Chronic Myeloid Leukemia Overview
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Questions and Answers

Which mutation is known as the 'gatekeeper' mutation that causes resistance to all currently available TKIs except ponatinib and asciminib?

  • T315I (correct)
  • IKZF1
  • RUNX1
  • ASXL1

    • What are the two phases defined for chronic myeloid leukemia (CML) as recommended by WHO?

  • CML-CP and CML-BP (correct)
  • CML-LP and CML-CP
  • CML-CP and CML-AP
  • CML-AP and CML-BP

    • Patients with which somatic variants may not benefit from TKIs or combination therapies and should be treated with allo-HSCT?

  • ASXL1 mutations (correct)
  • IKZF1 mutations
  • T315I mutations
  • RUNX1 mutations

    • What is the median survival for CML-AP that evolves from CML-CP?

    <p>Less than 3 years</p> Signup and view all the answers

    Which gene is NOT mentioned as one of the most frequently mutated in advanced-stage CML?

    <p>BCR-ABL</p> Signup and view all the answers

    What is the primary genetic change associated with chronic myeloid leukemia (CML)?

    <p>Translocation of ABL1 and BCR genes</p> Signup and view all the answers

    What percentage of newly diagnosed leukemia cases in adults does CML account for?

    <p>15%</p> Signup and view all the answers

    What is a common initial manifestation of chronic phase (CML-CP)?

    <p>Fatigue and weight loss</p> Signup and view all the answers

    Which of the following statements about CML is false?

    <p>Patients are often symptomatic at diagnosis.</p> Signup and view all the answers

    What role does the BCR::ABL1 oncoprotein play in CML?

    <p>It promotes growth and survival of CML cells.</p> Signup and view all the answers

    Which phase of CML is characterized by the highest number of symptomatic patients?

    <p>Blastic Phase</p> Signup and view all the answers

    Which of the following treatment approaches is used to manage resistance to TKIs in CML?

    <p>Switching to alternative TKIs</p> Signup and view all the answers

    What causes the increased proliferation of CML cells?

    <p>Cytokine independent cell cycle</p> Signup and view all the answers

    What percentage of patients typically have the Ph chromosome?

    <p>100%</p> Signup and view all the answers

    Which is a common additional chromosomal abnormality seen in Ph-positive cells?

    <p>Iso(17)</p> Signup and view all the answers

    What is the typical translocation associated with Ph-positive CML?

    <p>t(9;22)</p> Signup and view all the answers

    Which variant of the BCR::ABL1 transcript is associated with a poor prognosis?

    <p>e1a2/a3</p> Signup and view all the answers

    What is one characteristic that differentiates leukemoid reactions from CML?

    <p>WBC count typically less than 50 × 10^9/L</p> Signup and view all the answers

    What type of conditions can present with splenomegaly and neutrophilia?

    <p>Agnogenic myeloid metaplasia</p> Signup and view all the answers

    Which cytogenetic abnormality is particularly associated with poor prognosis in CML?

    <p>i(17)(q10)-7/del17q</p> Signup and view all the answers

    What is the most consistent physical sign in patients with chronic myeloid leukemia (CML)?

    <p>Splenomegaly</p> Signup and view all the answers

    What is a common characteristic of Polycythemia vera?

    <p>Normal hemoglobin levels</p> Signup and view all the answers

    Which symptom is commonly associated with leukostatic effects in chronic myeloid leukemia?

    <p>Drowsiness</p> Signup and view all the answers

    What is the median platelet count in about 50% of patients with chronic myeloid leukemia?

    <p>400 × 10^9/L</p> Signup and view all the answers

    What is a common laboratory finding in patients at the time of diagnosis of chronic myeloid leukemia?

    <p>Leukocytosis greater than 25 × 10^9/L</p> Signup and view all the answers

    In chronic myeloid leukemia, which of the following cell types typically shows a left shift in blood findings?

    <p>Neutrophils</p> Signup and view all the answers

    How is the absolute eosinophil count typically affected in chronic myeloid leukemia?

    <p>It is nearly always increased.</p> Signup and view all the answers

    What classifies the presentation of CML in blast phase (CML-BP)?

    <p>Acute leukemia with worsening constitutional symptoms</p> Signup and view all the answers

    What characterizes the peripheral blood smear in chronic-phase CML?

    <p>Markedly granulocytic leukocytosis without increase in blasts</p> Signup and view all the answers

    What is the median survival rate for patients typically unresponsive to TKI therapy?

    <p>2–3 years</p> Signup and view all the answers

    What is the frontline therapy recommended for chronic myeloid leukemia (CML) chronic phase?

    <p>Imatinib, Dasatinib, Bosutinib, or Nilotinib</p> Signup and view all the answers

    Which mutation is commonly associated with Myelodysplastic Syndromes/Myeloproliferative Neoplasms (MDS/MPN)?

    <p>SF3B1</p> Signup and view all the answers

    What does MR4 in molecular response testing indicate?

    <p>≤ 1 cell of BCR-ABL1 per 10,000 cells</p> Signup and view all the answers

    Which TKI is considered a third-line therapy for CML?

    <p>Asciminib</p> Signup and view all the answers

    What is a notable effect of second-generation TKIs on patient response?

    <p>They lead to higher rates of early optimal responses.</p> Signup and view all the answers

    Which follow-up method is recommended to monitor treatment response after starting therapy?

    <p>Bone marrow study at 3, 6, and 12 months</p> Signup and view all the answers

    What is the primary mechanism of action of TKIs in the treatment of CML?

    <p>They block ATP interactions with BCR::ABL1 oncoprotein.</p> Signup and view all the answers

    Study Notes

    Chronic Myeloid Leukemia (CML)

    • CML is a myeloproliferative neoplasm (MPN) caused by a genetic translocation between the ABL1 gene on chromosome 9 and the BCR gene on chromosome 22.
    • This translocation leads to the expression of the BCR-ABL1 fusion protein, a constitutively active tyrosine kinase, causing aberrant cell growth and survival.
    • CML prevalence is two cases/100,000, accounting for 15% of newly diagnosed leukemia cases in adults, with a slight male predominance.
    • Tyrosine kinase inhibitors (TKIs) have dramatically reduced mortality rates to 2-3% per year.

    CML Stages

    • Chronic Phase (CP): Asymptomatic in 50% of cases, common signs include fatigue, weight loss, splenomegaly, and anemia due to excessive immature myeloid cells.
    • Blast Phase (BP): Characterized by >20% blasts in the bone marrow, presents as acute leukemia, and has a much poorer prognosis compared to CP.
    • Accelerated Phase (AP) is no longer considered a separate stage, categorized as high-risk CP.

    Diagnosis and Differential Diagnosis

    • Peripheral blood smear: Shows neutrophilia, myelocyte bulge, basophilia, and lack of dysplastic features. No increased blasts in the chronic phase.
    • Cytogenetics: Ph chromosome (9;22) is detected in 90% of cases.
    • Molecular testing: Detects the BCR-ABL1 fusion gene transcript, with different variants impacting prognosis.
    • Differential Diagnosis: Includes leukemoid reactions, other MPNs, and MDS syndromes.
    • Molecular Testing: Used to distinguish atypical CML from other conditions by detecting non-ABL1 mutations (e.g., SETBP1, SF3B1, CSF3R)

    Treatment

    • First-line therapy: TKIs (imatinib, dasatinib, bosutinib, nilotinib) are the standard of care for CML-CP.
    • Second-line therapy: Second-generation TKIs (bosutinib, dasatinib, nilotinib, ponatinib) are used if resistance or intolerance develops to first-line TKIs.
    • Third-line therapy: Ponatinib, asciminib, and allogeneic hematopoietic stem cell transplantation (Allo-HSCT) are options for patients with resistance to multiple TKIs.
    • Allo-HSCT: Is not recommended as frontline therapy due to the efficacy of TKIs.

    Monitoring Response to Therapy

    • Bone marrow studies: Recommended at 3, 6, and 12 months after initiating therapy to assess response and disease progression.
    • Molecular response (MR) testing: Evaluates the level of BCR-ABL1 transcripts in blood or bone marrow.
    • MR levels:
      • MR1: BCR-ABL1 ≤ 10 cells per 100 cells
      • MR2: BCR-ABL1 ≤ 1 cells per 100 cells
      • MR3 (Major Molecular Response): BCR-ABL1 ≤ 1 cells per 1,000 cells
      • MR4 (Deep Molecular Response): BCR-ABL1 ≤ 1 cells per 10,000 cells
      • MR5 (Deep Molecular Response): BCR-ABL1 ≤ 1 cells per 100,000 cells
    • Treatment-free remission (TFR): A potential treatment strategy for patients achieving deep molecular response after several years of TKI therapy.

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    Chronic Myeloid Leukemia (CML): 2025 Update PDF

    Description

    This quiz covers the essential aspects of Chronic Myeloid Leukemia (CML), including its genetic basis, prevalence, treatment options, and stages. Participants will learn about the BCR-ABL1 fusion protein and the implications of tyrosine kinase inhibitors on patient outcomes. Engage with the content to enhance your understanding of this myeloproliferative neoplasm.

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