Haematological Malignancies - Leukaemia Flashcards
What are multipotent stem cells
unspecialised cells that have 2 functions
- differentiation
- generation
they have the capacity to self renew through cell division
quiescent - long periods of inactivity
What is Leukaemia
Group of cancers of the blood/bone marrow characterised by abnormal proliferation of blood cells (usually WBCs)
What are the 4 different types of Leukaemia?
- Acute myeloid Leukaemia (AML)
- Chronic myeloid Leukaemia (CML)
- Acute lymphoblastic Leukaemia (ALL)
- Chronic lymphocytic Leukaemia (CLL)
What is Acute Leukaemia
Young immature blast cells in bone marrow/blood
more fulminant presentation and aggressive course
What is the pathology of Acute Leukaemia
- Failure to differentiate and mature into functional haematopoietic cells
- Uncontrolled proliferation of immature leukocytes
- Accumulation of abnormal large immature WBCs in the bone marrow
- Doubling time approx 2 weeks but can be as short as 4 days
Describe the stages of Acute myeloid Leukaemia
Stage 1 = normal RBCs, WBCs and platelets
Stage 2 = Symptoms - increase of immature leukocytes
Stage 3 = diagnosis - blast cells increasing
Stage 4 = worsening - few RBCs, WBCs and platelets, more blast cells
Stage 5a = anaemia - extreme fatigue, SOB, no functioning WBCs
Stage 5b = infection
What are the symptoms of Acute myeloid Leukaemia
Anaemia - decreased RBC, Hg, MCV = fatigue, pallor
Thrombocytopenia - decreased platelets = bruising, bleeding
Neutropenia - decreased neutrophils = infection
Others = bone pain, weight loss
What are the symptoms associated with organ infiltration
Lymphatic system - lymphadenopathy CNS involvement - confusion, seizures Skin/gum - gum hypertrophy Testicular Mediastinal mass - T lineage ALL
How would you diagnose Acute myeloid Leukaemia
Presence of pancytopenia (low RBCs, WBCs and platelets)
but increased WBCs of poorly differentiated blast cells
U&Es, LFTs
Imaging
Coagulation screen
Bone marrow aspiration /biopsy
What is the initial management of Acute myeloid Leukaemia
- Hydration and correction of electrolyte imbalance
- Treatment of infection
- Prevent uric acid nephropathy
- Correction of coagulopathy and blood product support
- Suppression of menses
- Birth control and fertility considerations (preserve eggs/sperm)
- psychosocial support
What is the treatment for Acute myeloid Leukaemia
Induction phase (4-6 weeks): intense chemotherapy to eradicate leukemic clone and induce complete remission Consolidation (4-12 weeks)/Intensification (8-12 weeks) further increase in dose to eradicate residual, undetectable leukemic clone prolonged maintenance phase (2-3 years) decrease the dose for outpatient treatment to prevent relapse
What supportive care strategies are there
- prevent tumour lysis syndrome
( high cell count diseases - as cell dies, content leaks into plasma leading to hyperkalaemia, hypercalcaemia, urate prescipitation in urinary tract and renal dysfunction)
pre-treat with aggressive hydration and allopurinol/Rasburicase - Prevent febrile neutropenia
with IV abx, antifungal, antivirals - prevent chemotherapy induced emesis (e.g., Metclopramide, Ondansetron)
- PCP prophylaxis (Co-trim)
- CSF
What are the poor prognostic indicators of Acute myeloid Leukaemia
- Unfavourable cytogenetics
- Older age
- Male
- High WBC count
- CNS disease
- Poor response to initial tx
What is aspariginase?
its used in consolidation/intensification
it catalyses hydrolysis of aspargine to aspartic acid and ammonia
this leads to a rapid depletion of aspargine which is an essential aa in lymphoid malignant cells for protein synthesis
results in considerable cytotxicity due to inhibition of protein synthesis
What to do if a pt experiences extramedullary relapse?
(It has a better prognosis than bone marrow relapse)
- Initiate localised therapy
- and 2nd full course of systemic chemotherapy
