Leukaemia Flashcards
What is leukaemia?
Cancer of the stem cells in the bone marrow
Leading to unregulated production of blood cells
What are the different types of leukaemia that affect children?
Acute lymphoblastic leukaemia (most common)
Acute myeloid leukaemia
Chronic myeloid leukaemia
What age are most patients affected by leukaemia?
60-70 in most patients
Acute lymphoblastic leukaemia most commonly under 5
What are the key differentiating features between different types of leukaemia?
AML
Transformation from a myeloproliferative disorder
Auer rods
CML
3 phases including a long chronic phase
Philadelphia chromosome
ALL
Children (better prognosis in girls)
Down Syndrome
CLL
Warm haemolytic anaemia
Richter’s transformation cells
Smudge cells
What is the pathophysiology of leukaemia
Mutation in precursor cells, leads to excessive production of abnormal white cells
Excessive production can lead to suppression of other cell lines leading to underproduction
This can cause a pancytopenia
How does leukaemia present?
Think cytopenia-based symptoms e.g. anaemia, leucopenia and thrombocytopenia
Fatigue
Fever
Pallor
Petechiae
Abnormal bleeding
Lymphadenopathy
Hepatosplenomegaly
Failure to thrive (kids)
What causes petechiae and abnormal bruising?
Thrombocytopenia - petechiae
Reduced clotting factors - bruising
What are the different types of petechiae?
Petechiae
Less than 3mm
Burst capillaries
Purpura
3-10mm
Ecchymosis
> 1cm
What are the differentials for a non-blanching rash?
Leukaemia
Meningococcal sepsis
Vasculitis
HSP
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Traumatic or mechanical
Non-accidental injury
When is non-accidental injury considered as a differential for a non-blanching rash?
Children
Vulnerable adults
How is suspected leukaemia managed?
Suspected cancer
FBC within 48 hours
Children or young people with petechiae or hepatosplenomegaly sent for immediate specialist assessment
What investigations are used for leukaemia?
FBC - initial investigation
Blood film - abnormal cells and inclusions
LDH - Marker of increased cell turnover
Bone marrow biopsy - analyse cells to establish leukaemia
CT and PET scans - stage the condition
Lymph node biopsy - assess abnormal lymph node
Genetic tests - chromosome and DNA changes
Immunophenotyping - look for specific proteins on surface of cells to guide treatment and prognosis
Outline bone marrow biopsy
Taken from iliac crest
Requires local anaesthetic
Either aspiration or trephine
Bone marrow aspiration
Liquid sample of cells from bone marrow
Individual cell morphology
Bone marrow trephine
Solid core sample of bone marrow
Better assessment of cells and structure
Outline acute lymphoblastic leukaemia
Affects one of the lymphocyte precursor cells
Causes acute proliferation of a single type of lymphocyte usually B-lymphocytes excessive accumulation replaces other cell types in the bone marrow causing pancytopenia
Affects kids under 5 but also older adults
More common with Down’s Syndrome
Can be associated with Philadelphia chromosome (more associated with CML)
Outline chronic lymphocytic leukaemia
Slow proliferation of a single type of well-differentiated lymphocyte usually B-lymphocytes
Affects over 60s
Often asymptomatic but can present with infections, anaemia, bleeding and weight loss
Can cause a warm autoimmune haemolytic anaemia
Richter’s transformation - rare transformation of CLL into high-grade B-cell lymphoma
Smear or smudge cells - ruptured white blood cells that occur when preparing the blood film because they are aged or fragile
What happens in warm auto-immune haemolytic anaemia?
IgG antibodies mediate extravascular haemolysis
Normocytic anaemia
Occurs at room temperature
What investigation is used for warm AIHA?
Direct antiglobulin test
Confirms antibody-mediated destruction of RBCs
Asides from CLL what are the risk factors of warm AIHA?
SLE
Lymphoma
What is cold AIHA?
IgM autoantibodies activate complement system triggering RBC destruction in liver and spleen
0-10 degrees
What can cause cold AIHA?
CLL
Idiopathic
Mycoplasma pneumonia
Infectious mononucleosis
What do blood tests show in cold AIHA?
Raised reticulocyte count
Positive Coombs test
What is Richter’s transformation?
Development of aggressive lymphoma, usually DLBCL
How does Richter’s transformation present?
Rapid lymph node enlargement
B symptoms
Elevated LDH levels
Outline chronic myeloid leukaemia
Chronic phase
Accelerated phase
Blast phase
Chronic phase
Asymptomatic
Patients diagnosed after incidental finding of raised WCC, can last several years before progressing
Accerlated phase
Abnormal blast cells take up high proportion of bone marrow (10-20%)
Patients are symptomatic and develop anaemia, thrombocytopenia and immunodeficiency
Blast phase
Even higher proprtion of blast cells (20%) in blood
Severe symptoms and pancytopenia often fatal
Associated with the Philadelphia chromosome
What is the first line treatment in CML?
Imatinib
What is the Philadelphia chromosome?
Abnormal chromosome 22
Caused by reciprocal translocation between chromosome 9 and 22
Creates an abnormal gene sequence- BCR-ABL1
Codes for tyrosine kinase enzyme that drives proliferation of abnormal cells
Outline acute myeloid leukaemia
Many subtypes
Can present at any age but normally from middle age onwards
Can be due to transformation from a myeloproliferative disorder e.g. polycythaemia ruby vera or myelofibrosis
What is the most important prognostic factor for AML?
Cytogenetic type
What is associated with better prognosis in AML?
Hyperdiploidy
Extra chromosomes in blast cells compared to normal 46
What do blood films and bone marrow biopsy show in acute myeloid leukaemia?
High proportion of blast cells
Auer rods in cytoplasm of blast cells are characteristic of AML
What is the general management of leukaemia?
Oncology and haematology MDT
Treated with chemotherapy, targeted therapies and other
Targeted therapies
CLL mainly
- Tyrosine kinase inhibitors (ibrutinib)
- Monoclonal antibodies (rituximab, targets B-cells)
Radiotherapy
Bone marrow transplant
Surgery
What are the complications of chemotherapy?
Failure to treat cancer
Stunted growth and development in kids
Infections due to immunosuppression
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity
Tumour lysis syndrome
What is tumour lysis syndrome?
Release of chemicals when cells are destroyed by chemotherapy causing :
- High uric acid
- High potassium
- High phosphate
- Low calcium (due to high phosphate)
What does tumour lysis syndrome lead to?
Uric acid can form crystals in the interstitial space and tubules of kidneys causing AKI
Hyperkalaemia can cause cardiac arrhythmias
Release of cytokines can cause systemic inflammation
How is tumour lysis syndrome managed?
Very good hydration and urine output prior to chemo required in patients at risk of tumour lysis
Allopurinol and rasburicase both XOis which suppress uric acid
Low risk of TLS
Allopurinol
High risk of TLS
Rasburicase
Confirmed TLS
Rasburicase
Why is rasburicase better than allopurinol for higher risk TLS?
Coverts uric acid into allantoin which is more easily eliminated by the kidneys
