Leukaemia Flashcards
Define Leukaemia
Malignancy of the bone marrow and blood
Mutations in a single lymphoid or myeloid stem cell -> abnormalities in proliferation,
differentiation and cell survival of cell progeny -> expansion of leukaemic clone
Acute myeloid/myeloblastic leukaemia (AML)
Proliferation of immature myeloid stem cells (myeoblasts) in the bone marrow with spread
into the blood -> failure of normal erythrocyte, platelet, monocyte, neutrophil production
French-American-British classification (M0-M7)
• M3 – acute promyelocytic leukaemia (APML)
characterised by the presence of Auer rods
Chronic myeloid leukaemia (CML)
Reduced apoptosis and increased cell survival of myeloid stem cells -> progressive expansion
of leukaemic clone. Most cases are associated with chromosomal translocation t(9:22)
resulting in the BCR-ABL Philadelphia chromosome (↑ tyrosine kinase activity – treat
with imatinib). May later undergo blast formation -> AML or ALL
Acute lymphoblastic leukaemia (ALL)
Proliferation of immature lymphoblasts in the bone marrow with spread into the blood
Chronic lymphocytic leukaemia (CLL)
Failure of cell apoptosis -> progressive accumulation of functionally abnormal/incompetent
mature lymphocytes
Associated with BCL-2 (proto-oncogene) and p53 (tumour suppressor gene)
What are the causes/risk factors of leukaemia?
AML
• Radiation
• Benzene (smoking)
• Alkylating chemotherapy
CML
• Ionising radiation
ALL • Down’s syndrome (6x) • Chromosomal fragility • Radiation • Smoking • Viral infections (?trigger)
What are the symptoms of leukaemia?
AML Bone marrow failure • Anaemia (lethargy, dyspnoea, palpitations) • Bleeding • Opportunistic or recurrent infections Tissue infiltration • Gum swelling/bleeding • CNS involvement (headaches, nausea, diplopia)
CML Asymptomatic (40-50%) Hypermetabolic • Weight loss • Malaise • Sweating Bone marrow failure • Anaemia (lethargy, dyspnoea) • Easy bruising • Epistaxis Other • LUQ discomfort/fullness • Arthralgia/gout • Hyperviscosity (visual disturbances, headaches, priapism)
ALL Bone marrow failure • Anaemia (lethargy, dyspnoea, palpitations) • Bleeding (spontaneous bruising, bleeding gums, menorrhagia) • Opportunistic infections Organ infiltration • Tender bones • Meningeal involvement (headaches, nausea, visual disturbances) (*)
CLL Asymptomatic (40-50%) Hypermetabolic • Lethargy • Malaise • Night sweats Bone marrow failure • Anaemia (lethargy, dyspnoea) • Easy bruising • Epistaxis • Recurrent infections
What are the signs of leukaemia?
AML Bone marrow failure • Pallor • Cardiac murmur • Ecchymoses • Bleeding • Opportunistic or recurrent infections (fever, mouth ulcers, skin infections) Tissue infiltration • Skin rashes • Gum hypertrophy • Lymphadenopathy • Hepatosplen
CML Splenomegaly (90%) (*) Bone marrow failure • Pallor • Cardiac murmur • Ecchymoses • Bleeding NB: infections are rare in CML
ALL Bone marrow failure • Pallor • Ecchymoses • Bleeding • Infection (fever, GI, skin, resp) Organ infiltration • Lymphadenopathy • Thymic enlargement • Hepatosplenomegaly • Cranial nerve palsies • Retinal haemorrhage/papilloedema • Testicular swelling (*)
CLL Organ infiltration • Non-tender lymphadenopathy • Hepatomegaly • Splenomegaly Bone marrow failure (later signs) • Pallor • Cardiac murmur • Ecchymoses/purpura
What investigations are carried out for leukaemia?
AML
• FBC - macrocytic Anaemia, Leukocytosis with Neutropenia, Thrombocytopaenia.
• Blood Smear - the presence of blasts with Auer rods (crystals of coalesced granules).
- APML: Bi-lobed nuclei, hypergranulated blasts, and bundles of Auer rods.
• Clotting Screen - APTT, PT, TT, Fibrinogen and D-Dimers –important for DIC in APML.
• U&Es - degree of Urea elevation reflects the extent of tumour burden.
- Hypercalcaemia may be caused by bony infiltration or ectopic release of a PTHrP. Phosphorus may be elevated, with hyperkalaemia due to acute tumour lysis.
• Immunophenotyping -
blasts express surface antigens and molecular markers that help to identify their specific lineage –CD33 and CD34.
• Immunocytochemistry - myeloblast granules are +ve for Sudan black, chloroacetate esterase and myeloperoxidase;
- Monoblasts are +ve for non-specific and butyrateesterase.
• Bone Marrow Biopsy - hypercellular with >30 % blasts (immature cells).
• Cytogenetics - for diagnostic and prognostic information.
CML
• FBC - leukocytosis, with elevated neutrophils, basophils, and/or eosinophils.
• Anaemia
- Plt: Normal platelet count, Thrombocytosis (chronic or accelerated phases), or Thrombocytopenia (accelerated or blast crisis)
• U&Es - high potassium and urea
• Blood Smear -
A mixture of mature and immature myelocytes is pathognomic of CML.
• Bone Marrow Biopsy -
granulocytic hyperplasia, with raised myeloid–erythroid ratio.
• Cytogenetics - Philadelphia chromosome positive t(9;22)
qRT-PCR:
Detection of BCR-ABL fusion.
• Fluorescent in situ Hybridisation (FISH): if PCR not available.
ALL
• FBC - normocytic Normochromic Anaemia, leucocytosis/leukopenia, and/or thrombocytopenia.
• Blood Film - ymphoblasts evident on peripheral blood smear.
• Bone Marrow Biopsy - Hypercellular with > 30% lymphoblasts.
• Morphological Classification:
L1: Small lymphoblasts, scanty cytoplasm.
L2: Larger, heterogenous lymphoblasts.
L3: Large lymphoblasts with blue or vacuolated cytoplasm.
• Immunophenotyping - ALL blasts express surface antigens and molecular markers that help to identify their specific lineage e.g. CD20.
• Cytogenetics - Chromosomal abnormalities or translocations - Philadelphia Chromosome.
• Cytochemistry - B- and T-lineage cells show up with PAS stain and acid phosphatase, respectively.
• Lumbar Puncture - to monitor CNS involvement –may reveal leukaemic lymphoblasts
• CXR - may show mediastinal lymphadenopathy, thymic enlargement, lytic bone lesions.
• Bone Radiographs - mottled appearance with ‘punched-out’ lesions (e.g. skull caused by leukaemic infiltration).
CLL
• FBC - lymphocytosis (>5x109/L); Anaemia; Thrombocytopaenia.
Anaemia may be due to bone marrow infiltration, hypersplenism or autoimmune haemolysis.
• Blood Film - smudge/ Smear cells occur as a result of damage to lymphocytes during the slide preparation. If there is haemolysis, then schistocytes and polychromasia may be present. A mixture of mature and immature lymphocytes.
• Flow Cytometry - flow cytometry analysis of peripheral blood reveals cell surface markers typical for CLL, and diagnosis depends on detection of characteristic immunophenotypes.
- CD5, CD19, and CD23 positive.
• Bone Marrow Biopsy - Lymphocyticeplacement (25-95%) of normal marrow elements. Immunophenotyping shows the malignant cell to be a relatively mature B cell with weak surface expression of monoclonal IgM or IgD (kappa or lambda light chain only).
- ‘Hairy cell leukaemia’ is a low-grade CLL variant with good prognosis showing monoclonal proliferation of ‘hairy’ B-cells in blood, bone marrow and liver.
• CT - to assess organ involvement.
