Chronic lymphocytic leukemia

Chronic Lymphocytic Leukemia (CLL)

1) Disease Description (Causes and Symptoms)

• Summary of definition: A chronic, progressive blood cancer based on mature lymphocytes (mostly B cells), in which lymphocytes accumulate in the peripheral blood, bone marrow, lymph nodes, and spleen.

• Causes: The exact cause is unknown. A family history (CLL or other lymphoproliferative disorders in a first-degree relative) is known to be a risk factor, and genetic predisposition (specific chromosomal abnormalities and gene mutations) affects the disease course. No clear association with the environment, occupation, viruses, or radiation has been established.

• Pathophysiology: Abnormal clonal lymphocytes slowly proliferate and accumulate, suppressing normal blood-cell production (anemia and thrombocytopenia) and causing immune dysfunction (hypogammaglobulinemia, autoimmune hemolysis, etc.). Some genetic abnormalities (del(17p), TP53 mutations, etc.) are associated with a poor prognosis and treatment resistance.

• Main symptoms:

  • Asymptomatic in many patients (incidentally discovered during a health examination)
  • Enlarged lymph nodes (especially in the cervical and supraclavicular regions), enlarged spleen and liver
  • B symptoms: weight loss, fever, night sweats, easy fatigue
  • Anemia (malaise and pallor), bleeding tendency (thrombocytopenia), recurrent infections (reduced resistance)
  • Rarely, involvement of the skin or central nervous system (especially in the T-cell type)

• Prevalence/Epidemiology: Occurs mainly in men over 50. The annual incidence is approximately 1–3 per 100,000 people (varying by region). It is the most common adult leukemia in the United States but is relatively rare in some countries (e.g., Korea).

2) Treatment Methods (Standard Treatment·Medications·Procedures·Lifestyle Management·Precautions)

• Basic principles: In patients with early-stage, asymptomatic, low-risk disease, observation (“watch and wait”) is performed instead of active treatment. Treatment initiation is determined based on symptoms (anemia, thrombocytopenia, enlarging lymph nodes, splenomegaly, persistent weight loss, fever, fatigue, etc.) or hematologic criteria.

• Drug treatment (recent standard)

  • Targeted therapies
    • BTK inhibitors: ibrutinib, acalabrutinib, zanubrutinib — widely used in first-line and relapsed treatment.
    • BCL-2 inhibitor: venetoclax — mainly combined with an anti-CD20 antibody (e.g., obinutuzumab) to induce deep remission. Due to the risk of TLS (tumor lysis syndrome), gradual dose escalation (ramp-up) and monitoring are necessary.
  • Anti-CD20 antibodies: rituximab, obinutuzumab — combined with targeted agents or chemotherapy.
  • Chemoimmunotherapy: FCR (fludarabine + cytarabine? — in fact, FCR is fludarabine + cyclophosphamide + rituximab), bendamustine + rituximab, etc. — considered in younger, physically fit patients (long-term remission may be possible, especially in those who are IGHV mutation-positive). In patients with del(17p)/TP53 mutations, the efficacy of chemotherapy is limited.

• Transplantation

  • Allogeneic hematopoietic stem cell transplantation (allo-SCT): Considered in young patients with high-risk, relapsed, or treatment-resistant disease. Its use is limited because many patients are older.

• Local treatment

  • Radiation: May be used to relieve symptoms caused by localized lymph nodes or the spleen.
  • Splenectomy: Rarely considered when symptoms are caused by massive splenomegaly.

• Supportive care

  • Antibiotics and antiviral agents: Considered for use during infections or prophylactically (depending on treatment status and severity).
  • Intravenous immunoglobulin (IVIG): Prophylactic administration may be considered in patients with recurrent bacterial infections and hypogammaglobulinemia (especially when IgG is decreased).
  • Transfusions (red blood cells and platelets)
  • Apheresis (removal of excess lymphocytes): Intended for temporary relief of symptoms caused by acute hyperlymphocytosis.

• Points of caution during treatment·Complication management

  • Treatment selection is individualized according to the patient’s age, comorbidities, genetic factors (e.g., del17p/TP53), IGHV mutation status, and preferences.
  • BTK inhibitors: Increased risk of bleeding (caution when combined with anticoagulants/antiplatelet agents), possible adverse effects such as atrial fibrillation and hypertension, and the need to check for drug interactions (CYP3A).
  • Venetoclax: Risk of tumor lysis syndrome (TLS) — hospitalization and blood-test monitoring may be necessary.
  • Be alert to infections caused by immunosuppression (consider vaccination and early antibiotic or antiviral treatment). Live vaccines are prohibited (especially during immunosuppression).

• Prognosis: Varies greatly according to stage and genetic abnormalities. Even when remission is achieved, cure is often difficult. (Statistics provided: if untreated, overall survival is 60–80% at 5 years, 20–30% at 10 years, and 10% at 20 years — varying by stage.)

3) Checkpoints Before an Outpatient Visit (Items to Bring·Test Records·Symptom Records, etc.)

• Items to bring (recommended)
  • List of currently used medications, supplements, and anticoagulants (including dosage and administration times)
  • Copies of previous blood tests (recent CBC), bone marrow test and immunophenotyping (flow cytometry), FISH/chromosome and genetic test results (e.g., del(17p), TP53, and IGHV status)
  • Records of previous chemotherapy, hospitalizations, transfusions, and transplantation
  • Vaccination history (especially pneumococcal, influenza, shingles, etc.)
  • Records of recent changes in weight, fever, night sweats, infections (frequency and type), bleeding, bruising, and fatigue
• Information the doctor will check during the visit
  • When symptoms began and how quickly they progressed (presence or absence of B symptoms)
  • Frequency and severity of infections or bleeding
  • Comorbidities (cardiovascular disease, liver and kidney function, diabetes, etc.)
  • Drug allergies and history of previous adverse effects

Example list of questions (items to write down for yourself before the outpatient visit)

• Have you had a fever or recurrent infections during the past 6 months? What about symptoms of anemia or bleeding?
• What medications do you normally take (especially anticoagulants, antiplatelet agents, and heart medications)?
• What chemotherapy drugs have you received previously (names, timing, and response)?

4) Examples of General Questions to Ask the Doctor

• What does my current disease stage mean, and what is the expected course (prognosis)?
• Do I need treatment right now, or is it acceptable to continue observation (sequelae)?
• What treatment do you recommend first in my case, and what are its advantages, disadvantages, and side effects?
• Between targeted therapy (BTK inhibitors, venetoclax, etc.) and chemotherapy, which option is more suitable for me?
• What measures should I take for vaccination and infection prevention?
• Are there any medications I should avoid during treatment (drug interactions), lifestyle restrictions (alcohol and exercise), or dietary restrictions?

5) Examples of Disease-Specific Questions

• My genetic test results show del(17p) or a TP53 mutation. How does this affect treatment selection and prognosis?
• I am currently taking antihypertensive/anticoagulant medication (or have a history of atrial fibrillation). Is it safe to use a BTK inhibitor (e.g., ibrutinib)? Should it be replaced with another medication? -(Optional) If venetoclax treatment is being considered, what is the hospitalization and testing plan to reduce the risk of tumor lysis syndrome?

Note: When consulting with your doctor, presenting your test results (especially blood counts, immunophenotyping, and FISH/genetic results) can help establish a more accurate treatment plan.

(Reference: The above information is general information organized by supplementing the latest standard treatments and precautions based on the provided clinical summary. Please discuss individual treatment decisions with your treating specialist.)