Leukemia is a cancer originating in the blood and bone marrow, the body’s primary sites for blood cell production. The question of whether leukemia has “stages” is complex because it behaves differently from solid tumors. Unlike cancers that form a measurable mass, leukemia cells are already widely distributed throughout the circulatory system. Therefore, the traditional staging systems used for solid tumors do not apply to most forms of leukemia. Instead, doctors rely on alternative classification, risk stratification, and phasing systems to define disease severity and determine the most appropriate treatment plan.
Why Leukemia Is Not Staged Like Solid Tumors
The concept of cancer staging is primarily built around the TNM (Tumor, Node, Metastasis) system. This system evaluates the size of a primary tumor (T), spread to nearby lymph nodes (N), and metastasis to distant organs (M). This framework is not applicable to leukemia because it is a liquid cancer affecting the blood and bone marrow, meaning the abnormal cells are inherently systemic. Leukemia cells do not form a localized mass that can be measured, nor do they need to “metastasize” since they already circulate throughout the body.
The focus shifts away from anatomical spread and toward the biological characteristics of the cancerous cells. Classification depends on the specific type of blood cell affected (myeloid or lymphoid) and the speed of progression (acute or chronic). Assessment of severity relies heavily on laboratory findings, such as cell counts and the presence of specific genetic or chromosomal abnormalities.
Classification Systems for Acute Leukemias
Acute leukemias, such as Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), are characterized by the rapid production of immature white blood cells, known as blasts. These blasts accumulate in the bone marrow and blood, preventing the production of healthy, mature blood cells. Instead of numbered stages, acute leukemias are assigned a “risk group” based on cellular characteristics. Diagnosis is typically made when blast cells make up 20% or more of the cells in the bone marrow or blood.
Modern classification systems, like those from the World Health Organization (WHO), prioritize genetic and molecular markers over older methods based solely on cell appearance. For example, in AML, genetic changes such as the t(8;21) translocation or mutations in the NPM1 gene indicate a favorable risk group. Conversely, complex karyotypes or mutations in genes like TP53 are associated with adverse risk and a less favorable outlook. This genetic-based risk stratification system guides the intensity of treatment required, measuring the disease’s underlying biology rather than its physical location.
Staging Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia (CLL) is the type of leukemia that most closely utilizes traditional staging systems, based on the extent of the disease’s physical presentation. The two most widely used systems are the Rai system, common in the United States, and the Binet system, used in Europe. These systems assess the number of abnormal white blood cells and the degree to which the disease has involved the lymph nodes and organs.
The Rai system divides CLL into five stages (0 through IV), grouped into low, intermediate, and high-risk categories. Stage 0 is characterized only by elevated lymphocytes (lymphocytosis), with no enlarged lymph nodes, spleen, or liver. Stages I and II are intermediate risk, involving enlarged lymph nodes (Stage I) or an enlarged spleen or liver (Stage II). The high-risk stages, III and IV, are defined by the presence of anemia (low red blood cell count) or thrombocytopenia (low platelet count), indicating significant bone marrow failure.
The Binet staging system simplifies this assessment into three categories: A, B, and C. Stage A involves less than three groups of enlarged lymph nodes, with normal red blood cell and platelet counts. Stage B involves the enlargement of three or more lymph node groups, while blood counts remain normal. Stage C, the most advanced category, is defined by the presence of anemia or thrombocytopenia, regardless of the number of enlarged lymph node areas. Both systems predict disease progression and help doctors decide when treatment is necessary.
Phases of Chronic Myeloid Leukemia
Chronic Myeloid Leukemia (CML) is assessed using “phases” rather than stages to describe its progression. CML is defined by the presence of the Philadelphia chromosome, a genetic abnormality that creates the BCR-ABL fusion gene. CML typically progresses through three phases reflecting aggressiveness and responsiveness to treatment.
The first and longest is the Chronic Phase, where patients have a low number of blasts (immature cells), typically less than 10%, in the blood and bone marrow. Symptoms are mild, and the disease usually responds well to targeted drug therapies.
If the disease becomes more aggressive, it enters the Accelerated Phase, marked by 10% to 19% blasts or the development of new chromosomal abnormalities. This phase indicates the disease is progressing faster and is less responsive to standard treatment.
The final, most aggressive state is the Blast Phase, sometimes called a blast crisis, which functions like an acute leukemia. This phase is defined by 20% or more blasts in the blood or bone marrow, often forming clusters outside the bone marrow, requiring intensive chemotherapy.