Chronic leukemia is a type of cancer that starts in the blood-forming cells of the bone marrow. In chronic leukemia, the abnormal white blood cells (leukemia cells) are more mature than those in acute leukemia, and they proliferate more slowly. They can still function somewhat normally in the beginning, but over time, they accumulate in the blood, bone marrow, and other organs (like the spleen and liver), crowding out healthy blood cells. This leads to a range of symptoms as the number of healthy red blood cells, white blood cells, and platelets decreases. Chronic leukemias typically progress more slowly than acute leukemias, and individuals may live for many years without significant symptoms or requiring intensive treatment in the early stages.
Types of Chronic Leukemia:
The two main types of chronic leukemia are categorized by the type of white blood cell affected: myeloid or lymphoid.
- Chronic Myeloid Leukemia (CML):
- Affects myeloid cells (which develop into red blood cells, platelets, and most types of white blood cells).
- Characterized by the presence of the Philadelphia chromosome, a genetic abnormality where parts of chromosomes 9 and 22 swap places, creating a fusion gene called BCR-ABL. This gene produces an abnormal protein (tyrosine kinase) that causes myeloid cells to grow out of control.
- Typically progresses through three phases: chronic, accelerated, and blastic.
- Chronic Lymphocytic Leukemia (CLL):
- Affects lymphoid cells (lymphocytes), specifically B lymphocytes.
- It is the most common type of leukemia in adults.
- CLL cells accumulate slowly in the blood, bone marrow, lymph nodes, and spleen.
- Often progresses very slowly, and many people live for years without needing treatment.
- Other Rare Chronic Leukemias:
- Hairy Cell Leukemia: A rare, slow-growing cancer of B lymphocytes, characterized by abnormal “hairy” cells.
- Chronic Myelomonocytic Leukemia (CMML): A type that has features of both myelodysplastic syndromes and myeloproliferative neoplasms.
Causes:
The exact causes of most chronic leukemias are unknown, but they are believed to result from acquired (not inherited) genetic mutations in bone marrow stem cells. These mutations lead to the uncontrolled growth of abnormal white blood cells.
- Acquired Genetic Mutations:
- For CML, the primary cause is the Philadelphia chromosome (BCR-ABL gene), which is an acquired mutation, not usually inherited.
- For CLL, while a specific single cause isn’t identified, it involves genetic changes (mutations or deletions) in B lymphocytes that lead to their uncontrolled proliferation and survival. These mutations are also acquired, not typically inherited.
- Risk Factors for CML:
- Radiation Exposure: High-dose radiation (e.g., from atomic bomb survivors, certain radiation therapy). This is the only clearly established environmental risk factor.
- Age: Risk increases with age.
- Risk Factors for CLL:
- Age: Most common in older adults (average age at diagnosis is 70).
- Gender: More common in men than women.
- Family History: Having a close relative with CLL or other blood cancers slightly increases risk.
- Race/Ethnicity: More common in North America and Europe.
- Exposure to Certain Chemicals: Some studies suggest a possible link to certain pesticides or herbicides, but evidence is not conclusive.
- No clear link to: Smoking, specific diets, or infections.
Symptoms:
Many individuals with chronic leukemia, especially in the early stages, have no symptoms and are diagnosed incidentally during routine blood tests. When symptoms do appear, they are often non-specific and related to the accumulation of abnormal cells or the deficiency of healthy blood cells.
- Early or Non-Specific Symptoms:
- Fatigue: Persistent tiredness.
- Weakness.
- Weight Loss: Unexplained.
- Loss of Appetite.
- Low-Grade Fever.
- Night Sweats.
- Feeling Full After Eating Small Amounts: Due to an enlarged spleen.
- Easy Bruising or Bleeding: Due to low platelet counts (thrombocytopenia).
- Frequent Infections: Due to a reduction in functional white blood cells.
- Specific Symptoms Related to Cell Accumulation:
- Enlarged Lymph Nodes: Painless swelling in the neck, armpits, or groin (more common in CLL).
- Enlarged Spleen (Splenomegaly): Can cause a feeling of fullness, discomfort, or pain under the left ribs (common in both CML and CLL).
- Enlarged Liver (Hepatomegaly): Less common, but can occur.
- Symptoms of Progression (especially in CML or advanced CLL):
- More severe fatigue, weight loss, fever.
- Bone or joint pain.
- Worsening anemia.
- More frequent or severe infections.
- Increased bleeding.
- In CML, progression to the accelerated or blastic phase can cause symptoms similar to acute leukemia.
Diagnosis:
Diagnosis of chronic leukemia typically begins with routine blood tests, followed by specialized tests to confirm the diagnosis, classify the type of leukemia, and assess its stage.
- Complete Blood Count (CBC) with Differential:
- Often the first indication. Shows abnormally high white blood cell counts (leukocytosis), particularly mature lymphocytes in CLL or granulocytes in CML.
- May also show anemia (low red blood cells) and/or thrombocytopenia (low platelets).
- Peripheral Blood Smear:
- A microscopic examination of a blood sample to visualize the abnormal white blood cells and assess their morphology.
- Helps differentiate types of leukemia.
- Bone Marrow Aspiration and Biopsy:
- Crucial for confirming the diagnosis, assessing the percentage of leukemia cells in the marrow, and evaluating for other bone marrow changes.
- Cytogenetic Analysis / FISH (Fluorescence In Situ Hybridization):
- For CML: To detect the Philadelphia chromosome and BCR-ABL fusion gene.
- For CLL: To identify specific chromosomal abnormalities (e.g., deletions in 13q, 11q, 17p; trisomy 12), which can influence prognosis and treatment.
- Molecular Genetic Tests (PCR – Polymerase Chain Reaction):
- For CML: To detect and quantify the BCR-ABL gene transcripts, useful for diagnosis and monitoring treatment response.
- For CLL: To detect mutations in certain genes (e.g., IGHV, TP53) that provide prognostic information.
- Flow Cytometry:
- Analyzes cell markers on the surface of leukemia cells to accurately classify the type of chronic leukemia (e.g., confirming CLL as a B-cell leukemia).
- Imaging Tests (less common for diagnosis, more for staging/complications):
- CT Scan (Computed Tomography): To check for enlarged lymph nodes, spleen, or liver.
- PET Scan (Positron Emission Tomography): Less common, but may be used to identify areas of disease activity.
Treatment:
Treatment for chronic leukemia depends heavily on the specific type, stage, genetic factors, and the patient’s symptoms and overall health. The goal is to control the disease, manage symptoms, and improve quality of life. Some chronic leukemias may not require immediate treatment.
- Watchful Waiting (Active Surveillance):
- Often the initial approach for early-stage, asymptomatic CLL. The patient is regularly monitored, and treatment is started only if symptoms develop or the disease shows signs of progression.
- For Chronic Myeloid Leukemia (CML):
- Tyrosine Kinase Inhibitors (TKIs): (e.g., imatinib – Gleevec, nilotinib – Tasigna, dasatinib – Sprycel, bosutinib – Bosulif, ponatinib – Iclusig). These are highly effective targeted therapies that specifically block the activity of the BCR-ABL protein, transforming CML management. They are the first-line treatment.
- Chemotherapy: Less commonly used now, but may be used in advanced phases or if TKIs are not effective.
- Stem Cell Transplantation (Bone Marrow Transplant): Potentially curative, but often reserved for patients who do not respond to TKIs or who are in advanced stages, due to significant risks.
- For Chronic Lymphocytic Leukemia (CLL):
- Chemotherapy: (e.g., fludarabine, cyclophosphamide). Older regimens, often used in combination.
- Targeted Therapies:
- Bruton’s Tyrosine Kinase (BTK) Inhibitors: (e.g., ibrutinib, acalabrutinib, zanubrutinib) Highly effective oral medications.
- Bcl-2 Inhibitors: (e.g., venetoclax) Target a protein that helps cancer cells survive.
- Monoclonal Antibodies: (e.g., rituximab, obinutuzumab) Target specific proteins on CLL cells, often used in combination with chemotherapy or targeted therapies.
- Stem Cell Transplantation: Rarely used, typically for very young patients with high-risk CLL who fail other treatments.
- Supportive Care:
- Blood Transfusions: For anemia.
- Platelet Transfusions: For low platelet count and bleeding.
- Growth Factors: To stimulate white blood cell production if needed.
- Antibiotics/Antivirals/Antifungals: To treat or prevent infections.
- Radiation Therapy: To shrink enlarged lymph nodes or spleen, or for localized pain.
Chronic leukemia management is highly individualized and requires ongoing care by a hematologist-oncologist, who will monitor the disease and adjust treatment as needed. Advances in targeted therapies have significantly improved the prognosis for many patients.
