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 pinpointing effective treatments. For most cancers, the stage depends on the size and location of tumors, and how far the cancer has spread in the body.
Leukemia behaves differently from most cancers. Since leukemia is a blood cancer, it typically does not form solid tumors and has usually spread throughout the body before it is diagnosed. Therefore, the stages of leukemia are characterized differently from other types of cancer. While some types of leukemia are described using different stages, others are characterized as specific subtypes or classifications and are not staged like other types of cancers.
There are many different kinds of leukemia, which are described by how quickly the cancer progresses and the types of cells that are involved. There are subtypes within each group. The four main types of leukemia are:
Leukemia cells are immature white blood cells (also called blast cells) that develop certain genetic mutations. These mutations make the cells grow abnormally quickly. As the leukemia cells expand, they can crowd out other cell types — like red blood cells (RBCs) and platelets. When there are too many leukemia cells and not enough of the other blood cells, the body has a more difficult time fighting infections, transporting oxygen, and clotting properly. This imbalance of blood cell types leads to symptoms of leukemia like weakness, fatigue, swollen lymph nodes, muscle aches, bone and joint pain, shortness of breath, anemia (not enough RBCs), cuts that don’t clot well due to low platelets (thrombocytopenia), and bruising. Occasionally, leukemia cell numbers can grow to such an extent that they can obstruct blood vessels and cause heart attacks, strokes, or vascular problems. Very high numbers of leukemia cells can also produce a fever and cause weight loss.
ALL doesn’t have a standard staging system. Instead, it is classified into different subtypes. A group of French, American, and British (FAB) experts originally created a system for characterizing ALL in the 1970s. This system was based on what leukemia cells looked like under a microscope, and included the subtypes L1, L2, or L3. Newer technology and tests now let doctors classify leukemia cells more accurately. The World Health Organization (WHO) updated the ALL classification system in 2016.
The WHO system is based on which kind of white blood cells are cancerous. B cells and T cells are white blood cells that play important roles in the immune system. B cells (also called B lymphocytes) are responsible for making antibodies to fight infections. T cells (also called T lymphocytes) help protect the body from infection.
WHO classifies ALL as:
Subtypes within these categories depend on specific genetic changes seen in the cells.
The National Cancer Institute explains that AML can be described as untreated, in remission, or recurrent.
According to the American Cancer Society, a group of French, American, and British (FAB) leukemia experts worked together to categorize AML into eight subtypes in the 1970s. The subtypes were labeled M0 through M7. These subtypes are based on the type of leukemia cells present in the body and what they look like under a microscope. These FAB subtypes are:
Subtypes M0 through M5 start from immature white blood cells. M6 starts from immature RBCs, and M7 starts from immature platelet cells.
The FAB classification system can be helpful, but it is only based on how the cells look under a microscope. The FAB system does not consider factors that can affect the outlook for AML.
The World Health Organization (WHO) updated a classification system for AML in 2016. The WHO system is based on genetic changes that can happen in cancer cells, which cells are affected, and how quickly the cancer cells grow. The major WHO subtypes of AML are:
Doctors can detect the genetic changes in the cancer cells of AML to determine a person’s prognosis. Some genetic changes have a better outlook than others.
There are two major staging systems for CLL: Rai and Binet.
The Rai classification system for CLL was developed in 1975 and is most commonly used in the United States. Rai stages are based on the number of lymphocytes, a type of white blood cell in the blood and bone marrow. Lymphocytes include T cells and B cells, which play important roles in fighting off bacteria and viruses. When there are too many lymphocytes, this is indicative of leukemia and is called lymphocytosis.
All of the Rai stages involve lymphocytosis, but the different stages depend on the enlargement of lymph tissues (lymph nodes, spleen, and liver), and the number of red blood cells and platelets. An enlarged spleen, enlarged lymph nodes, or an enlarged liver can be found during a physical exam. Blood cell counts can be determined using a blood test.
Enlarged lymph tissues, more lymphocytes, and fewer red blood cells and platelets occur with more severe CLL. The five Rai stages are:
Another staging system for CLL is the Binet staging system. The Binet staging system is more commonly used in Europe. This system is based on the number of enlarged lymph tissue areas (lymph nodes or liver) and the number of red blood cells and platelets in the blood and bone marrow.
The American Society of Clinical Oncology notes that Binet stage A corresponds to Rai stages 0, 1, and 2, and is low or intermediate risk. Binet stage B corresponds to Rai stages 1 and 2 and is intermediate risk. Binet stage C corresponds to Rai stages 3 and 4 and is high risk.
The American Cancer Society, based on WHO guidelines, describes three phases of CML that can help predict outlook: chronic, accelerated, and blast. CML stages can change, and different doctors might have slightly different definitions. The American Cancer Society suggests talking with your oncologist if you are unsure how they classify CML. CML phases are based on the number of blasts (immature white blood cells) in the blood and bone marrow.
In the chronic phase, leukemia symptoms are mild and fewer than 10 percent of cells in the blood and bone marrow are blast cells.
If one of the following conditions is present, CML is considered to be in the accelerated phase:
In the acute phase, bone marrow or blood cells contain more than 20 percent blast cells, and leukemia symptoms are present. This is also called the blastic phase. When this condition is accompanied by an enlarged spleen, fever, and tiredness, it is called blast crisis.
Staging of leukemia can be difficult due to the variability of this disease. There are many genetic changes or abnormalities within each type of leukemia. However, understanding how a cancer behaves is important to determine an effective treatment plan. As technology advances, researchers can better understand the different stages and phases of leukemia to provide more treatment options and improve the outlook for people with leukemia.