Haematology - leukaemia

Question 1

What is leukaemia?

Answer 1

A cancer of a particular line of stem cells in the bone marrow

Causes unregulated production of certain types of blood cells

Question 2

Pathophysiology of leukaemia

Answer 2

A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.

The excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types. This results in a pancytopenia, which is a combination of low red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia).

Question 3

Presentation of leukaemia

Answer 3

Non-specific

Fatigue

Fever

Pallor - due to anaemia

Petechiae and abnormal bruising due to thrombocytopaenia

Abnormal bleeding

LNs raised

Hepatosplenomegaly

Question 4

Differential diagnosis of petechiae

Answer 4

Petechiae caused by bleeding under the skin due to low platelets

Leukaemia

Meningococcal septicaemia

Vasculitis

HSP

ITP

Non-accidental injury

Question 5

Diagnosing leukaemia

Answer 5

FBC - initial investigation

Blood film - to look for abnormal cells and inclusions

LDH - often raised in leukaemia but not specific

Bone marrow biopsy

LN biopsy - can be used to assess lymph node involvement or investigate for lymphoma

Staging CT - can be used to assess lymph node involvement or investigate for lymphoma

(A CXR may show infection or mediastinal lymphadenopathy)

Question 6

What is the pathology in ALL?

Answer 6

Malignant change in one of the lymphocyte precursor cells

Causes acute proliferation of single type of lymphocyte - usually B-lymphocytes

Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia.

Question 7

How does ALL present and who does it typically present in?

Answer 7

Most common cancer in children but can also affect adults over 45

Often also associated with Down’s syndrome

Question 8

What are the blood film and genetic findings in ALL?

Answer 8

Blast cells on blood film (lymphoblasts)

Can be associated with Philadelphia chromosome (more of an association in CML)

Question 9

What is chronic lymphocytic leukaemia pathology?

Answer 9

Chronic proliferation of a single type of well differentiated lymphocyte, usually B-lymphocytes

Question 10

How does CLL present?

Answer 10

Often asymptomatic - may be an incidental finding of raised WBC on bloods

Infections

Anaemia

Bleeding

Weight loss

Most common adult leukaemia

Question 11

What are the blood film findings in CLL?

Answer 11

Smear or smudge cells

These occur during the process of preparing the blood film where aged or fragile white blood cells rupture and leave a smudge on the film.

Question 12

What are some complications of CLL?

Answer 12

Transformation into high-grade non-Hodgkin’s lymphoma (Richter’s transformation)

Warm autoimmune haemolytic anaemia

Question 13

What is CML pathology?

Answer 13

Philadelphia chromosome, which is a translocation of genes between chromosome 9 and 22
(t(9:22) translocation)

Question 14

Presentation of CML

Answer 14

Anaemia: lethargy

Weight loss and sweating are common

Splenomegaly often marked → abdo discomfort

Question 15

What are some complications of CML?

Answer 15

May transform into an acute leukaemia e.g. AML (80%), ALL (20%)

Question 16

What are the phases of CML?

Answer 16

Chronic phase - many years often asymptomatic

Accelerated/blast phase - higher proportion of blast cells. Progressive symptoms often unresponsive to therapy/fatal

Question 17

What is the pathology in AML?

Answer 17

Most common acute leukaemia in adults

It can present at any age but normally presents from middle age onwards.

It can be the result of a transformation from a myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis

Can present with DIC - bleeding gums and low fibrinogen on bloods - Acute promyelocytic leukaemia

Question 18

What will a blood film show in AML?

Answer 18

High proportion of blast cells (myeloblasts)

These blast cells have rods in their cytoplasm called Auer rods

Question 19

What is a subtype of AML to be aware of?

Answer 19

Acute promyelocytic leukaemia

Can present with DIC - bleeding gums and low fibrinogen on bloods

Question 20

General management of leukaemias

Answer 20

Oncology MDT

Primarily treated with chemotherapy and steroids

Other therapies include radiotherapy, bone marrow transplant and surgery

Question 21

Complications of chemotherapy

Answer 21

Tumour lysis syndrome

Infections due to immunodeficiency

Failure of the chemotherapy

Stunted growth and development in children

Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity

Question 22

What is the first line treatment for CML?

Answer 22

Imatinib (tyrosine kinase inhibitor)

Tyrosine kinase enzymes are produced in CML and drive cell turnover - target of these drugs

Question 23

What is tumour lysis syndrome?

Answer 23

Caused by the release of uric acid from cells being destroyed by chemo

Uric acid can form crystals in the tubules of the kidney and cause AKI

Prevented by giving patients with AML/ALL IV fluids and starting allopurinol

Other chemicals such as potassium and phosphate are also released so these need to be monitored and treated appropriately. High phosphate can lead to low calcium, which can have an adverse effect, so calcium is also monitored.