- 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.
- 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.
- 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.
- 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.
- 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.