Leukaemia Flashcards
What is acute leukaemia?
aggressive disease in which malignant transformation occurs in a haemopoietic stem cell or early progenitor
- accumulation in bone marrow of early haemopoietic cells known as blast cells -> BM fail
When would you diagnose an acute leukaemia?
presence of atleast 20% of blast cells in BM or blood at clinical presentation
- lineage of blast cells defined with flow cytometry, morphology
- cytogenetic and molecular analysis essential and performed on marrow cells
What causes disease burden in acute myeloid leukaemia?
uncontrolled proliferation of immature, non-functional white blood cells ‘blasts’
- causes pancytopenia and haematopoiesis and presents that way
- blast cells enter blood stream and infiltrate other organs
What cells are involved in the myeloid lineage?
monocytes, granulocytes (eosinophil, basophil, neutrophil), erythrocytes, and platelets
What are the risk factors of AML?
- myelodysplastic syndrome and other pre-existing haematological disorders
- MDS, MPD, aplstic anaemia, paroxysmal nocturnal haemogloburia
- de-novo malignancy
- congenital disorders: Down’s syndrome, bloom syndrome
- environmental exposure: prior chemotherapy, radiation, tobacco smoke, benzene
- no identifiable cause: genetic alterations, isolated gene mutations
What are the clinical features of AML?
anaemia signs
thrombocytopenia - mucosal bleeding, easy bruising, petechiae, bleeding gums
neutropenia - infection
leukaemia infiltration
What clinical signs can be seen in AML?
- weight loss
- anaemia: pallor and cardiac flow murmur
- fever, pneumonia signs
- petechia, dermal bleeding and ecchymoses
- hepatosplenomegaly, lymphadenopathy and swollen gums
How would you investigate AML?
FBC - pancytopenia
peripheral blood smear - myeloblasts, auger rods
LDH - increased cell turnover
coagulation profile
BM biopsy
What diagnoses AML?
> 20% myeloid blasts in BM (or peripheral blood) or detecting cytogenetic abnormalities
How is AML managed?
- chemo: induction, consolidation, maintenance
- BM transplant
- Supportive therapy: blood transfusions, analgesia, abx, allopurinol, anti-emetics
What complications can be caused by AML ?
DIC
leukostasis
tumour lysis
What is acute lymphoblastic leukaemia?
most common childhood cancer with peak age 2-6 years
- arises from a clone of lymphoid progenitor cells
- buildup of these cells causes pancytopenia
*chromosomal translocations seen - t(12;21) most common and Philadelphia t(9;22)
What are some risk factors of ALL?
- Trisomy 21, Bloom syndrome, ataxia-telangiectasia
- pre-natal exposure to XR
- in-utero exposure to infection
- delayed post-natal exposure to infection
- environmental radiation
How might ALL present?
marrow failure
tissue infiltration - hepatosplenomegaly, bone pain, mediastinal mass, testicular enlargement
leucostasis
general B sx
How might you investigate ALL?
FBC - pancytopenia
hyperaemia, high LDH, hypercalcaemia
coagulation screen
bone marrow - 50 to 98% blasts
CSF
CXR
CT CAP
cytogenetics
What is the general mx of ALL?
pre-phase and supportive
induction chemo
maintenance therapy
stem cell transplant
palliative care
*more than 65 out of 100 people (more than 65%) will survive their leukaemia for 5 years or more after being diagnose
What are some complications of ALL?
tumour lysis
neutropenic sepsis
SVCO
chemo side effets
What is the pathophysiology of chronic myeloid leukaemia?
cancer of white blood cells specifically myeloid cells raised level of mature granulocytes (neutrophils, basophils and eosinophils), which then interfere with haematopoiesis
*philadephia chromosome - translocation of 9 and 22 activates a cascade of proteins that speeds up cell division and also inhibits DNA repair
What are the phases of CML?
chronic - 85%, asymptomatic, eventually will lead to accelerated
accelerated - significant progression and BM infiltration, splenomegaly and low cell counts
blast crisis - fever, fatigue, shortness of breath, abdominal pain, bone pain, enlarged spleen, chloroma
What are some risk factors for CML?
- radiation exposure - atomic bomb or nuclear reactor accidents
- increasing age
- males
What are some clinical features of CML?
*asymptomatic potentially
upper abdo pain
poor appetite
B sx
gout
infections
anaemia, thrombocytopenia sx
signs - pallor, hepatosplenomegaly, bruising
How might you investigate CML?
- FBC - leucocytosis, eosinophilia, basophilia, increased granulocytes, normocytic normochromic anaemia
- U&E
- LDH
- Urate
- peripheral blood film - all stages of granulocyte maturation, appearances similar to that of BM aspirate
- BM aspirate - to stage, cytogenetic sampling
How might CML be managed?
- tyrosine kinase inhibitors - targets BCR-ABL, inhibiting proliferation of malignant cells
- imatinib - first line
- aim to induce clinical, haemtological, cytogenic and molecular remission
- hydroxycabamide can also be used
- BM transplant in younger, possible cure
How might you define a blast crisis in CML?
final phase of evolution of CML and behaves like acute leukaemia, with rapid progression and short survival
- > 20%myeloblasts orlymphoblasts in the blood or bone marrow
- Large clusters of blasts in the bone marrow onbiopsy
- Development of achloroma(a solid focus ofleukaemiaoutside the bone marrow)
