Chronic Leukemia

Types of Chronic Leukemia

• 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

• 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

• 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

• 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

• 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.

Living With Chronic Leukemia

Chronic leukemia is usually lived with for years, and the day-to-day work differs by type: monitoring and infection prevention for chronic lymphocytic leukemia, and taking a daily targeted pill reliably for chronic myeloid leukemia. The points below are the ones most often unaddressed between oncology visits.

Watch and wait is treatment, not neglect

Most people with early CLL are monitored rather than treated, because starting therapy before it is needed does not lengthen life. Treatment begins when symptoms appear, when anemia or low platelets develop, when the lymphocyte count is doubling quickly, or when nodes or the spleen become bulky. When it does begin, oral targeted drugs have largely replaced chemotherapy. Blood counts are checked every few months, and our blood work guide explains the numbers.

Infection is the main risk in CLL

CLL weakens antibody production even when the count is stable, so infections are the most common serious complication. Annual influenza, updated COVID-19, pneumococcal, and the recombinant shingles vaccine are given, ideally before treatment starts, and live vaccines are avoided; our adult vaccine checklist covers timing. Recurrent bacterial infections with low antibody levels are treated with replacement immunoglobulin, and a fever during treatment is evaluated the same day; the acquired immune deficiencies page covers the precautions.

Skin cancer and the Florida sun

People with CLL develop skin cancers, particularly squamous cell, several times more often than the general population, and they behave more aggressively, so a full-skin examination every year, daily sunscreen, and prompt attention to any changing spot are routine; our skin cancer screening article explains the exam, and the basal and squamous cell page covers the lesions. Autoimmune destruction of red cells or platelets also occurs in CLL and is treated differently from marrow failure.

CML: the pill only works if it is taken

Tyrosine kinase inhibitors such as imatinib keep CML in remission for as long as they are taken, and missing doses is the most common reason a response is lost. A blood PCR test for BCR-ABL every three months tracks the response, and a rising result prompts a check of adherence before a change of drug. Some of these medications interact with common drugs, including certain antacids and antifungals, so every new prescription is checked. After several years of deep, stable response, a supervised trial off treatment is possible for selected people.

Symptoms that mean a call

Fever, drenching night sweats, rapid weight loss, a new lump, or pain under the left ribs is reported promptly, because it can signal progression or infection. Our hematology team coordinates blood counts, vaccines, and screening between oncology visits. The National Cancer Institute publishes patient guidance on chronic lymphocytic leukemia and chronic myeloid leukemia.

If you have chronic leukemia and have not had a skin examination or a vaccine review in the past year, schedule a visit.