Podcast
Questions and Answers
Which mutation is known as the 'gatekeeper' mutation that causes resistance to all currently available TKIs except ponatinib and asciminib?
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?
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?
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?
What is the median survival for CML-AP that evolves from CML-CP?
Which gene is NOT mentioned as one of the most frequently mutated in advanced-stage CML?
Which gene is NOT mentioned as one of the most frequently mutated in advanced-stage CML?
What is the primary genetic change associated with chronic myeloid leukemia (CML)?
What is the primary genetic change associated with chronic myeloid leukemia (CML)?
What percentage of newly diagnosed leukemia cases in adults does CML account for?
What percentage of newly diagnosed leukemia cases in adults does CML account for?
What is a common initial manifestation of chronic phase (CML-CP)?
What is a common initial manifestation of chronic phase (CML-CP)?
Which of the following statements about CML is false?
Which of the following statements about CML is false?
What role does the BCR::ABL1 oncoprotein play in CML?
What role does the BCR::ABL1 oncoprotein play in CML?
Which phase of CML is characterized by the highest number of symptomatic patients?
Which phase of CML is characterized by the highest number of symptomatic patients?
Which of the following treatment approaches is used to manage resistance to TKIs in CML?
Which of the following treatment approaches is used to manage resistance to TKIs in CML?
What causes the increased proliferation of CML cells?
What causes the increased proliferation of CML cells?
What percentage of patients typically have the Ph chromosome?
What percentage of patients typically have the Ph chromosome?
Which is a common additional chromosomal abnormality seen in Ph-positive cells?
Which is a common additional chromosomal abnormality seen in Ph-positive cells?
What is the typical translocation associated with Ph-positive CML?
What is the typical translocation associated with Ph-positive CML?
Which variant of the BCR::ABL1 transcript is associated with a poor prognosis?
Which variant of the BCR::ABL1 transcript is associated with a poor prognosis?
What is one characteristic that differentiates leukemoid reactions from CML?
What is one characteristic that differentiates leukemoid reactions from CML?
What type of conditions can present with splenomegaly and neutrophilia?
What type of conditions can present with splenomegaly and neutrophilia?
Which cytogenetic abnormality is particularly associated with poor prognosis in CML?
Which cytogenetic abnormality is particularly associated with poor prognosis in CML?
What is the most consistent physical sign in patients with chronic myeloid leukemia (CML)?
What is the most consistent physical sign in patients with chronic myeloid leukemia (CML)?
What is a common characteristic of Polycythemia vera?
What is a common characteristic of Polycythemia vera?
Which symptom is commonly associated with leukostatic effects in chronic myeloid leukemia?
Which symptom is commonly associated with leukostatic effects in chronic myeloid leukemia?
What is the median platelet count in about 50% of patients with chronic myeloid leukemia?
What is the median platelet count in about 50% of patients with chronic myeloid leukemia?
What is a common laboratory finding in patients at the time of diagnosis of chronic myeloid leukemia?
What is a common laboratory finding in patients at the time of diagnosis of chronic myeloid leukemia?
In chronic myeloid leukemia, which of the following cell types typically shows a left shift in blood findings?
In chronic myeloid leukemia, which of the following cell types typically shows a left shift in blood findings?
How is the absolute eosinophil count typically affected in chronic myeloid leukemia?
How is the absolute eosinophil count typically affected in chronic myeloid leukemia?
What classifies the presentation of CML in blast phase (CML-BP)?
What classifies the presentation of CML in blast phase (CML-BP)?
What characterizes the peripheral blood smear in chronic-phase CML?
What characterizes the peripheral blood smear in chronic-phase CML?
What is the median survival rate for patients typically unresponsive to TKI therapy?
What is the median survival rate for patients typically unresponsive to TKI therapy?
What is the frontline therapy recommended for chronic myeloid leukemia (CML) chronic phase?
What is the frontline therapy recommended for chronic myeloid leukemia (CML) chronic phase?
Which mutation is commonly associated with Myelodysplastic Syndromes/Myeloproliferative Neoplasms (MDS/MPN)?
Which mutation is commonly associated with Myelodysplastic Syndromes/Myeloproliferative Neoplasms (MDS/MPN)?
What does MR4 in molecular response testing indicate?
What does MR4 in molecular response testing indicate?
Which TKI is considered a third-line therapy for CML?
Which TKI is considered a third-line therapy for CML?
What is a notable effect of second-generation TKIs on patient response?
What is a notable effect of second-generation TKIs on patient response?
Which follow-up method is recommended to monitor treatment response after starting therapy?
Which follow-up method is recommended to monitor treatment response after starting therapy?
What is the primary mechanism of action of TKIs in the treatment of CML?
What is the primary mechanism of action of TKIs in the treatment of CML?
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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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.
