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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.

But ALL (acute lymphocytic leukemia, also known as acute lymphoblastic leukemia) doesn’t usually form tumors. It is generally widespread throughout the bone marrow and blood. Sometimes it has already spread to other organs, such as the liver, spleen, and lymph nodes, by the time it is found.

Because of this, ALL isn’t 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)
  • Certain prognostic factors, such as a person’s age and other lab test results

In turn, these can often be used to help guide treatment.

Subtypes of acute lymphocytic leukemia (ALL)

The ALL subtypes are based mainly based on the results of lab tests of the leukemia cells, such as cytogenetic tests, flow cytometry, and fluorescent in situ hybridization (FISH). These tests help divide ALL into groups based on the gene and chromosome changes in the leukemia cells.

Two main systems can be used to classify ALL into subtypes:

  • World Health Organization (WHO) classification
  • International Consensus Classification (ICC)

These systems are alike in many ways, although there are some small differences. Either system can be used, but some doctors might prefer one over the other.

The subtypes below are those listed in the WHO classification system. This system considers ALL and lymphoblastic lymphoma (LBL) to be different versions of the same disease (see What Is Acute Lymphocytic Leukemia), so it describes each subtype as a lymphoblastic leukemia/lymphoma.

These leukemias start in early forms of B lymphocytes (B cells). They are grouped mainly by certain gene or chromosome changes (if any) in the leukemia cells.

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

  • B-lymphoblastic leukemia/lymphoma with high hyperdiploidy (the leukemia cells have more than 50 chromosomes [normal cells have 46])
  • B-lymphoblastic leukemia/lymphoma with hypodiploidy (the leukemia cells have fewer than 44 chromosomes)
  • B-lymphoblastic leukemia/lymphoma with iAMP21 (amplification, or too many copies, of a portion of chromosome 21)
  • B-lymphoblastic leukemia/lymphoma with a BCR::ABL1 fusion gene
  • B-lymphoblastic leukemia/lymphoma with BCR::ABL1-like features
  • B-lymphoblastic leukemia/lymphoma with a KMT2A gene rearrangement
  • B-lymphoblastic leukemia/lymphoma with an ETV6::RUNX1 fusion gene
  • B-lymphoblastic leukemia/lymphoma with ETV6::RUNX1-like features
  • B-lymphoblastic leukemia/lymphoma with a TCF3::PBX1 fusion gene
  • B-lymphoblastic leukemia/lymphoma with an IGH::IL3 fusion gene
  • B-lymphoblastic leukemia/lymphoma with a TCF3::HLF fusion gene
  • B-lymphoblastic leukemia/lymphoma with other defined genetic abnormalities

B-lymphoblastic leukemia/lymphoma, not otherwise specified (NOS)

These leukemias start in early forms of T lymphocytes (T cells). T-cell ALL is less common than B-cell ALL.

  • Early T-precursor lymphoblastic leukemia/lymphoma
  • T-lymphoblastic leukemia/lymphoma, not otherwise specified (NOS)

In a small number of acute leukemias, the leukemia cells have both myeloid and lymphocytic traits in the same cells. These may also be called bilineage leukemia or biphenotypic acute leukemia.

MPAL is rare, so it’s been hard to study. Most studies suggest these leukemias tend to be harder to treat than standard subtypes of ALL or AML. Not all doctors agree on the best way to treat them. There is a high risk of recurrence after treatment, so intensive treatment (such as a stem cell transplant) is often used when possible.

Prognostic factors for ALL

The subtype of ALL can be important in determining a person's prognosis (outlook) and treatment options. But other factors can also affect why some people with ALL tend to have a better outlook than others. These are called prognostic factors.

Prognostic factors help doctors determine a person's risk of the leukemia coming back after treatment, and therefore whether they should get more or less intensive treatment.

Age

Among adults, younger patients tend to have a better prognosis than older patients.

There is no set cutoff for this, but generally:

  • People younger than 50 do better than those in their 50s.
  • 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 people are also more likely to have other medical conditions that make it harder to treat them with more intense chemotherapy regimens.

Initial white blood cell (WBC) count

People with a lower WBC count at the time of diagnosis tend to have a better outlook. This is defined as:

  • Less than 30,000 for B-cell ALL
  • Less than 100,000 for T-cell ALL

Gene or chromosome abnormalities

Certain changes in the genes or chromosomes of  leukemia cells can affect a person’s prognosis.

People tend to have a poorer outlook if the leukemia cells have:

  • A translocation between chromosomes 4 and 11 (resulting in an altered KMT2A gene)
  • A TP53 gene mutation
  • A change in certain other genes, including IGH, HLF, ZNF384, MEF2D, MYC, and IKZF1
  • Amplification (too many copies) of part of chromosome 21
  • Fewer than 44 chromosomes (hypodiploidy)
  • 5 or more chromosome changes (complex karyotype)

People tend to have a better outlook if the leukemia cells have:

  • A translocation between chromosomes 12 and 21 (resulting in an ETV6::RUNX1 fusion gene)
  • A translocation between chromosomes 1 and 19 (resulting in a TCF3::PBX1 fusion gene)
  • More than 50 chromosomes (hyperdiploidy), especially if there are extra copies of chromosomes 4, 10, or 17

Response to initial treatment

People whose ALL goes into a complete remission within 4 to 5 weeks of starting treatment tend to have a better prognosis than those for whom this takes longer, or those whose ALL does not go into remission.

  • Complete remission: no visible leukemia in the bone marrow (see below)

The presence of minimal residual disease (MRD, 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 ALL responds to treatment affects a person’s long-term chance for recovery.

Remission and minimal/measurable residual disease (MRD)

A remission is usually defined as having no evidence of leukemia after the initial round of treatment (induction).

Types of remission

  • A complete remission (CR) means there are no lymphoblasts (ALL cells) in the blood, the bone marrow contains fewer than 5% blast cells (the normal percentage), blood cell counts are within normal limits, and there are no signs of leukemia in other parts of the body.
  • A complete remission with partial hematologic recovery (CRh) is similar to a CR, except the number of platelets and neutrophils (a type of white blood cell) has not quite returned to normal.
  • A complete remission with incomplete hematologic recovery (CRi) is similar to a CR, except that either the number of platelets or the number of neutrophils has not returned to normal.

Very sensitive lab tests such as next generation sequencing (NGS), high-sensitivity flow cytometry, or polymerase chain reaction (PCR) are typically done on bone marrow samples after the initial treatment, even if there’s no evidence of leukemia cells in standard lab tests.

These sensitive tests can detect even very small numbers of leukemia cells in a sample. See Tests for ALL to learn more about them.

A complete molecular remission (CMR) means there is no evidence of leukemia cells in the bone marrow, even when using very sensitive lab tests.

Minimal residual disease (MRD), also known as measurable residual disease, 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
  • Can still be detected with more sensitive tests

People with MRD after initial treatment are more likely to have the leukemia relapse (come back) and overall tend to have a poorer outlook than those who achieve a complete molecular remission. Doctors are studying whether these patients could benefit from further or more intensive treatment.

Leukemia that is not in remission

ALL that isn’t in remission might be described in different ways:

  • Refractory (resistant) disease means the leukemia did not go into complete remission after initial treatment (induction).
  • Progressive disease means the number of leukemia cells in the blood or bone marrow is rising, and/or the leukemia has now spread to another part of the body.
  • Relapsed disease means the leukemia has come back after a complete remission. This could be the appearance of blasts in the blood or in another part of the body, or more than 5% of the bone marrow made up of blasts.

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Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).

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Last Revised: August 13, 2025

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