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Acute Lymphocytic Leukemia (ALL) Subtypes and Prognostic Factors

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. This can be helpful in predicting a person’s outlook and deciding on treatment.

Acute lymphocytic leukemia (ALL), on the other hand, does not usually form tumors. It generally affects all of the bone marrow in the body and, in some cases, has already spread to other organs, such as the liver, spleen, and lymph nodes, by the time it is found. Therefore ALL is not staged like most other cancers. The outlook for a person with ALL depends on other information, such as the subtype of ALL (determined by lab tests), the patient's age, and other lab test results.

Subtypes of Acute Lymphocytic Leukemia (ALL)

Different systems have been used to classify ALL into subtypes.

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, known as the FAB classification, has largely been replaced, as newer lab tests now allow doctors to classify ALL more accurately.

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 gene and chromosome changes in the leukemia cells.

The World Health Organization (WHO) system, most recently updated in 2016, includes some of these factors to try to better classify ALL. The WHO system divides ALL into several groups:

B-cell ALL

B-cell ALL with certain genetic abnormalities (gene or chromosome changes)

  • B-cell ALL with hypodiploidy (the leukemia cells have fewer than 44 chromosomes [normal cells have 46])
  • B-cell ALL with hyperdiploidy (the leukemia cells have more than 50 chromosomes)
  • B-cell ALL with a translocation between chromosomes 9 and 22 [t(9;22)] (the Philadelphia chromosome, which creates the BCR-ABL1 fusion gene)
  • B-cell ALL with a translocation between chromosome 11 and another chromosome
  • B-cell ALL with a translocation between chromosomes 12 and 21 [t(12;21)]
  • B-cell ALL with a translocation between chromosomes 1 and 19 [t(1;19]
  • B-cell ALL with a translocation between chromosomes 5 and 14 [t(5;14)]
  • B-cell ALL with amplification (too many copies) of a portion of chromosome 21 (iAMP21)*
  • B-cell ALL with translocations involving certain tyrosine kinases or cytokine receptors (also known as “BCR-ABL1–like ALL”)*

 B-cell ALL, not otherwise specified

T-cell ALL

  • Early T-cell precursor lymphoblastic leukemia*

* It's not yet clear if there's enough evidence that it's a unique group (meaning it is still a "provisional entity")

Mixed lineage acute leukemias

A small number of acute leukemias 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, acute undifferentiated leukemia, or, or mixed phenotype acute leukemia (MPAL).

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.

Prognostic factors for ALL

As leukemia treatment has improved over the years, research has focused on why some people have a better chance for cure than others. Different factors that affect a person's prognosis (outlook) are called prognostic factors. They can help doctors decide if people with a certain type of leukemia should get more or less treatment.

Age

Among adults, 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.

Some of this might be because older patients are more likely to have unfavorable chromosome abnormalities (see below). Older patients are also more likely to have other medical conditions that can make it harder to treat them with more intense chemotherapy regimens.

Initial white blood cell (WBC) count

People with a lower WBC count (less than 30,000 for B-cell ALL and less than 100,000 for T-cell ALL) when they are first diagnosed tend to have a better prognosis.

Gene or chromosome abnormalities

Whether the leukemia cells have certain changes in their genes or chromosomes can affect prognosis. For example, patients tend to have a poorer outcome if the leukemia cells have:

  • The Philadelphia chromosome (a translocation between chromosomes 9 and 22), although this outlook has improved with modern targeted therapy drugs
  • A translocation between chromosomes 4 and 11
  • A translocation involving chromosome 14
  • Amplification (too many copies) of part of chromosome 21
  • Fewer than 44 chromosomes (hypodiploidy)
  • 5 or more chromosome changes (complex karyotype)

On the other hand, people tend to have a better outlook if the leukemia cells have:

  • A translocation between chromosomes 12 and 21
  • More than 50 chromosomes (hyperdiploidy)

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 presence of minimal residual disease (described below) after initial treatment also seems to affect prognosis, although this is still being studied.

Status of ALL during and after treatment

How well leukemia responds to treatment affects the patient’s long-term chance for recovery.

Remission

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 complete molecular remission means there is no evidence of leukemia cells in the bone marrow, 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.

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 studying if these patients could benefit from further or more intensive 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.

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.

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.

Jain N, Gurbuxani S, Rhee C, Stock W. Chapter 65: Acute Lymphoblastic Leukemia in Adults. In: Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa: Elsevier; 2013.

National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia. V.1.2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/all.pdf on July 23, 2018.

Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: A comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577.

Last Revised: October 17, 2018

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