The Acute Leukaemias Flashcards
(36 cards)
Define leukaemia
Leukaemia: malignancy arising from bone marrow stem cells. Leukaemic cells replace most of BM (crowding out normal haematopoiesis – bleeding, fatigue, infections), enter the peripheral blood and metastatise throughout the body
Auer rods?
In AML
Peroxidase positive
Risk factors for acute leukaemias
Genetic & environmental
Antineoplastic agents
Ionising radiation
Hodgkin’s lymphoma
Benzene
MM
Define acute leukaemia
Monoclonal disorders of early haematopoietic stem cells
Cells lose their ability to differentiate, but retain their ability to replicate
Defined as >20% blasts in the bone marrow
FBE in acute leukaemia
Normocytic or macrocytic anaemia (due to folate def)
Platelets < 100
WBC <10 - >100
Blasts - myeloblasts (more granules, auer rods), monoblasts (less granules, no auer rods), lymphoblasts
Bone marrow biopsy findings acute leukaemia
Hypercellular
Blasts > 20%
Usually completely replaced by blast cells
LAB tests for acute leukaemia
- Morphologic analysis
- Cytogenic studies (karyotype)
- Molecular markers
- Cell surface (CD) markers - flow cyto and immunophenotyping
- Cytochemical analysis (PAS, peroxidase, esterase, sudan black stains
Treatment of acute leukaemias
INDUCTION PHASE:
- Induce remission with high dose chemotherapy –> suppresses all clel lines –> patient prone to infections due to neutropenia
- Myeloid growth factors: reduces length of hospitalisations (by shortening neutropenic state) but do NOT increase survival
- Give RBCs and platelets
CONSOLIDATION PHASE (so the cancer doesn’t come back)
Once WCC normalise i.e. remission
- Consolidation therapy: prolongs remission, increases survival
- Sometimes can use gene expression profiling (DNA microarrays) to predict prognosis and guide therapy
Dangers of tumour lysis syndrome
- Cardiac arrhythmias (from electrolyte derangement) –> death
- Severe renal failure due to uric acid crystal deposition
Prevention of tumour lysis syndrome
Prophylactic allopurinol until neutrophils <0.5
Or if high risk, rasburicase instead
Continuous fluids (i.e. 8 hourly bags) with close monitoring of fluid balance
Treatment of florid TLS
3-5% will develop TLS despite appropriate prophylaxis
Renal POV:
- Continuous urine output recording
- Aggressive fluids, diuresis to wash out obstructing UA crystals
- Renal consult
- CRRT if required
Cardiac POV:
- ECG and cardiac monitoring
- Monitor electrolytes, cr, uric acid, LDH, every 4-6 hours
> treat hyperK, hypoC, hyperPhos
- Rasburicase (once only if used prophylactically, can have repeat doses if not)
-
What is the most common type of acute leukaemia?
AML
What diseases may progress to AML?
MDS, MPNs, PNH, aplastic anaemia, clonal haematopoiesis of indeterminate prognosis (CHIP), clonal cytopenia of unknown significance (CCUS)
What happens when a myeloid precursor cell becomes malignant?
Clones of abnormal cells that can proliferate, but cannot differentiate into mature blood cells or undergo apoptosis
Clinical features of AML (symptoms)
- Anaemia: SOB, weakness, dyspnoea
- TCP: bleeding/bruising
- Neutropenia: fever/infections
Headache/focal neurology due to CNS haemorrhage or leukaemic meningitis
Clinical features of AML (examination)
Pallor, bruising., bleeding
Occasionally splenomegaly/hepatomegaly or soft tissue mass (myeloid sarcoma). Lymphadenopathy is rare.
AML - blood results
- Low mature red cells, neutrophils and/or platelets
- May have leukocytosis (due to blasts)
- TLS features
- Other metabolic complications assoc with hyperleukocytosis and leukostasis
What is APML?
Acute promyelocytic leukaemia - distinctive syndrome that should be suspected in patients with: bleeding/bruising, TCP, leukaemia blasts with coarse cytoplasmic granules, low WCC, hypofibrinogenaemia and/or few circulating leukaemic cells.
It is a medical emergency that requires urgent management
What is the risk with APML?
DIC
Complications/emergencies with AML:
- Pancytopenia
- Hyperleukocytosis / leukostasis
- Metabolic abnormalities: TLS, renal failure
- Coagulation disorders: DIC from sepsis, drugs, AML or APML
- Involvement of CNS or eyes
What is hyperleukocytosis /leukostasis?
AML with myeloblasts >100,000/microL
Or myeloblasts >50,000/microL, with respiratory or neurological distress
Diagnosis of AML?
Bone marrow or peripheral blood blasts >20% with characteristic morphological, cytochemical, immunophenotypic and molecular features
Typical chromosomal / molecular abnormalities of AML
inv(16), t(16;16), t(8;21), t (15;17) or PML-RARA gene
DDc for cytopenias (aside from AML/ALL/CML)
In some cases, AML presents with cytopenias, with few circulating blasts.
DDx include: aplastic anaemia, myelofibrosis, MDS< medications, nutritional deficiencies, BM suppression (alcohol, infection), sequestration from organomegaly, autoimmune (felty), HLH
