Leukaemia Notes

Leukaemia

Unregulated proliferation of a clone of immature blood cells

Aetiology

• Chromosomal abnormalities

  • Translocations

    • Philadelphia chromosome found in 95% of CML

    • Translocation between 9 + 22

    • Involves bcr-abl gene

• Predisposing factors

  • Radiation exposure

  • Previous chemotherapy (especially alkylating agents)

  • Exposure to benzenes

  • Down syndrome

Classification

Leukaemia

Acute Chronic

Myeloid Lymphoblastic Myeloid Lymphocytic

Acute Myeloid Leukaemia (AML)

Leukaemia arising from malignant transformation of myeloid precursor cells

(Neutrophils, basophils, eosinophils)

Epidemiology

• Increases with age

• Can be primary = spontaneous

• Or secondary = due to previous chemo/radiotherapy

Clinical features

• Huge variation

• Symptoms relate to

  • Infiltration of marrow with leukemic blast cells

    • Anaemia (lethargy, pallor, SOB)

    • Neutropenia (sepsis, recurrent infections)

    • Thrombocytopenia (bleeding, bruising)

  • Splenomegaly

  • Skin involvement – violaceous raised non-tender plaques

  • Hyperuricaemia due to high cell turnover = renal failure

Diagnosis

• Blood count

  • Raised WCC (as counts non-functioning WCC)

  • Low Hb

  • Low platelets

• Blast cells on film

• Auer rods on film

• BM aspirate and trephine (core biopsy)

  • Shows infiltration with leukemic blast cells

  • Sent to labs for

    • Cytochemistry (staining for cell type)

    • Immunophenotyping (looking for myeloid markers)

      • “Flow cytometry” – lyse other cells, process through machine, machine picks up CD antigens

    • Cytogenetics

Management

• Supportive care

  • Treat anaemia – RBC transfusion

  • Treat neutropenia – Broad spectrum abx IV when temp spikes

  • Treat thrombocytopenia – platelet infusion

• Chemotherapy

  • Aim = complete remission (<5% blast cells in BM)

  • 2 courses – induction and consolidation

• Stem cell transplant

  • Autologous – from self

    • Stem cells removed

    • Chemo to wipe out BM

    • Give back stem cells

  • Allogeneic

    • From HLA matched donor

    • Give chemo then donor stem cell

Acute Lymphoblastic Leukaemia (ALL)

= Clonal malignancy of lymphoid precursor cells

(B/T lymphocytes B>T)

Epidemiology

• Peak in incidence in childhood

• Prognosis better in childhood as cells more differentiated than in adult CLL

Clinical features

• Vary hugely

• BM infiltration causes

  • Anaemia

  • Neutropenia

  • Thrombocytopenia

• Other symptoms

  • Anorexia

  • Back/joint pain

  • Lymphadenopathy

  • Hepatosplenomegaly

  • CNS/testes involvement

Diagnosis

• Blood count

  • Raised WCC

  • Low platelets

  • Low Hb

• Blast cells on film

• BM aspirate and trephine

  • Shows infiltration with leukemic blast cells

  • Sent to labs for

    • Cytochemistry

    • Immunophenotyping

    • Cytogenetics (bcl-abl fusion gene)

Management

• Supportive care as for AML

• Chemotherapy

  • Induction + intensification + consolidation courses

  • Period of maintenance therapy e.g with methotrexate

• Can do allogeneic stem cell transplant

Prognosis

• Most important factor is age

• Initial response to treatment

Chronic Myeloid Leukemia (CML)

Clonal proliferation of myeloid precursor cells (neutrophils, basophils, eosinophils)

Chronic = abnormality further down the cell line therefore more differentiated cells

= More treatable

Pathogenesis

• Presence of Philadelphia chromosome (9:22 translocation forming bcr-abl gene)

  • Produces a protein that is thought to be ongogenic

Clinical features

• 3 distinct clinical phases

Primary = chronic phase – symptoms of anaemia, anorexia and weight loss

May have marked splenomegaly. Don’t usually...

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