2.4 Acute Leukaemia Flashcards
Leukaemias are conditions characterised by a clonal increase in white blood cells in the peripheral blood or bone marrow:
Leukaemia:
- Increased white blood cells (cell line depends on type)
- In peripheral blood/bone marrow
Lymphoma
- Increased lymphocytes
- In ___________
Myeloma
- Increased _______
- In ____________
lymph nodes and other nodal tissues;
plasma cells;
various organs e.g. bones, kidneys
Acute leukaemia is defined by the ____________ (earliest morphologically recognisable white cells) in the bone marrow (>20%):
• Malignant blasts divide frequently → haematological and clinical state deteriorates very rapidly → medical emergency
• Patients can die without treatment, but may be cured with prompt and appropriate treatment → urgent diagnosis is essential (whether it is AML or ALL)
Acute myeloid leukaemia (AML)
- Occurs at any age (20% of children with leukaemia)
- Presents with predominantly _____
- Treatment: Require chemotherapy (different agents) → causes patient to feel unwell, lose hair and cause gut inflammation (with other complications)
Acute lymphoid leukaemia (ALL)
- Mainly occurs in children (80% of children with leukaemia)
- Presents with ________________
- Require chemotherapy (different agents) → causes patient to feel unwell, lose hair and cause gut inflammation (with other complications)
- Prolonged hospital stay (up to 6 months) for more prolonged treatment
- Maintenance treatment for ________
- CNS treatment
high percentage of blasts;
BM failure;
bone pain, lymphadenopathy, CNS and testicular involvement;
18 months
The clinical features of AML include bone marrow failure and local infiltration:
- BM failure (predominant)
• Anaemia (pallor, fatigue)
• Neutropenia (increased infection risk)
• Thrombocytopenia (increased bleeding risk) - Local infiltration
• Gum infiltration (if _____________)
• Lymphadenopathy (only occasionally in AML)
• Skin, CNS, spleen, liver, other sites (uncommon)
Complications
- Infections following neutropenia may be severe and life-threatening, which may be due to septic shock, ____________, and ___________________:
• __________________ is a variant of AML which presents with blasts with granular cytoplasm (appear like promyelocytes) → may lead to DIC without infection
- Very high white blood cell count leads to hyperviscosity and retinal haemorrhages and __________________
monocytic;
renal failure;
associated disseminated intravascular coagulation (DIC);
Acute promyelocytic leukaemia (APML);
retinal exudates.
[AML Diagnosis]
To determine whether the patient has ALL or AML, a bone marrow aspirate is taken from the __________ and the following investigations are performed:
Investigation
- Blood count and film BM morphology: Checking for _________ (representing coalescing granules)
• Indicates that the cell is in the _______________ rather than the lymphoid lineage
• Not possible to determine the lineage in absence of Auer rods
- Cytochemistry: Performed by staining BM histological slides with special stains (_____________ and ________ → myeloblasts):
• If cells are positive, they are likely to be myeloblasts
• Require high expertise → often unavailable at hospital laboratories - Immunophenotyping: Looks at the cell surface and cytoplasmic antigens (includes flow cytometry, immunocytochemistry and immunohistochemistry):
• Cell surface antigens can be detected by using visible antibodies to that antigen
• __________ is positive in acute leukaemias (early stem cells) - Cytogenetic analysis: Most AML patients have cytogenetic abnormalities → should be performed on all newly diagnosed patients (prognostic value + selection of appropriate treatment):
*AML M3m subtype: associated with the _____________ (exceptionally good outlook as long as the patient survives the initial few weeks → death from bleeding is major risk due to associated DIC which improves with treatment):
• Notable for blasts with many cytoplasmic Auer rods • Treatment: use of _______ (promotes differentiation)
iliac crest;
Auer rods;
granulocytic lineage;
myeloperoxidases; Sudan black;
CD34;
15;17 translocation;
retinoic acid
The treatment of AML includes the following measures:
Supportive care
• Red cell transfusion (for anaemia)
• Platelets (for thrombocytopenia)
• Antibiotics (for neutropenia)
• Central line administration of ____________ (compensate for RBC breakdown), and measures for fluid and electrolyte balance
Chemotherapy (e.g. daunorubicin, cytarabine)
• Works by damaging DNA → normal stem cells are often quiescent, and checkpoints allow for DNA repair
• Leukaemic cells are continuously dividing with lack of cell cycle checkpoint control → more susceptible to chemotherapy
• Combination of chemotherapeutic agents which work via different mechanisms of action (synergistic effect) with non-overlapping toxicity
allopurinol
ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL)
Acute lymphoblastic/lymphoid leukaemia (ALL) is the most common childhood malignancy, but is curable (85% of children with ALL are cured → accurate diagnosis is essential):
• Prognosis of ALL worsens with ________
Clinical features
- BM failure (predominant)
• Anaemia (pallor, fatigue)
• Neutropenia (increased infection risk)
• Thrombocytopenia (bruising and bleeding)
- Local infiltration (more dominant than in AML)
• Lymphadenopathy (± thymic enlargement)
• _____________
• Infiltration of testes, CNS, kidneys, other sites
• Bone pain
Pathological features Peripheral blood • Anaemia • Neutropenia • Thrombocytopenia • Lymphoblasts are usually seen
Bone marrow & other tissues
• Lymphoblastic infiltration (B or T-lineage*)
*B-lineage ALL starts in the __________, while T-lineage ALL starts in the _________ (may have thymic enlargement) → both display different genetic defects.
increasing age;
Hepatosplenomegaly;
bone marrow;
thymus
There is a high index of clinical suspicion of ALL if a child presents with profound BM failure, lymphadenopathy and CNS involvement:
• Blood count and film: shows ________ (confirms diagnosis) → bone marrow aspirate not necessary if there is high number of circulating blasts
• Immunophenotyping: confirms abnormal cellular type → clearer diagnosis
• Cytogenetic/molecular genetic analysis: subtyping of ALL + prognostic value • Other blood tests: blood group (e.g. for transfusion), LFTs, creatinine, electrolytes, calcium, phosphate, uric acid, coagulation screen
blasts;
There is a high index of clinical suspicion of ALL if a child presents with profound BM failure, lymphadenopathy and CNS involvement:
• Blood count and film: shows ________ (confirms diagnosis) → bone marrow aspirate not necessary if there is high number of circulating blasts
• _________________: confirms abnormal cellular type → clearer diagnosis
• Cytogenetic/molecular genetic analysis: subtyping of ALL + prognostic value
• Other blood tests: blood group (e.g. for transfusion), LFTs, creatinine, electrolytes, calcium, phosphate, uric acid, coagulation screen
blasts;
Immunophenotyping
T-lineage ALL (15%) and B-lineage ALL (85%) are treated differently, and must be tailored to the disorder and prognosis:
• Ph-positive patients with ALL require special treatment with _________ (targets specific genetic abnormality associated with the Ph chromosome)
• Treatment results in a 80% 5-year disease-free survival (for children) and 30 – 40% (for adults) → prognosis worsens with increasing age
• Important to know when to suspect acute leukaemia (for quick referral to haematologist) and to classify correctly (influences treatment):
o Highly toxic chemotherapy requires very good supportive care
o Many patients can be cured, and treatment results are still improving
Systemic chemotherapy + CNS-directed therapy: Given in different phases (induction cycle → ____________ → intensification → maintenance/continuation phase):
• Induction cycle: 1st cycle to induce remission
• Intensification/consolidation cycle: additional cycle when patient is in remission for ALL/AML (↓ blasts)
• *CNS-directed (for ALL): given into ____________ (spinal canal) via lumbar puncture for any CNS disease
• Prolonged continuation phase (18 months)
*Patients are treated for 2 years (girls) or 3 years (boys) → boys need longer to treat as the _______ must also be treated
Supportive care
- Blood products: Red blood cell and platelet transfusions
- Antibiotics: Broad spectrum antibiotics (if patient has fever) + prophylaxis for certain high risk infections (e.g. ____________)
- General medical care:
→ Central venous catheter
→ Hyperuricaemia: hydration, urine alkalinisation, allopurinol
→ Hyperphosphataemia: __________, calcium
→ Hyperkalaemia: fluids and diuretics
*Patients may require ___________________ before chemotherapy (if WBC count > 200 x 109/L)
imatinib
consolidation;
intrathecal space;
testes;
Pneumocystis jirovecii;
aluminium hydroxide;
haemodialysis and leukapheresis
