Chronic myeloid leukemia

Disease Description (Causes and Symptoms)

Chronic myeloid leukemia (CML) is a chronic blood cancer in which myeloid-lineage cells proliferate abnormally in the bone marrow. In most cases (approximately 90% or more), the Philadelphia chromosome is formed through a translocation between chromosomes 9 and 22. The BCR-ABL protein (an abnormal tyrosine kinase) produced by the BCR-ABL fusion gene continuously activates cell-proliferation signals, causing proliferation of myeloid progenitor cells and inhibition of apoptosis, which leads to the disease.
Major symptoms: fatigue, loss of appetite and weight loss, sweating (especially night sweats), frequent infections, a tendency to bleed (such as gum bleeding and nosebleeds), abdominal fullness and early satiety (due to splenomegaly), and hepatomegaly. Many patients are asymptomatic in the early stages, and the disease may be discovered incidentally through blood tests. The disease progresses from the chronic phase → accelerated phase → acute phase (blast phase); as it progresses, anemia, bleeding, and the frequency of infections increase, and symptoms caused by tissue infiltration become more severe.

Treatment Methods

• Standard drug treatment (targeted therapy)
  • First-generation tyrosine kinase inhibitor (TKI): imatinib (Gleevec, generally 400 mg/day in the chronic phase; the dose may be increased depending on the case in the accelerated or acute phase). It selectively inhibits the tyrosine kinase of BCR-ABL and has a significant effect on disease control.
  • Second-generation TKIs: nilotinib (Tasigna), dasatinib (Sprycel), bosutinib, etc. — These may be used when there is an inadequate response or resistance to Gleevec, or as first-line treatment. Some studies have shown a faster molecular response when used as first-line treatment.
  • Third-generation TKI: ponatinib (Iclusig) — Effective against certain resistant mutations (such as T315I), but should be used cautiously because of the risk of serious adverse effects, including cardiovascular effects.
• Hematopoietic stem cell transplantation
  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment known to date. Eligibility is determined based on age, disease stage, donor compatibility, and overall condition. In general, transplantation during the chronic phase is associated with lower rates of relapse and mortality.
• Adjunctive and supportive treatment
  • Infection management (prevention and treatment), transfusions, and symptomatic treatment for bleeding and anemia.
• Treatment monitoring and goals
  • Hematologic response (complete hematologic response), cytogenetic response, and molecular response (qPCR-based BCR-ABL level). Treatment goals are generally monitored at 3 months (early molecular response ≤10%), 6 months (≤1%), and 12 months, including MMR (BCR-ABL ≤0.1% IS).
• Treatment discontinuation (Treatment-Free Remission, TFR)
  • If strict criteria (such as sustained deep molecular response) are met, discontinuation of the TKI may be considered under the supervision of the treating physician. However, frequent molecular testing is necessary because there is a risk of relapse.

Precautions (Treatment-Related)

• Each TKI has characteristic adverse effects (edema, muscle cramps, gastrointestinal symptoms, abnormal liver function, decreased platelet and neutrophil counts, QT prolongation, arterial thrombosis, etc.). Use during pregnancy or breastfeeding is contraindicated or carries risks.
• In cases of drug resistance or molecular relapse, appropriate treatment options (changing the drug, adjusting the dose, transplantation, etc.) are determined through mutation testing (BCR-ABL kinase domain mutation).

Checklist Before an Outpatient Visit (Including Example Questions)

Items to Prepare and Check

• A list of all currently used medications and supplements (including doses and times of administration)
• Recent blood test results: CBC (complete blood count), liver and kidney function tests, and electrolytes
• Recent quantitative BCR-ABL test (qPCR) results (if possible, the values based on the IS standard) and records of previous tests
• Results of previous bone marrow tests, chromosome tests, and mutation tests (kinase domain)
• Symptom records: fever or infections, bleeding or bruising, weight changes, abdominal fullness (related to spleen size), shortness of breath, dizziness, etc.
• For women of childbearing age, pregnancy status and contraception plans (TKIs pose a risk to the fetus during pregnancy)
• Lifestyle information: smoking, alcohol consumption, and underlying conditions (hypertension, diabetes, dyslipidemia, and cardiovascular disease)
• Recent vaccination history (especially influenza and pneumococcal vaccines) and immune status

Example Questions to Ask During a Doctor's Visit (For Test and Treatment Preparation)

• What is my recent BCR-ABL level, and what is my current molecular response status (for example, MMR or DMR)?
• What are the major adverse effects of my current medication, and could the symptoms I am experiencing be related to the medication?
• Is a change in medication necessary based on the mutation test results?
• How would treatment discontinuation work (the expected relapse rate and monitoring schedule after discontinuation)?

General Example Questions to Ask the Doctor

• What are the common and serious adverse effects of this medication (the currently prescribed TKI)? How should I respond if they occur?
• How should my current molecular response (BCR-ABL level) and prognosis be interpreted?
• When is hematopoietic stem cell transplantation necessary, and what are its benefits and risks?
• I am planning a pregnancy. How should I prepare? (For both men and women)
• How often should I undergo which tests (blood tests, qPCR, mutation testing, etc.)?

Examples of Disease-Specific Questions

• A specific mutation was found in my BCR-ABL mutation test (for example, T315I). Which medications can be selected? Should transplantation take priority?
• My current BCR-ABL level has not reached the target (for example, ≤10% at 3 months). Is changing the medication or increasing the dose recommended?

Precautions, Complications, and Prognosis

• Complications: As the disease progresses, it may transform into acute leukemia (blast phase), cause serious infections and bleeding, and worsen symptoms due to organ infiltration (such as the liver and spleen). TKI-related complications include hepatotoxicity, bone marrow suppression (anemia, neutropenia, and thrombocytopenia), edema, musculoskeletal pain, skin rash, hyperglycemia and lipid abnormalities (mainly with nilotinib), increased pulmonary arterial pressure (rarely with dasatinib), and vascular events (with an increased risk associated with nilotinib, ponatinib, etc.).
• Prognosis: The introduction of TKIs has greatly improved long-term survival in the chronic phase, and many patients maintain long-term remission or disease control. Patients who achieve an early molecular response have a good prognosis. However, the prognosis is poor in cases of treatment failure or resistance (especially certain mutations) or advanced disease stages, and allogeneic transplantation may be considered.
• Points to note for self-management: Adherence to medication (taking it at the same time every day), regular blood and molecular testing, avoiding contraindicated medications (consult a doctor), prior counseling and adherence to contraception when planning a pregnancy, and prompt medical care if an infection develops.

(Note: Exposure to high doses of radiation is known to be a risk factor. Special screening for the general population is not recommended, and specialist consultation is recommended when abnormal findings such as an elevated white blood cell count are present.)