Leukemia stages

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science.

This page was updated on May 26, 2022.

Most cancers are staged based on the size and spread of tumors. However, because leukemia already occurs in the developing blood cells in the bone marrow, leukemia staging is a little bit different. The stages of leukemia are often characterized by blood cell counts and the accumulation of leukemia cells in other organs, like the liver or spleen, with each subtype staged using a system designed specifically for leukemia. 

Making an educated treatment decision begins with the stage, or progression, of the disease. The stage of leukemia is one of the most important factors in evaluating treatment options. Factors affecting leukemia staging and prognosis include:

  • White blood cell or platelet count
  • Age (advanced age may negatively affect prognosis)
  • History of prior blood disorders
  • Chromosome mutations or abnormalities
  • Bone damage
  • Enlarged liver or spleen

Acute lymphocytic leukemia (ALL) stages

A numbered staging system is used to describe most types of cancer and their spread throughout the body. Typically, the size of the tumor and the spread of the cancer are evaluated and a stage is assigned. For acute lymphocytic leukemia (ALL), staging does not occur in this way because the disease originates in the bone marrow and usually does not form tumor masses. Because ALL will likely spread to other organs before it is detected, the staging method would take into account factors other than the spread to differentiate the stages.

Rather than using traditional staging methods, physicians often factor in the subtype of ALL and the patient's age. This usually involves cytologic tests, flow cytometry and other lab tests to identify the subtype of ALL.

B-cell ALL staging

B lymphocytes, or B cells, are produced in the bone marrow. They also mature there. B cells play a large role in humoral immune response and serve the principal functions of making antibodies against antigens and developing into memory B cells after they have been activated by antigen interaction.

  • Early pre-B ALL: Approximately 10 percent of ALL cases
  • Common ALL: Approximately 50 percent of cases
  • Pre-B ALL: Approximately 10 percent of cases
  • Mature B-cell ALL: Approximately 4 percent of cases

T-cell ALL staging

T lymphocytes, or T cells, leave the bone marrow before maturation and move to the thymus, where they mature. T cells play a central role in cell-mediated immunity. There are several different subsets of T cells that have distinct functions. The different subsets of T cells include Helper, Cytotoxic, Memory, Regulatory, Natural killer and Gamma Delta T cells.

  • Pre-T ALL: Approximately 5 to 10 percent of cases
  • Mature T-cell ALL: Approximately 15 to 20 percent of cases

Acute myeloid leukemia (AML) stages

Because acute myeloid leukemia (AML) starts in the bone marrow and is usually not detected until it has spread to other organs, traditional cancer staging is not needed. Rather than using the common TNM method for evaluating the cancer, the subtype of AML is classified using a cytologic (cellular) system. Physicians are better able to predict how the cancer will respond to treatment based on the cellular classification and, in turn, more accurately assess the prognosis.

AML subtypes and staging

Using a system known as French-American-British (FAB) classification, AML is classified in eight subtypes, M0 through M7, based on:

  • The number of healthy blood cells
  • The size and number of leukemia cells
  • The changes that appear in the chromosomes of the leukemia cells
  • Any other genetic abnormalities that have occurred

The eight AML stages are classified as follows:

  • Undifferentiated AML - M0: In this stage of acute myelogenous leukemia, the bone marrow cells show no significant signs of differentiation.
  • Myeloblastic leukemia - M1: Bone marrow cells show some signs of granulocytic differentiation with or without minimal cell maturation.
  • Myeloblastic leukemia - M2: Maturation of the bone marrow cells is beyond the promyelocyte (early granulocyte) stage. Varying amounts of granulocyte maturation may be observed.
  • Promyelocytic leukemia - M3: Most of the abnormal cells are early granulocytes, between myeloblasts and myelocytes in their stage of development. The cells contain many small particles and have nucleuses of varying size and shape.
  • Myelomonocytic leukemia - M4: In this stage of acute myelogenous leukemia, the bone marrow and circulating blood have variable amounts of monocytes and differentiated granulocytes in them. The percentage of monocytes and promonocytes in the bone marrow is greater than 20 percent. There may also be an increased number of granular leukocytes called eosinophils, a type of granulocyte that often has a two-lobed nucleus.
  • Monocytic leukemia - M5: This subset is further divided into two different categories. The first is characterized by poorly differentiated monoblasts with lacy-appearing genetic material. The second subset is characterized by a large number of monoblasts, promonocytes and monocytes. The proportion of monocytes in the bloodstream may be higher than that in the bone marrow.
  • Erythroleukemia - M6: This form of leukemia is characterized by abnormal red blood cell-forming cells, which make up over half of the nucleated cells in the bone marrow.
  • Megakaryoblastic leukemia - M7: The blast cells in this form of leukemia look like immature megakaryocytes (giant cells of the bone marrow) or lymphoblasts (lymphocyte-forming cells). M7 leukemia may be distinguished by extensive fibrous tissue deposits (fibrosis) in the bone marrow.

Chronic lymphocytic leukemia (CLL) stages

Due to the way this disease develops and spreads, chronic lymphocytic leukemia (CLL) staging is different from staging for the kind of cancers that form tumors. Instead of rating the size and extent of tumors, the Rai staging system is based on blood cell counts. The Binet system (more commonly used in Europe than in the United States) summarizes the spread of the cancer throughout the lymph nodes in three stages simply labeled A, B and C. By identifying your stage of chronic lymphocytic leukemia, your team can choose when to begin treatment and determine which CLL treatments may be most effective for you.

Rai staging system for CLL

Chronic lymphocytic leukemia stages in the Rai system are defined by three main factors: the number of the lymphocytes in the blood; whether the lymph nodes, spleen or liver are enlarged; and whether the blood disorders anemia (too few red blood cells) or thrombocytopenia (too few platelets) have developed.

In general, CLL begins as a condition called lymphocytosis, which is having too many lymphocytes. A count of over 10,000 lymphocytes per sample is considered too high and is the benchmark for stage 0. The five stages are labeled 0-4:

  • Rai stage 0 CLL: The levels of the lymphocytes are too high, usually more than 10,000 in one sample. No other symptoms have developed at this point, and other blood cell counts are normal.
  • Rai stage 1 CLL: In addition to the high levels of lymphocytes (lymphocytosis), the lymph nodes are swollen. The levels of red blood cells and platelets are still normal.
  • Rai stage 2 CLL: The number of lymphocytes remains high, and now the liver or spleen might be larger than normal.
  • Rai stage 3 CLL: The excess amount of lymphocytes begins to crowd out the red blood cells, resulting in anemia. The lymph nodes may be swollen, and the liver or spleen may be larger than normal.
  • Rai stage 4 CLL: The levels of red blood cells and platelets drop below normal, causing anemia and thrombocytopenia. The lymph nodes may be swollen, and the liver or spleen may be larger than normal.

The Rai system of chronic lymphocytic leukemia staging is sometimes simplified into low (stage 0), medium (stage 1 and 2) and high (stage 3 and 4) risk categories. Doctors may use this classification to help determine when to begin treatment.

Binet staging system for leukemia

Like the Rai system, advanced stages of chronic lymphocytic leukemia are characterized by the presence of blood disorders resulting from too few red blood cells and platelets. However, instead of relying on the counts from a leukemia blood test, the Binet system evaluates how many areas of lymphoid tissue are affected. (Note: The Binet stages are commonly referred to by clinical stage.)

  • Clinical stage A: Lymph nodes may be swollen, but the cancer is limited to fewer than three areas.
  • Clinical stage B: More than three areas of lymphoid tissues are swollen.
  • Clinical stage C: Either one or both of the blood disorders anemia and thrombocytopenia have developed.

Chronic myeloid leukemia (CML) stages

In order to stage chronic myeloid leukemia (CML), your doctor will examine blood and bone marrow tests to determine the number of diseased cells. There are three stages of CML are:

  • Chronic phase CML: This is the earliest phase of CML. The majority of CML patients are diagnosed during this phase as a result of mild symptoms, particularly fatigue.
  • Accelerated phase CML: If CML has not responded to treatment well during the chronic phase, it becomes more aggressive, which can lead to the accelerated phase. At this point, symptoms may become more noticeable.
  • Blastic phase CML: This is the most aggressive stage of chronic myeloid leukemia. Blastic refers to having more than 20 percent myeloblasts or lymphoblasts. Symptoms are similar to those of acute myeloid leukemia.

Next topic: How is leukemia diagnosed?

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