Malignant Haemopoietic Disorders

  • Malignant haemopoietic disorders include :
      Leukaemias
      Myeloproliferative disorders
      Myelodysplastic disorders
      Lymphoproliferative disorders
  • An uncontrolled proliferation of a clone of cells that have been derived from a mutant haemopoietic stem cell

    Clonal Expansion

    Figure 1. Clonal expansion of a neoplastic cell.
    There is a gap in normal development resulting in many blasts,
    some mature forms, but few intermediate stages of maturation.
    Eventually neoplastic cells spill over into the peripheral blood
    resulting in a leukocytosis.

  • These cells are often frozen in development and are usually not regulated by any CSF (colony stimulating factor) or inhibitors
  • These leukaemic cells keep dividing in the bone marrow as tumour cells usually having a much slower cell cycle (may take 7 days). Eventually, they displace normal haemopoietic cells frequently spilling into the peripheral circulation, invading organs including the spleen, lymph nodes (LN) and liver.
  • The number of blasts referred to, describes the conditions found within the bone marrow.

    Granulocyte Maturation Kinetics

    Figure 2. Schematic of the granulocyte reserves within the BM
    and throughout the peripheral cellular "pools".
    During a depleting event (eg. snake bite) the marginating
    pool is tapped, then the circulating pool, maturing
    pool etc. The BM compensates to maintain the total
    circulating cell number.

  • Share antigens with normal cells
  • Cytotoxic drugs, used to kill these cells will also affect normal cells as the biochemical cycles within both types of cells remain essentially the same.
  • Basohilia seen in CGL, MMM, Psy vera, ET
  • Eosinophilia seen in HL, CGL, MMM, Psy vera, ET
  • Panytopaenia seen in M3, M7, ALL, MM, HCL, MA

Classification

 

Clinical Classification

      Acute .Patient will die quickly (weeks-months) without treatment
      .Associated with very immature, undifferentiated cells, little mature and therefore normal function and some intermediate maturation
      .>30% blasts in the bone marrow
      Chronic .Without treatment it may be months or years before death
      .Mature and immature cells present
      .<30% blasts in the bone marrow
  • Acute leukaemia in kids is not as bad as chronic leukaemia in adults

Morphological Classification

      Myeloid .Derived from or resembling bone marrow
      .Acute Myeloid Leukaemia (AML)
      .Acute Myeloblastic Leukaemia
      .Acute non-Lymphoblastic Leukaemia (ANLL)
      .Chronic Myeloid Leukaemia (CML)
      .Chronic Granulocytic Leukaemia (CGL)
      Lymphoid .Acute Lymphoid Leukaemia (ALL)
      .Acute Lymphoblastic Leukaemia
      .Chronic Lymphoid Leukaemia
 

FAB Classification

  • French, American, British
  • Cytotoxic treatment disturbs normal and malignant cells-makes cell identification more difficult

Immunological Classification

MIC Classification

  • Morphology, Immunology, Cytogenetics

  • Certain age groups tend to suffer from, but are not restricted to, certain leukaemias
  • Treatment regimens are different for Myeloid compared to Lymphoid leukaemias

    Young Child (2-10yrs)
    (2.5-3.5/105 have/develop leukaemia)
    Adult
    (1/105@40yrs-1/106@70yrs
    ALL - 80% of leukaemias, most common blood/tissue malignancy in this group AML - 40% (most common transformation from myelodysplasia)
    AML - 20% of leukaemias ALL - 10-20%
    CML - Rare cases CGL - 20-25%
    CLL - Virtually unheard of in young children CLL - 25-30%

  • Despite some age trends, age should not influence the diagnosis
  • 50% of adult leukaemias are acute, and 50% chronic

Aetiology

  • Unknown, but certain associations/factors provide predispositions
  • Genetic:
      Down's syndrome has a greater than normal incidence
      Familial history - hereditary factors
  • Chemicals - eg. benzene
  • Chemotherapeutic drugs (can lead to secondary leukaemias)
  • Ovarian carcinoma
  • Hodgkin's disease treated cytotoxically
  • Viruses
      Animals - feline leukaemia virus
      Humans - HTLV I
  • Immunologic dysfunction
  • Somatic mutation
  • Radiation - dose and type dependent (high AML, but little CLL)
  • Environment - Clusters of cases associated with certain factors
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