Malignancy in a child: Leukaemia Flashcards
Define acute lymphoblastic leukaemia.
Malignant clonal disease characterised by proliferation of early B- and T-lymphocyte progenitors.
Define acute myeloid leukaemia.
Malignant clonal disease characterised by a block in differentiation and unregulated proliferation of myeloid progenitor cells.
How is leukaemia typically recognised in a child?
Immature blasts >20% of BM cells
What are risk factors for leukaemia?
Triggers and causes usually unknown. May include ionising radiation, cytotxic drugs, benzene, Pre-leukaemic disorders (e.g. MPS and MPD), Down’s (particularly AML), neonates (30%) often develop transient abnormal myelopoiesis; resembles AML but resolves cspontaneously and completely after a few weeks.
What are risk factors for ALL?
Genetic lesions in the B- and T-lymphocyte progenitors. Karotype (80% are abnormal) important predictor of outcome. Suggestion of in utero origin of the leukaemic clone (cord blood studies). B-cell precursor ALL is the most frequent.
What are common cytogenetic abnormalities for ALL?
25% B-cell precursor ALL have the TEL-AML-1 fusion gene. t(12;21)(p13;q22). Both genes are required for haematopoiesis. TEL-AML-1 has been detected in cord blood. Philadelphia chromosome t(9;22)(q34;q11) is characteristic of chronic myeloid leukaemia (CML) but is a significant abnormality with ALL. 50% of T-cell ALL have activating mutations involving NOTCH1.
What are associations between inherited genetic syndromes and ALL?
5%
Trisomy 21, Fanconi anaemia, achondroplasia, ataxia telangiectasia, xeroderma pigmentosum, X-linked agammaglobulinaemia, high risk in siblings.
Summarise the epidemiology of ALL.
30/million/yr. Peaks 2–5 years old.
85% of childhood leukaemias.
What are general signs and symptoms of leukaemia?
Bone marrow function failure (anaemia, thrombocytopaenia (bleeding), neutropaenia (infection))
Organ infiltration: Hepatomegaly, splenomegaly, lymphadenopathy, bone pain, CNS, skin, gum hypertrophy
What are signs and symptoms of ALL?
Symptoms of bone marrow failure: Anaemia (fatigue, dyspnoea), bleeding (spontaneous bruising, bleeding gums and menorrhagia if adolescent) and infections (bacterial/viral/fungal).
Symptoms of organ infiltration: Meningeal involvement with headache, visual disturbance and nausea, cranial nerve palsies, retinal haemorrhage or papilloedema on fundoscopy, lymphadenopathy, tender bones, mediastinal compression in T-ALL with dyspnoea, hepatosplenomegaly, testicular swelling.
What are signs and symptoms of AML?
Bone marrow failure: Anaemia (lethargy, dyspnoea), bleeding (DIC or thrombocytopenia in case of M3 promyelocytic leukaemia), infections (bacterial/viral/fungal).
Tissue infiltration: Gum swelling/bleeding, CNS involvement (headaches, nausea, diplopia), bone pain.
Systemic: Malaise, weakness, pyrexia. Concurrent coagulopathy may be present (M3 and M5) leading to “d haemorrhage risk. Bone marrow failure: Pallor, cardiac flow murmur, ecchymoses and infection (pyrexia, mouth infections, e.g. Candida, herpes simplex, skin infections, e.g. Pseudomonas, respiratory, perianal infections, e.g. E. coli and Streptococcus faecalis, perineal infections).
Tissue infiltration: Skin rashes, gum hypertrophy, deposit of leukaemic blasts may rarely be seen in the eye (‘chloroma’), hepatosplenomegaly, adenopathy and lymphadenopathy.
What are appropriate investigations for ALL?
Bloods: Low Hb: normochromic, normocytic +/- low platelets, high WCC, high uric acid, high LDH, clotting.
Bone marrow aspirate/trephine biopsy: Hypercellular: >30% lymphoblasts, histochemical stains, flow cytometry, cytogenetics +/- specimen banking (if consented).
Cytogenetics: Karyotype abnormalities: chromosomal loss/gain, translocations. B-lineage ALL +ve with PAS stain, Tlineage ALL acid phosphatase.
Lumbar puncture: CSF analysis ?meningeal involvement.
Imaging (CXR): Mediastinal lymphadenopathy, thymic enlargement, lytic lesions.
Bone radiographs: ‘Punched-out’ lesions of the bones, e.g. skull, due to leukaemic infiltration.
What are appropriate investigations for AML?
Bloods: Low Hb, low Plts, low/high WCC, high uric acid, high LDH fibrinogen/D-dimers (if DIC is suspected in M3). Patients have a conserved clonotypic immunophenotype (‘molecular fingerprint’) that may be useful for disease monitoring.
Blood film: AML blasts show cytoplasmic granules or Auer rods.
Bone marrow aspirate/biopsy: Hypercellular with >30% blasts (immature cells). Histochemical stains, flow cytometry, cytogenetics ./specimen banking (if consented).
What is the management for ALL?
Chemotherapy:
- Remission induction: Chemo agents often given with steroids
- Consolidation: High dose multi-drug chemotherapy
- CNS treatment
- Maintenance: 2 years in girls and adults, 3 years in boys
- Consider allo-Stem Cell Transplant
Supportive: Blood products, ABx, Allopurinol, fluid, electrolytes - to prevent tumour lysis syndrome
What is the management for AML?
Chemotherapy
Similar principles to ALL but:
- No CNS prophylaxiss/maintenance therapy needed
- Consider allo-SCT in young
Specific: ATRA for M3 (acute promyelocytic leukaemia)
Supportive: Similar principles to ALL
Prognosis worse with age
