Chronic Myeloid Leukemia

Question 1

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.

Answer 1

leukemia

myeloproliferative disorder;

large numbers of differentiated neutrophils;

Philadelphia (Ph) chromosome;

acute leukaemia (75% myeloid, 25% lymphoid) or myelofibrosis

Question 2

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.

Answer 2

chromosome 22 and chromosome 9

BCR-ABL

tyrosine kinase (TK) BCR–ABL

Question 3

What are the clinical features of CML?

Answer 3

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

Question 4

[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

Answer 4

<5% blasts ;

few months to 4-5 years;

10-19%

enlarging spleen

> =20% blasts

Question 5

What are the findings of CML on peripheral blood film?

Answer 5

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)

Question 6

What are the findings of CML on bone marrow?

Answer 6

Cells densely packed with less fat spaces

Question 7

What is the cytogenic findings of CML?

Answer 7

Philadelphia chromosome

Question 8

What is the management of CML?

Answer 8

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!