Leukaemia Flashcards
How are leukaemias classified?
Based on lineage: - myeloid - lymphoid Based on developmental stage: - acute blastic (blast cells) - chronic cytic (differentiated cells) Based on anatomical site: - blood --> leaukaemia - lymph node with lymphoid malignancy --> lymphoma
What is a clone?
Population of cells derived from a single parent cell
How do clones differ in normal haematopoesis and malignant haematopoesis?
Normal haematopoesis = polyclonal
Malignant = monoclonal
What are the four different types of leukaemia?
Acute lymphoblastic (ALL) Acute myeloid (AML) Chronic lymphocytic (CLL) Chronic myeloid (CML)
How are acute leukaemias defined?
Rapidly progressive clonal malignancy of the marrow/blood with maturation defects
–> excess of blasts (>20%) in either peripheral blood or bone marrow
Which leukaemia is most common in childhood?
ALL
What are the differences in pathology and epidemiology of ALL and AML?
ALL:
- proliferation of lymphocyte progenitors
- most common in children
AML:
- proliferation of granulocyte progenitors
- most common in elderly (>60)
Which clinical features are common to both acute leukaemias?
Pancytopenia (anaemia, infection, bleeding) Bone pain Organ infiltration: - hepatosplenomegaly - lymphadenopathy - gum hypertrophy - skin nodules - mediastinal mass (enlarged thymus)
Which additional features may be seen in ALL?
CNS: CN palsy, papilloedema, meningism
Testes: unilateral swelling
What would be seen on blood film in acute laeukaemia
Raised blasts with high nuclear:cytoplasmic ratio
- lymphoblasts in ALL
- myeloblasts containing Auer rods in AML
How is acute leukaemia diagnosed?
Bone marrow biopsy/aspirate:
- blast cells > 20% confirms diagnosis
- immunophenotyping to identify lineage subtype
What is the management for acute leukaemia?
Multi-agent chemotherapy:
- 6-8 months in AML
- up to 3 years in ALL
What are the complications of chemotherapy?
Marrow suppression (anaemia, neutropenia, bleeding)
Nausea + vomiting
Hair loss
Liver, renal dysfunction (check LFTs + U&Es first)
Tumour lysis syndrome
Infertility esp. males (sperm bank before)
Cardiomyopathy/HF
Why is neutropenia concerning in patients on chemotherapy?
Neutropenic sepsis
–> esp gram -ve bacterial or fungal
What is the most common leukaemia in adults?
CLL
What causes CLL?
Proliferation of mature B cells
How does CLL differ from lymphoma?
Accumulation of B cells in CLL is mainly in the blood and bone marrow
In lymphoma, mainly in lymph nodes
What are the clinical features of CLL?
90% asymptomatic at presentation (incidental finding of raised WBCs)
Lymphadenopathy, splenomegaly, hepatomegaly
Symptomatic disease:
- pancytopenia from marrow infiltration
- weight loss, sweats, anorexia
- recurrent infections due to dysfunctional lymphocytes causing low Ig
What would be seen on FBC in CLL?
Raised WBC with lymphocytes > 5000
Low platelets
Anaemia (due to marrow failure or DAT+ve haemolytic anaemia)
What would be seen on blood film in CLL?
Lymphocytosis
Smudge cells
How is CLL staged?
Binet system (A-C) - based on WBC, Hb + clinical findings
What is the management for asymptomatic CLL?
Watchful waiting:
- 3 monthly FBC, flow cytometry + examination
What is the management for symptomatic CLL?
Chemotherapy
What are some of the complications of CLL?
Recurrent infections (due to treatment or disease)
Richter transformation to high grade Non-Hodgkins lymphoma
Hyperviscosity syndrome
Which cells are involved in CML?
Clonal proliferation of myeloid stem cells which differentiate into granulocytes
Which mutation is involved in 98% of CML cases?
Philadelphia chromosome encoding p210 tyrosine kinase
What are the clinical features of CML?
Often asymptomatic
Tired, malaise, fever, weight loss, night sweats
Splenomegaly –> LUQ discomfort/early satiety
Features of cytopenia
Gout/arthralgia (raised urate)
What would be seen on FBC and blood film in CML?
Very high WBCs, can be > 100
Anaemia
Film: raised granulocytes esp. neutrophils
How is CML diagnosed?
Bone marrow biopsy: granulocytic hyperplasia
Cytogenetics (blood or marrow) and FISH for Philadelphia chromosome
What is the management for CML?
Imatinab –> inhibits p210 tyrosine kinase and induces long term remission
What are the side effects of imatinab?
Cramps
Oedema
Rash
Diarrhoea
