Leukaemia: CLL, CML

Question 1

What is CLL?

Answer 1

A haematologic malignancy characterized by the accumulation of mature monoclonal B lymphocytes in the blood, bone marrow, and lymphoid tissues.

These abnormal B cells are often slow-growing and crowd out healthy blood cells.

Question 2

Presentation of CLL?

Answer 2

B symptoms
Non-tender symmetrical lymphadenopathy
Hepatosplenomegaly

Signs of marrow failure (infection, anaemia and bleeding) are less common than in acute leukaemias.

Question 3

IVx of CLL?

Answer 3

Blood film -SMUDGE CELLS
FBC: incidental lymphocytosis

Immunophenotype:
CD5 and CD23 positive
FMC negative
CD22 and surface immunoglobulin weak

Direct antiglobulin test can be positive.

Hypogammaglobulinaemia

Bone marrow:
- lymphocytic infiltration of mature lymphocytes

Question 4

Management of CLL?

Answer 4

Targeted pathway inhibitors
1st line: VENETOCLAX (if no no co-morbidities and TP53 intact, +/- mutated IGHV mutated status)

Fit patients with TP53 mutational disruption or any IGHV mutated status:
1st line: Acalabrutinib +/- Obinutuzumab or upfront Ibrutinib

Allogeneic stem cell transplant (failed 2 tx or have Richter’s transformation)

Question 5

What is CML?

Answer 5

A myeloproliferative neoplasm characterised by the presence of the Philadelphia chromosome (9 and 22).

Question 6

Presentation of CML?

Answer 6

Weight loss
Tiredness
Fever
Sweating

Common:
- Massive splenomegaly
- Bleeding (due to thrombocytopenia)
- Gout

High WCC (hyperleukocytosis)
- Visual disturbance
- Confusion
- Priapism
- Deafness

Hypermetabolism

Question 7

IVx of CML?

Answer 7

Blood test
- leucocytosis
- raised myeloid cells (monocytes, basophils, eosinophilia, neutrophils)
- neutrophils -LEFT SHIFT and earlier myeloid cells
- anaemia
- deranged platelet count

Blood film
- depends on phase of CML
- chronic (leucocytosis with immature white and red blood cells)
- accelerated (>15% blast cells, promyelocytes and basophils)
- blastic phase (>20% blast cells)

Bone marrow
Marrow hyperplasia
Increased reticulin (fibrosis)
Granulocytic predominance

High vitamin B12 levels

BCR–ABL/Philadelphia chromosome -DIAGNOSTIC MARKER

Question 8

Management of CML?

Answer 8

tyrosine kinase inhibitors (eg. imatinib)
- Haematological remission
- Cytogenetic remission
- Molecular remission

Hydroxycarbamide -to normalise blood count

Monitoring/screening mutation of BCR–ABL levels

Stem cell transplantation

Question 9

What is ALL associated with?

Answer 9

ALL is the most common leukaemia in children and is associated with Down syndrome.

Question 10

What is with CLL associated with?

Answer 10

CLL is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells.

Question 11

What is CML associated with?

Answer 11

CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome.

Question 12

What is AML associated with?

Answer 12

AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods.