Leukaemia Flashcards
State the five key aspects of normal haemopoiesis
Self-renewal Proliferation Differentiation Maturation Apoptosis
How does malignancy arise?
Increased proliferation
Lack of differentiation
Lack of maturation
Lack of apoptosis
How does acute leukaemia arise?
Proliferation of abnormal progenitors with block of differentiation/maturation
How does chronic myeloid leukaemia arise?
Proliferation of myeloid cells but no differentiation/maturation block
What causes leukaemia?
Multifactorial
Acquired somatic mutations in regulatory genes (driver mutations)
What do driver mutations do?
Select clones and confer a growth advantage
What is a clone?
Population of cells derived from a single parent cell
Is malignancy polyclonal or monoclonal?
Monoclonal
Name four factors that help determine the subtype of malignancy
Lineage
Developmental stage within lineage
Anatomical site
Histology/presentation
What are the two key lineages?
Myeloid
Lymphoid
What are the two main anatomical site of haematological malignancy?
Blood - leukaemia
Lymph nodes - lymphoma
Describe the characteristics of a high grade tumour
Large cells High nucleus to cytoplasm ratio Prominent nucleoli Rapid proliferation Rapid progression of symptoms
In acute leukaemia what type of cells are in excess?
Blasts
Name two types of acute leukaemia
Acute myeloid
Acute lymphoblastic
Describe ALL
Disease of primitive lymphoid cells - lymphoblasts. Most common childhood cancer
How will ALL present?
Marrow failure - anaemia, infection, bleeding
Leukaemia effects
Bone pain
What is meant by leukaemic effects?
High count with obstruction of circulation and involvement of areas outwit the marrow/blood
Name two common extra-medullary sites
CNS, testes
Describe AML
More common in elderly >60 years old
De novo or secondary
How does AML present?
Similar to ALL with dominant marrow failure
Name two subgroups of AML
DIC in acute promyelocytic leukaemia
Gum infiltration
What investigations should be done in acute leukaemia?
Blood count and film Coagulation screen D dimer and fibrinogen - DIC Bone marrow aspirate Immunophenotyping Cytogenic analysis Trephine biopsy
What will a blood film of leukaemia show?
Reduced Hb Neutrophils Platelets Increased WCC Blasts Aner Rods
What are Aner rods?
Cytoplasmic inclusions seen in AML
How does immunophenotyping work?
Lineage specific proteins on cell surface
Definitive diagnosis - important for treatment
How is leukaemia treated?
Multi-agent chemotherapy
How long may ALL last?
2-3 years
How is AML treated?
2-4 cycles of chemo followed by 2-4 weeks recovery. Intensive therapy requires prolonged hospitalisation
Name the type of long term central venous access used
Hickman Line
Where is the tip of Hickman Line?
SVC - right atrium junction
What are the complications of leukaemia treatment?
Anaemia
Neutropenia - infections
Thrombocytopenia
Which infections are common in leukaemia patients?
Gram negative bacteria from large bowel can cause fulminant life threatening sepsis
Fungal infections can also occur
After culture what must be done in leukaemia patients with infection?
Broad spec antibiotics
How will thrombocytopenia present and what is the treatment?
Bleeding
Petechiae
Requires platelet transfusion
Name the side effects of chemotherapy
Nausea/vomiting Hair loss Liver/renal dysfunction Tumour lysis syndrome Infection (bacterial, fungal, protozoal - PJC) Late effects - infertility/cardiotoxic