Haematology - leukaemia Flashcards
What is leukaemia?
A cancer of a particular line of stem cells in the bone marrow
Causes unregulated production of certain types of blood cells
Pathophysiology of leukaemia
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).
Presentation of leukaemia
Non-specific
Fatigue
Fever
Pallor - due to anaemia
Petechiae and abnormal bruising due to thrombocytopaenia
Abnormal bleeding
LNs raised
Hepatosplenomegaly
Differential diagnosis of petechiae
Petechiae caused by bleeding under the skin due to low platelets
Leukaemia
Meningococcal septicaemia
Vasculitis
HSP
ITP
Non-accidental injury
Diagnosing leukaemia
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)
What is the pathology in ALL?
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.
How does ALL present and who does it typically present in?
Most common cancer in children but can also affect adults over 45
Often also associated with Down’s syndrome
What are the blood film and genetic findings in ALL?
Blast cells on blood film (lymphoblasts)
Can be associated with Philadelphia chromosome (more of an association in CML)
What is chronic lymphocytic leukaemia pathology?
Chronic proliferation of a single type of well differentiated lymphocyte, usually B-lymphocytes
How does CLL present?
Often asymptomatic - may be an incidental finding of raised WBC on bloods
Infections
Anaemia
Bleeding
Weight loss
Most common adult leukaemia
What are the blood film findings in CLL?
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.
What are some complications of CLL?
Transformation into high-grade non-Hodgkin’s lymphoma (Richter’s transformation)
Warm autoimmune haemolytic anaemia
What is CML pathology?
Philadelphia chromosome, which is a translocation of genes between chromosome 9 and 22
(t(9:22) translocation)
Presentation of CML
Anaemia: lethargy
Weight loss and sweating are common
Splenomegaly often marked → abdo discomfort
What are some complications of CML?
May transform into an acute leukaemia e.g. AML (80%), ALL (20%)
What are the phases of CML?
Chronic phase - many years often asymptomatic
Accelerated/blast phase - higher proportion of blast cells. Progressive symptoms often unresponsive to therapy/fatal
What is the pathology in AML?
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
What will a blood film show in AML?
High proportion of blast cells (myeloblasts)
These blast cells have rods in their cytoplasm called Auer rods
What is a subtype of AML to be aware of?
Acute promyelocytic leukaemia
Can present with DIC - bleeding gums and low fibrinogen on bloods
General management of leukaemias
Oncology MDT
Primarily treated with chemotherapy and steroids
Other therapies include radiotherapy, bone marrow transplant and surgery
Complications of chemotherapy
Tumour lysis syndrome
Infections due to immunodeficiency
Failure of the chemotherapy
Stunted growth and development in children
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity
What is the first line treatment for CML?
Imatinib (tyrosine kinase inhibitor)
Tyrosine kinase enzymes are produced in CML and drive cell turnover - target of these drugs
What is tumour lysis syndrome?
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.
