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Acute Leukaemia – AML

  • Uncontrolled proliferation of hematopoietic precursor cells with loss of maturation and differentiation
    • The malignant cells (blasts) take over the BM and suppress normal haematopoiesis
  • Auer rods  – is characteristic of AML
    • Linear reddish cytoplasmic inclusions, diagnostic of myeloid lineage

Complications

  • Suppression of normal hematopoiesis
    • High risk of infection (granulocytopenia), and haemorrhage (thrombocytopenia)
  • Metabolic complications
    • Hyperuricemia, hyperphosphatemia, hyperkalemia – due to high cell turnover in malignant cells
    • Tumour lysis syndrome with ARF – due to urate crystals depositing in tubules (during chemo)
      • Allopurinol started and urine is alkalised prior to chemo to prevent this
  • Hyperleukocytosis and leukostasis syndrome
    • High blast count increases blood viscosity
    • Leukostasis syndrome (blasts >50,000/Μl) – altered mental status, respiratory failure, CHF
      • MC in AML
      • Leukapheresis (removal of WBCs) used to reduce blast count

Diagnosis

  • CBC and blood smear
  • BM aspirate/trephine biopsy
  • Cytochemical stains
    • MPO – positive in AML
    • Sudan black B – positive in AML
    • PAS – positive in some ALL
  • Flow cytometry
  • Cytogenetics

Complications of therapy

  • Chemo with cytotoxic agents causes BM aplasis which leads to cytopenias
  • Infections – E.coli, K.pneumoniae, Pseudomonas, S.aureus. Fungal infections. Viral (HSV, VZV, CMV)
  • Hemorrhage – due to thrombocytopenia. Prophylactic platelet transfusion given
  • Other SEs – N, V, alopecia, infertility
  • Cytosine arabinoside – cerebellar dysfunction
  • Anthracyclines (daunorubicin/doxorubicin) – cardiomyopathy
  • Therapy-related AML

ACUTE MYELOID LEUKEMIA

Pathophysiology and Classification

  • Very heterogeneous – can show differentiation along any lineages
  • De novo AML – in patients with no previous hx of hematologic disease
    • Patients trend to be younger, better survival
  • Secondary AML – in pts with preceding hematologic disease or who have receive chemo for another malignancy
    • In older patients, poorer prognosis
  • FAB  classification – based on morphology and cytochemical stains
    • Doesn’t include cytogenetic abnormalities, presence of dysplastic features or other prognostic factors
    • Criterion for AML dx is that ≥30% cells in BM/blood must be myeloblasts (in WHO it is lowered to 20%)
  • M2 t(8:21), M3 t(15:17), M4 t(16:16) are the most common categories
  • M3 shows distinct auer rods and M4 gum infiltration

Epidemiology

  • MC in older adults
  • Predisposing factors – Downs syndrome, Fanconi, ataxia-telangiectasia. Familial predisposition. Ionizing radiation. Benzene

Clinical features

  • Resembles the ALL symptoms of BM infiltration and suppression of normal haematopoiesis
  • Fever, mild splenomegaly
  • Tissue involvement (MC in AML than ALL)
    • Skin involvement – presents as violaceus non-tender plaques/nodules
    • Gum involvement – bleeding
  • Hyperleukocytosis with leukostasis – MC in AML than ALL
  • Metabolic – hyperuricemia, hyperphosphatemia, tumour lysis syndrome with ARF
    • Hypoglycemia – in patients with high blast counts (due to consumption of glucose by blasts)
  • DIC – MC in AML

Diagnosis

  • Anaemia and thrombocytopenia
  • Blood smear
    • Variable WCC – mostly increased, but can also be decreased
    • Blasts – larger and more variable than those in ALL
      • have more irregular nuclei
      • Can be impossible to distinguish from lymphoblasts
    • Auer rods – absolutely confirms myeloid lineage (see BM pic)
  • Bone marrow – hypercellular, with predominance of blasts/other immature cells
    • Stains – see table
  • Immunophenotype – flowcytometry most useful in distinguishing between AML and ALL
    • CD13, 15, 33 – Myeloid lineage-associated markers
    • CD7 – in M0, M1
    • Expression of HLA-DR – except on APL
    • CD19 – suggests t(8;21) translocation – ALL

Cytogenetics

  • Critical in diagnosis
  • M2 t(8:21), M3 t(15:17), M4 t(16:16)

Differential diagnosis

  • Reactive leukocytosis – has more mature cells than blasts
  • ALL
  • Myeloproliferative disorders (e.g. CML)
    • Have rarity of blasts in blood and BM
  • Myelodysplasia
    • <20% blasts = Myelodysplasia
    • >20% blasts = AML

Treatment

  • Divided into remission induction and postinduction phases
  • Remission induction
    • Anthracycline + ara-C
    • 3+7 regime – 3 daily doses of daunorubicin + 7 daily doses of ara-C
  • Postinduction therapy
    • Chemotherapy – high dose ara-C
    • BMT – most effective to decrease relapse (may be contraindicated in older patients due to transplant-related mortality)

Prognosis

  • Favourable – under 60s, t(8;21), (15;17). (16;16)
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