Chronic Myeloid Leukemia Flashcards
Chronic myeloid leukaemia can be classified as both a ___________ and a ____________.
It is characterized by __________________ in the peripheral blood and an excess of myelocytes. It is a malignancy of pluripotent stem cell.
More than 95% of CML show _____________.
The median age of onset is 55-60 years, and the incidence of CML is about 1.6 per 100,000
Mainly in middle aged adults
If not initially cured, will be followed eventually by ‘blast crisis’ transformation to ____________ or _____________ with death in a median of 3–4 years.
leukemia
myeloproliferative disorder;
large numbers of differentiated neutrophils;
Philadelphia (Ph) chromosome;
acute leukaemia (75% myeloid, 25% lymphoid) or myelofibrosis
Philadelphia chromosome (Ph): reciprocal translocation between __________________, forming a novel ___________ gene that is transcribed into a novel oncoprotein with tyrosine kinase activity. This protein leads to increased cell cycling and a failure of apoptosis.
The ______________ is a target for therapy. Inhibitors of the ATP-binding site on this tyrosine kinase have therefore been developed to treat CML.
chromosome 22 and chromosome 9
BCR-ABL
tyrosine kinase (TK) BCR–ABL
What are the clinical features of CML?
Increased Neutrophils, Eosinophils, Basophils, Platelets
Anemia
Hypermetabolic state: Weight loss, lethargy, night sweats (similar to IMF since both are severe forms of Myelodysplasia)
- Due to the sheer number of cells produced
- Across all Leukemias and MPN, the 2 diseases with the greatest degree of CHRONIC increase in cell production + turnover = CML and IMF
- Other leukemias such as CLL that MAY have hypermetabolic state 🡪 usually is only a sign of SEVERE grade that warrants immediate treatment
- Note that this is different from B symptoms: Fever, Night Swears, LOW 🡪 which is seen in HL
Splenomegaly** – massive 🡪 due to extramedullary haematopoiesis; may look pregnancy! 🡪 abdominal discomfort
Gout (increase in uric acid due to high cellular turnover)
Incidental abnormal FBC
[Clinical Course of CML]
Chronic Phase
- 80% of patients with CML are diagnosed in the chronic phase.
- In the chronic phase, there are ____________ in the blood and bone marrow.
- It can last a ________________ and can usually be controlled with medication.
- Nearly 80% of patients with CML will progress from the chronic phase to the accelerated phase.
Accelerated Phase
- ________ of the blood and bone marrow are blast cells.
- Patients may have ____________, increasing number of basophils or blasts in peripheral blood/BM, increased white cell count refractory to treatment or additional cytogenetic abnormalities
Blast crisis (AML) - \_\_\_\_\_\_\_\_\_\_\_\_\_ in the blood and bone marrow 🡪 transformation to AML
<5% blasts ;
few months to 4-5 years;
10-19%
enlarging spleen
> =20% blasts
What are the findings of CML on peripheral blood film?
Neutrophils, eosinophils, basophils, platelets can all be increased as well as proliferation of early myeloid cells
Looks more like a bone marrow (plentiful myelocytes, promyelocytes, eosinophils, basophils, platelets)
What are the findings of CML on bone marrow?
Cells densely packed with less fat spaces
What is the cytogenic findings of CML?
Philadelphia chromosome
What is the management of CML?
First line therapy: Imatinib (blocks tyrosine kinase activity by competing with ATP binding, leads to both haematological response and cytogenetic response (Ph chromosome no longer present))
- 95% haematological response
- Up to 85% cytogenetic response
- 9% relapse at 18 months
Definitive Mx: Allogenic hematopoietic stem cell transplant
- Consider if in Blast crisis or resistance to all TKI
- High risk but potentially curative!