1. The French-American-British (FAB) classification
The French-American-British (FAB) classification that was used commonly earlier includes:
- L1 – Around 25 to 30% of adult cases and 85% of childhood cases of ALL are of this subtype. In this type small cells are seen with:
- regular nuclear shape
- homogeneous chromatin
- small or absent nucleolus
- scanty cytoplasm
- L2 – Around 70% of adult cases and 14% of childhood cases are of this type. The cells are large and or varied shapes with:
- irregular nuclear shape
- heterogeneous chromatin
- large nucleolus
- L3 – This is a rarer subtype with only 1 to 2% cases. In this type the cells are large and uniform with vacuoles (bubble like features) in the cytoplasm overlying the nucleus.
2. 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:
- How mature these leukemia cells are
- The type of lymphocyte (B cell or T cell) the leukemia cells come from
a. B-cell Acute Lymphoblastic Leukaemia
- Common acute lymphoblastic leukaemia – about 50% of cases
- Early pre-B acute lymphoblastic leukaemia (also called pro-B acute lymphoblastic leukaemia) – about 10% of cases
- Mature B-cell acute lymphoblastic leukaemia (Burkitt leukemia) – about 4% of cases
- Pre-B acute lymphoblastic leukaemia – about 10% of cases
- Mature T-cell acute lymphoblastic leukaemia – about 15% to 20% of cases
- Pre-T acute lymphoblastic leukaemia – about 5% to 10% of cases
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 person 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 them. Intensive treatment (such as a stem cell transplant) is often used when possible, as there is a high risk of recurrence after treatment.
3. Prognostic factors
As leukemia treatment has improved over the years, research has focused on why some people have a better chance for cure than others. Differences in 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.
- 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 a translocation between chromosomes 4 and 11 in the leukemia cells predicts a poorer outlook, so does extra chromosome 8 or a missing chromosome 7. The presence of Philadelphia chromosome (a translocation between chromosomes 9 and 22) used to predict a poorer outlook, but not if modern targeted therapy drugs are used.
- 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.
- Response to chemotherapy. Patients who go into a complete remission (no visible leukemia in the bone marrow – see below) within 4 to 5 weeks of starting treatment tend to have a better prognosis than those for 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.
4. Status of acute lymphocytic leukemia after treatment
- Active disease. 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.
- Minimal residual disease. 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 the 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 could benefit from further or more intensive treatment.
- Remission. A remission (complete remission) is usually defined as the patient 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 no evidence of leukemia cells in the bone marrow is found, even when using very sensitive lab tests, such as polymerase chain reaction (PCR). Even when leukemia is in remission, this does not always mean that it has been cured.