Staging is a method used to describe or classify cancer based on how much of it is present in the body. For cancers that develop solid tumors, stages are assigned numbers depending on the size of the tumor and whether the cancer has spread to lymph nodes or other areas of the body. However, leukemia—a type of blood cancer—does not typically follow the same staging system.
Unlike solid tumors, leukemia does not form masses that can be measured or localized. Instead, leukemia is classified using other methods that focus on specific factors like white blood cell counts, genetic mutations, and overall disease progression. While chronic lymphocytic leukemia (CLL) has a staging system (the Rai, Binet, and CLL-IPI systems), most types of leukemia are categorized based on their type, severity, and how they affect the body.
The term "stages of leukemia" is commonly searched and often misunderstood. Rather than a strict staging system, tools and classifications are in place to guide diagnosis and determine treatment. Recognizing the symptoms and understanding these classifications can help individuals and families navigate the diagnosis and treatment process effectively.
Stages of Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is one of the few leukemias that use a defined staging system, called the Rai system.
The Rai system helps determine how far the leukemia has progressed, guiding treatment decisions and helping to predict the leukemia survival rate (Tausch et al. 2020)(Mukkamalla et al. 2023). The Rai system categorizes CLL into five stages:
- Stage 0: This early stage of leukemia is marked by high white blood cell counts without significant symptoms. Patients may not need treatment right away, as the disease progresses slowly.
- Stage I: Involves swollen lymph nodes but no signs of low red blood cell count (anemia) or low platelet count (thrombocytopenia).
- Stage II: This stage is characterized by an enlarged spleen or liver in addition to swollen lymph nodes.
- Stage III: Indicates anemia due to leukemia cells crowding the bone marrow.
- Stage IV: The last stages of leukemia in CLL involve low platelet counts, which increase the risk of bleeding.
The Binet system is a simple way to classify CLL into three stages based on blood test results and the number of swollen lymph nodes or other lymphatic areas (Halek 2019).
- Stage A: No anemia (low red blood cells) or low platelets. Fewer than three enlarged lymph node areas.
- Stage B: No anemia or low platelets, but three or more enlarged lymph node areas.
- Stage C: Anemia or low platelets, regardless of the number of enlarged lymph node areas.
The CLL-IPI system uses key factors to predict how aggressive CLL is and guide treatment decisions (Halek 2019). These factors include:
- Genetic changes: Mutations in the TP53 gene or unmutated IGHV gene.
- Blood marker: High beta-2 microglobulin levels (a protein linked to disease activity).
- Disease stage: Advanced stages (Binet B-C or Rai I-V).
- Age: Over 65 years.
Patients are grouped into four risk categories based on a points system:
- Low Risk (0-1 points): No treatment needed.
- Intermediate Risk (2-3 points): Only treat if symptoms are severe.
- High Risk (4-6 points): Treatment is usually recommended unless no symptoms.
- Very High Risk (7-10 points): Consider newer treatments or clinical trials rather than traditional chemotherapy.
Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia (ALL) is a fast-developing form of leukemia that requires immediate treatment. ALL does not have clearly defined stages, such as early or late stages. In this context, the first stage of leukemia in ALL is not defined the same way as in other cancers, where staging is more structured.
Instead, it is classified by factors like the type of affected lymphocyte (B-cell or T-cell) and specific genetic mutations. Diagnosis focuses on the spread of leukemia cells in the blood, bone marrow, and potentially other organs, such as the central nervous system (CNS). Doctors use this information to guide treatment and determine prognosis. ALL is broadly described based on treatment phases: untreated, in remission, or relapsed (Jabbour et al. 2023) (Arber et al. 2016).
- Untreated: This phase refers to newly diagnosed acute lymphoblastic leukemia (ALL) where the patient has not yet started treatment. Leukemia cells are present in the blood or bone marrow, and symptoms are evident.
- In Remission: In this phase, treatment has reduced the number of leukemia cells to undetectable levels, and the patient shows no symptoms. Normal blood cell counts are restored, but the disease may still be present in small amounts.
- Relapsed: This occurs when leukemia returns after a period of remission, meaning leukemia cells reappear in the blood, bone marrow, or other parts of the body.
Treatment typically begins right after diagnosis and may involve chemotherapy, targeted therapy, or stem cell transplants to achieve remission.
Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) also doesn't follow a traditional stage-based classification but instead is categorized according to its progression and specific genetic characteristics. AML originates from the myeloid line of cells in the bone marrow and spreads quickly without early treatment. Doctors classify AML based on factors like the type of myeloid cell affected, genetic mutations present in the leukemia cells, and whether it is a new case or a relapse.
The World Health Organization (WHO) system is the main method used to group AML into subtypes (Arber et al. 2022). These subtypes are based on:
- Genetic changes: Specific gene or chromosome abnormalities in leukemia cells (myeloblasts).
- Blast percentage: The amount of leukemia cells in the bone marrow or blood.
This classification helps doctors understand the type of AML and choose the best treatment plan.
AML treatment focuses on inducing remission and, depending on risk factors, may involve chemotherapy and possibly stem cell transplantation. With an aggressive treatment plan, patients can achieve remission.
Phases of Chronic Myeloid Leukemia (CML)
Chronic myeloid leukemia (CML) progresses through three phases rather than stages (Pfirrmann et al. 2020)(Shah et al. 2024):
- Chronic Phase: This beginning stage of leukemia often presents with few symptoms, and many patients may not feel sick. Blood tests show elevated white blood cell counts. Treatment with tyrosine kinase inhibitors (TKIs) typically keeps the disease under control for long periods.
- Accelerated Phase: In this phase, the disease progresses more rapidly, and blood counts become more difficult to control.
- Blast Crisis Phase: This phase is similar to acute leukemia and represents the final stages of leukemia, where there is an overwhelming presence of immature leukemia cells, or blasts. This phase requires aggressive treatment.
Hairy Cell Leukemia (HCL)
Hairy cell leukemia (HCL) is a rare type of chronic leukemia that does not have distinct stages. Instead, HCL is described by how far it has progressed and how significantly it affects blood counts. Hairy cell leukemia typically causes a decrease in healthy blood cells, leading to symptoms like fatigue, frequent infections, and anemia.
HCL is often classified based on the response to treatment, with doctors describing it as either active or in remission. Treatment often involves chemotherapy or targeted therapy, and many individuals achieve long-term remission, though follow-up care is important for managing any signs of relapse (Tiacci et al. 2017)(Naing, Acharya, and Kumar 2023).
Categories of Chronic Myelomonocytic Leukemia (CMML)
Chronic myelomonocytic leukemia (CMML) is another rare blood cancer that combines features of both leukemia and myelodysplastic syndromes. CMML is classified into two categories (Onida 2017)(Harrington et al. 2016):
- CMML-0: Very low levels of immature cells (blasts) are present in the bone marrow and blood.
- CMML-1: Few immature cells are present in the bone marrow and blood.
- CMML-2: A higher number of blasts is present, indicating more advanced disease and a higher risk of progression to acute myeloid leukemia.
Juvenile Myelomonocytic Leukemia (JMML)
Juvenile myelomonocytic leukemia (JMML) is a rare childhood leukemia that does not have traditional stages. Instead, JMML is categorized based on its severity and the presence of specific genetic mutations that impact how the disease progresses. Treatment for JMML often involves chemotherapy, and a stem cell transplant is the most common approach for achieving long-term remission (Niemeyer and Flotho 2019)(National Cancer Institute (US) 2024).
Large Granular Lymphocytic (LGL) Leukemia
Large granular lymphocytic (LGL) leukemia is a rare, slow-progressing chronic leukemia characterized by the abnormal growth of large granular lymphocytes. LGL lacks a specific staging system due to its gradual progression; instead, the disease is “staged” based on the number of abnormal lymphocytes, the presence of symptoms, and its impact on organ function, particularly the bone marrow, spleen, and liver. It can be indolent, meaning it progresses slowly with minimal symptoms, or aggressive, which requires prompt treatment (The Leukemia & Lymphoma Society 2024)(Magnano, Rivero, and Matutes 2022).
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon form of leukemia with aggressive characteristics. BPDCN is not staged like many other cancers because of its rarity but is instead described by the extent of the disease upon diagnosis (Sangle, Chin-Yee, and Lam 2015)(Jain and Sweet 2023):
- Localized BPDCN: Cancer is limited to the skin.
- Regional BPDCN: Cancer has spread to nearby lymph nodes.
- Distant BPCDN: Cancer has spread to distant areas like the bone marrow, central nervous system, or other organs.
Treatment often requires intensive chemotherapy followed by stem cell transplantation due to the aggressive nature of the disease.
B-cell Prolymphocytic Leukemia (B-PLL)
B-cell prolymphocytic leukemia (B-PLL) is an aggressive type of leukemia with no defined stages. It is characterized by a high number of prolymphocytes in the blood. Treatment usually begins soon after diagnosis and involves chemotherapy and possibly targeted therapies to achieve remission (The Leukemia & Lymphoma Society 2024)(Menakuru, Roepke, and Siddiqui 2023).
T-cell Prolymphocytic Leukemia (T-PLL)
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive form of leukemia. Like B-PLL, T-PLL does not have defined stages but is categorized based on symptoms and blood cell counts. Patients often present with an enlarged liver or spleen and require prompt treatment. Therapies may include chemotherapy, targeted treatments, and monoclonal antibodies to achieve disease control (The Leukemia & Lymphoma Society 2024)(Gutierrez et al. 2023).
Conclusion
The stages of leukemia vary significantly depending on the type of leukemia involved. Unlike many other cancers, leukemia doesn't typically have defined stages based on tumor size or spread but instead focuses on factors like blood cell counts, symptoms, and genetic mutations. Understanding leukemia and its classification or staging is crucial for determining the best treatment approach and managing expectations for the disease's progression.
If you or someone you care about is navigating leukemia, it's important to remember that there are numerous treatment options and support systems in place, including many resources from The Leukemia & Lymphoma Society (LLS). We are here to offer information, resources, and support every step of the way. Remember, you're not alone—there is hope, and together, we can face leukemia with strength and resilience.
About the author: Dr. Ali is a medical journalist and copywriter.
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