, may have spread to other organs, such as the liver, spleen, and lymph nodes. Therefore the outlook for the patient with ALL depends on other information, such as the subtype of ALL (determined by lab tests), the age of the patient, and other lab test results.

Different systems have been used to classify ALL into subtypes.

The French-American-British (FAB) classification

In the 1970s, a group of French, American, and British (FAB) leukemia experts divided ALL into 3 subtypes (L1, L2, and L3), based on the way the leukemia cells looked under the microscope after routine staining. This system has largely been replaced, as newer lab tests now allow doctors to classify ALL more accurately.

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

These groups have largely replaced the FAB classification. The subtypes of ALL are now named as follows:

B-cell ALL

• Early pre-B ALL (also called pro-B ALL) – about 10% of cases
• Common ALL – about 50% of cases
• Pre-B ALL – about 10% of cases
• Mature B-cell ALL (Burkitt leukemia) – about 4% of cases

T-cell ALL

• Pre-T ALL – about 5% to 10% of cases
• Mature T-cell ALL – about 15% to 20% of cases

The subtypes of ALL each carry a slightly different outlook (prognosis), but other factors (like gene changes in the leukemia cells) may also have an impact. Some of these prognostic factors are listed in the next section.

Mixed lineage acute leukemias

In recent years, newer lab tests have shown that a small number of acute leukemias actually have both lymphocytic and myeloid features. Sometimes the leukemia cells have both myeloid and lymphocytic traits in the same cells. In other cases, a patient may have some leukemia cells with myeloid features and others with lymphocytic features. These types of leukemias may be called mixed lineage leukemia, ALL with myeloid markers (My+ ALL), AML with lymphoid markers, or biphenotypic acute leukemia (BAL).

Most studies suggest these leukemias tend to have a poorer outlook than standard subtypes of ALL or AML. Not all doctors agree on the best way to treat these leukemias. Intensive treatment (such as a stem cell transplant) is often used when possible, as there is a high risk of recurrence after treatment.

Prognostic factors

As leukemia treatment has improved over the years, research has focused on why some patients have a better chance for cure than others. Differences among patients that affect response to treatment are called prognostic factors. They help doctors decide if people with a certain type of leukemia should get more or less treatment.

• Age: Younger patients tend to have a better prognosis than older patients. There is no set cutoff for this, but generally those younger than 50 do better than those in their 50s, while people in their 50s do better than those in their 60s or older.
• Initial white blood cell count: People with a lower WBC count (less than 30,000 for B-cell ALL and less than 100,000 for T-cell ALL) at the time of diagnosis tend to have a better prognosis.
• ALL subtype: In general, T-cell ALL has a better prognosis, while mature B-cell ALL (Burkitt leukemia) has a poorer prognosis. Other subtypes of B-cell ALL fall somewhere in between. It's important to note that this doesn't apply to all cases. For instance, some subtypes of T-cell ALL have a better outlook than others.
• Chromosome abnormalities: The presence of Philadelphia chromosome (a translocation between chromosomes 9 and 22) predicts a poorer prognosis. The same is true of a translocation between chromosomes 4 and 11. An extra chromosome 8 or a missing chromosome 7 also predicts a poorer outlook.
• Response to chemotherapy: Patients who achieve a complete remission (no evidence of leukemia remaining) within 4 to 5 weeks of starting treatment tend to have a better prognosis than those in whom this takes longer. Patients who don't achieve a complete remission at all have a poorer outlook. The prognostic value of minimal residual disease (described below) is still being studied.

Status of acute lymphocytic leukemia after treatment

How well leukemia responds to treatment has an effect on the patient's long-term chance for recovery.

A remission (complete remission) is usually defined as having no evidence of leukemia 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 lab tests, such as PCR. Even when leukemia is in remission, this does not always mean that it has been cured.

Minimal residual disease (MRD) is a term used after treatment when leukemia cells can't be found in the bone marrow using standard lab tests (such as looking at cells under a microscope), but they can still be detected with more sensitive tests (such as flow cytometry or PCR). Patients with MRD after treatment are more likely to have their leukemia relapse (come back after treatment) and overall have a poorer outlook than those who achieve a complete remission. Doctors are looking to see if these patients may benefit from further or more intensive treatment.

Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has relapsed (come back) after treatment. For a patient to be in relapse, more than 5% of the bone marrow must be made up of blast cells.