CML Flashcards
Describe the genetic pathophysiology of CML [3]
presence of the BCR-ABL fusion gene:
- results from a reciprocal translocation between chromosomes 9 and 22
- known as the Philadelphia (Ph) chromosome
- BCR-ABL fusion protein drives uncontrolled cell growth and proliferation, leading to CML.
Describe the typical presentation of CML [+]
- Fatigue/lethargy
- Night sweats
- Weight loss
- Splenomegaly
- Generalised lymphadenopathy
- Symptoms and signs of anaemia
- Altered mental state: due to leucostasis
- Signs secondary to hyperviscosity: a cerebrovascular events; priparism; opthalmic complications
How do you diagose CML? [2]
Cytogenetics:
- identification of Ph chromosome (95%)
- Ph chromosome is not identified on cytogenetics in around 5%. In these patients fluorescent in situ hybridisation (FISH)
What findings for CML would you find on a FBC? [3]
Leucocytosis, typically 20-60 * 109 /L
- The differential may demonstrate increased cell numbers from the myeloid lineage of leucocytes.
Thrombocytosis or thrombocytopenia may occur
Anaemia is a common finding, often normochromic and normocytic, but depending on haematinics, other abnormalities e.g. microcytic, hypochromic anaemia of iron deficiency may also be found.
Describe the different phases of CML [3]
1. Chronic phase
- The vast majority (> 85%) present in the chronic phase of disease.
- Clinical features are typically non-specific and include fatigue, weight loss and night sweats
2. Accelerated phase
- abnormal blast cells take up a high proportion (10-20%) of the bone marrow and blood cells.
- In the accelerated phase symptoms and features become more apparent and severe:
- anaemia, thrombocytopenia and immunodeficiency.
- Disease is more difficult to treat and outcomes worse.
3. Blast crisis
- This phase resembles an acute leukaemia with the rapid expansion of blasts
- pancytopenia occurs
- Without treatment survival is typically a few months.
What defines if CML is in the accelerated phase? [4]
- Blasts in blood or marrow 15–29%, or blasts plus promyelocytes in blood or marrow >30%, with blasts < 30%
- Basophils in blood ≥ 20%
- Persistent thrombocytopenia (< 100 × 109/L) unrelated to therapy
- Clonal chromosome abnormalities in Ph+ cells, major route, on treatment
What defines if CML is in blast crisis phase? [2]
Blasts in blood or marrow ≥30%
Extramedullary blast proliferation, apart from spleen
What are the three broad goals of CML managment? [3]
Haematologic remission
- defined as a normal full blood cell count and physical examination (no evidence of underlying organomegaly).
Cytogenetic remission
- defined as seeing 0% Philadelphia chromosome-positive (Ph+) cells on chromosomal analysis.
Molecular remission
- defined as negative polymerase chain reaction result for the mutational BCR/ABL mRNA.
Describe the treatment regime for CML in the:
- Chronic phase
- Advanced phase
- B
Chronic phase: tyrosine kinase inhibitors
- 1st line: imatinib
- dasatinib
- nilotinib
Advanced:
- Ideally all patients should be treated as part of a clinical trial
Blast phase:
- start / switch a tyrosine kinase inhibitor with induction chemotherapy; followed by stem cell transplant
What drug can be given to reduce the risk of tumour lysis syndrome [1]
allopurinol
State two side effects of Imatinib treatment [2]
GI upset
Irreversible kidney damage
Increased risk of CV or thrombotic events (esp. in chronic phase)
Myelosuppression
QT prolongation
a. How frequently should monitoring of BCR-ABL transcript levels be performed during the first year of treatment for CML?
- A. Every 3 months
- B. Every 6 months
- C. Once a year
- D. Only in case of symptoms
a. How frequently should monitoring of BCR-ABL transcript levels be performed during the first year of treatment for CML?
- A. Every 3 months
- B. Every 6 months
- C. Once a year
- D. Only in case of symptoms
a. Regular monitoring of which parameter is crucial for assessing the response to treatment and detecting relapse in CML?
A. Hemoglobin levels
B. Platelet count
C. BCR-ABL transcript levels
D. Liver function tests
a. Regular monitoring of which parameter is crucial for assessing the response to treatment and detecting relapse in CML?
A. Hemoglobin levels
B. Platelet count
C. BCR-ABL transcript levels
D. Liver function tests
a. Which of the following is a potential complication of tyrosine kinase inhibitor (TKI) therapy in CML?
A. Hepatotoxicity
B. Cardiotoxicity
C. Myelosuppression
D. All of the above
a. Which of the following is a potential complication of tyrosine kinase inhibitor (TKI) therapy in CML?
A. Hepatotoxicity
B. Cardiotoxicity
C. Myelosuppression
D. All of the above
a. What is the characteristic molecular marker for CML?
A. BCR-ABL fusion gene
B. FLT3-ITD mutation
C. JAK2 mutation
D. MPL mutation
a. What is the characteristic molecular marker for CML?
A. BCR-ABL fusion gene
B. FLT3-ITD mutation
C. JAK2 mutation
D. MPL mutation
