Leukemia is a type of cancer that starts in the bone marrow and can move into the blood. Staging, or determining how advanced the cancer is, is important for choosing effective treatments. For most cancers, the stage depends on the size and location of tumors, as well how far the cancer has spread in the body.

Leukemia behaves differently from most cancer types. Since leukemia is a blood cancer, it doesn’t tend to form solid tumors. That also means that leukemia has usually spread throughout the body before diagnosis. Thus, the stages of leukemia differ from those of other types of cancer. Some types of leukemia have stages, but others are grouped into specific subtypes or classifications and don’t have stages.

Types of Leukemia

The many kinds of leukemia can be classified by how fast they develop and the types of cells involved. There are subtypes within each group. The four main types of leukemia are:

• Acute lymphoblastic leukemia (ALL)
• Acute myeloid leukemia (AML, also called acute myelogenous leukemia)
• Chronic lymphocytic leukemia (CLL)
• Chronic myeloid leukemia (CML, also called chronic myelogenous leukemia)

The names of the four main types come from the two types of cells affected — myeloid and lymphoid cells. Leukemia cells are immature white blood cells called blast cells. These blast cells develop certain genetic mutations (variants, or changes) that make the cells grow too fast. As the leukemia cells expand, they can crowd out other cell types like red blood cells and platelets. When there are too many leukemia cells and not enough of the other blood cells, normal body functions become disrupted. This means the body has trouble fighting infections, transporting oxygen, and clotting blood.

This imbalance of blood cells causes symptoms of leukemia, including:

• Weakness and fatigue
• Swollen lymph nodes
• Muscle aches
• Bone and joint pain
• Shortness of breath
• Weight loss
• Anemia (not enough red blood cells)
• Thrombocytopenia (poor blood clotting due to low platelets)
• Bruises
• Fever

Sometimes, leukemia cell numbers can get so high that they can clog blood vessels. This can cause serious vascular problems such as heart attack and stroke.

Acute Lymphocytic Leukemia Classification

There isn’t a standard staging system for ALL. Instead, ALL is grouped into subtypes based on characteristics of the leukemia cells. In the 1970s, a group of French, American, and British (FAB) researchers developed the FAB classification to categorize acute leukemias. This system relied on what leukemia cells looked like under a microscope, assigning subtypes L1, L2, or L3 based on cell size and shape.

Newer technology and tests now allow health care teams to better classify leukemia cells. The World Health Organization (WHO) released an updated ALL classification system in 2022.

The WHO system groups ALL based on which type of white blood cells become cancerous. These white blood cells, called B cells and T cells, play important roles in the immune system. B cells (also called B lymphocytes) make antibodies that help the body find and fight infections. T cells (T lymphocytes) have other jobs, such as killing infected cells, helping other immune cells work, and keeping the immune system balanced.

The WHO classifies ALL as:

• B-ALL — Cancerous B cells
• T-ALL — Cancerous T cells
• Acute leukemia of ambiguous lineage (ALAL) — Affects multiple types of white blood cells, with characteristics of both ALL and AML

Subtypes within these categories are based on specific genetic changes seen in the cells.

Acute Myeloid Leukemia Classification

The National Cancer Institute describes AML as untreated, in remission, or recurrent.

• Untreated AML is newly diagnosed and hasn’t been treated, except to relieve symptoms of leukemia. In untreated AML, at least 20 percent of the bone marrow cells are leukemia cells.
• When AML is in remission, there are no symptoms of leukemia after treatment. Blood counts are normal, and fewer than 5 percent of bone marrow cells are leukemia cells.
• Recurrent AML occurs when treated AML returns in the blood or bone marrow.

French, American, and British Classification of Acute Myeloid Leukemia

According to the American Cancer Society, the FAB classification placed AML into eight subtypes, M0 through M7. The subtypes are based on the types of leukemia cells found in the body and the cells appear under a microscope. The FAB subtypes of AML are:

• M0 — Undifferentiated acute myeloblastic leukemia
• M1 — Acute myeloblastic leukemia with minimal maturation
• M2 — Acute myeloblastic leukemia with maturation
• M3 — Acute promyelocytic leukemia
• M4 — Acute myelomonocytic leukemia
• M4 eos — Acute myelomonocytic leukemia with eosinophilia (abnormally high blood levels of eosinophils, a type of white blood cell)
• M5 — Acute monocytic leukemia
• M6 — Acute erythroid leukemia
• M7 — Acute megakaryoblastic leukemia

M0 through M5 types of AML develop from immature white blood cells, M6 develops from immature red blood cells, and M7 develops from immature platelet cells.

The FAB classification system can be helpful, but it doesn’t consider other factors that can affect the prognosis (outlook) for AML. Also, because it relies on how blood cells look under a microscope, there’s some subjectivity — diagnoses may vary among pathologists (doctors who study body tissues and fluids to diagnose diseases). For these reasons, the WHO classification (described below) is generally preferred.

World Health Organization Classification of Acute Myeloid Leukemia

The WHO’s updated classification system for AML includes genetic changes that can occur in cancer cells, the types of cells affected, and how quickly the cancer cells grow. The main WHO subtypes of AML are:

• AML with recurrent genetic abnormalities
• AML defined by differentiation
• AML, myelodysplasia-related
• Myeloid sarcoma

Health care providers can identify genetic changes in AML cancer cells to help determine a person’s prognosis. Some genetic changes are linked to a better outlook than others.

Chronic Lymphocytic Leukemia Stages

There are two major staging systems for CLL: Rai and Binet.

Rai Classification of Chronic Lymphocytic Leukemia

Developed in 1975, the Rai staging system for CLL is most commonly used in the United States. The Rai system focuses on the number of lymphocytes in the blood and bone marrow. Having too many of these infection-fighting white blood cells, called lymphocytosis, may be a sign of leukemia.

All Rai stages involve lymphocytosis, defined as an absolute lymphocyte count higher than 5,000 per microliter of blood. The stages differ based on how much lymphoid tissue (such as lymph nodes, spleen, and liver) is swollen, as well as the levels of red blood cells and platelets. A physical exam can detect swelling, and blood tests measure blood cell counts.

Swollen lymph tissues, more lymphocytes, and fewer red blood cells and platelets occur with more severe CLL. The five Rai stages are:

• Stage 0 (low risk) — There’s no swelling of lymph tissues, and other blood cells (red blood cells and platelets) are normal.
• Stage 1 (intermediate risk) — Lymph nodes are swollen, but not the spleen and liver. The counts of red blood cells and platelets are near normal.
• Stage 2 (intermediate risk) — The spleen is swollen, but there may or may not be swelling in the lymph nodes and liver. Red blood cell and platelet counts are near normal.
• Stage 3 (high risk) — The lymph nodes, spleen, and liver may or may not be swollen, but red blood cells are low (anemia). Platelets are near normal.
• Stage 4 (high risk) — The lymph nodes, spleen, and/or liver may be swollen. The red blood cells might be low or near normal, but platelets are low (thrombocytopenia).

In Rai staging, anemia is defined as hemoglobin below 11 grams per deciliter, and thrombocytopenia is classified as a platelet count below 100,000 per microliter. People in the low-risk category have an expected survival of more than 10 years, and those who fall in the high-risk category have an expected survival of less than four years.

Binet Classification of Chronic Lymphocytic Leukemia

Another staging system for CLL is the Binet staging system, which is often used in Europe. This system is based on the number of swollen lymphoid areas, along with the number of red blood cells and platelets in the blood and bone marrow.

• Stage A — Red blood cell and platelet counts are normal, with fewer than three swollen lymphoid areas.
• Stage B — At least three lymphoid areas are swollen, but red blood cell and platelet counts remain normal.
• Stage C — There may be any number of swollen lymphoid areas, but red blood cell or platelet counts are low.

According to the American Cancer Society, Binet stage A corresponds to Rai stages 0, 1, and 2 and is considered low to intermediate risk. Binet stage B matches Rai stages 1 and 2, with an intermediate risk. Binet stage C aligns with Rai stages 3 and 4 and is classified as high risk.

Chronic Myeloid Leukemia Phases

The updated WHO guidelines describe two phases of CML — chronic and acute — to help predict outlook. The phase of CML can change, so be sure to talk with your health care providers about how they’re classifying your condition. CML phases are based on the percentage of blast cells in the blood and bone marrow:

• Chronic phase — Fewer than 10 percent of these cells are blast cells, and symptoms are mild.
• Acute phase — More than 20 percent of these cells are blast cells, and leukemia symptoms are more noticeable.

The acute phase is also called the blastic phase. In a blast crisis, symptoms often include an enlarged spleen, fever, and fatigue.

Staging Challenges

Staging leukemia can be challenging because of the wide range of genetic changes in each type. However, understanding how a specific leukemia behaves is essential for creating an effective treatment plan.

With advances in technology, researchers are gaining more knowledge about leukemia’s stages and phases. This understanding informs new clinical trials to provide more cancer treatment options, which improve cancer care and outlook for people with leukemia.

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