Multiple Myeloma

  • malignant proliferation of plasma cells

  • multiple refers to many sites as imitates behaviour of B-cell

  • Characterised by paraprotein in serum

    • usually IgG or IgA, rarely IgD

  • Excretion of light chains, either kappa or lambda, in urine referred to as Bence-Jones protein

  • Median age at presentation 60 years

  • monoclonal immunoglobulin (paraprotein) secreted

  • kappa or lambda light chains can spill over into urine (Bence-Jones protein)

Characterised by

  • bone destruction

    • vertebral collapse

    • fractures

    • hypercalcaemia

  • bone marrow infiltration

    • anaemia
    • neutropenia
    • thrombocytopenia
    • paraprotein (occasionally causes hyperviscosity)

  • renal impairment

    • due to deposition of lightchains

    • hypercalcaemia

    • hyperuricaemia

    • amyloid (rare, after long time)

  • reduction in normal immunoglobulin → recurrent infections

Presentation

  • Bone Pain

  • Lassitude

  • Infection

Epidemiology

  • Incidence increases with increasing age

    • rare under 30, almost never in children

    • median age at presentation 65

History

  • Bone pain

  • Anaemia

  • Recurrent infections

  • Symptoms of renal failure

  • Symptoms of hypercalcaemia

  • hyperviscosity (rarely)

  • bleeding (rarely)

  • Bone pain and pathological fractures

    • plasma cells accumulate in bone marrow

    • form lytic lesions (painful)

  • Lassitude

    • prominent feature

    • may be only complaint

  • Metabolic features

  • Pancytopenia

    • anaemia

    • neutropenia

    • thrombocytopenia

  • Infections (presenting complaint in 10%)

    • due to reduced normal antibody and neutropenia

    • often Streptococcal pneumonia

  • Hyperviscosity (due to paraprotein)

    • visual disturbances

    • headaches

    • dizziness

    • heart failure

Examination

General

  • Pale

  • Tired

  • Unwell

  • May be in obvious pain

  • ? Dehydrated /?uraemic

  • Easy bruising

CVS

  • heart failure (v. rarely)

Respiratory

  • Pneumonia

Musculoskeletal

CNS

Investigations

  • FBC - normal or low

  • WCC - normal or low

  • Platelets - normal or low

  • ESR - almost always high

  • Blood film - may be rouleaux formation

  • U&E - evidence of renal failure

  • Serum calcium - normal or raised

  • Serum alkaline phosphatase - usually normal

  • Total protein - normal or raised

  • Serum albumin - normal or low

  • Protein electrophoresis - monoclonal band

  • Uric acid - normal or raised

  • Skeletal survey - lytic lesions

  • 24 hr urine - for light chain excretion

  • Bone Marrow aspirate

Diagnosis

  • 2 or more of

    • Serum electrophoresis

      • presence of paraprotein

      • commonest is IgG, then IgA, IgM, IgD

    • Urine

      • Bence-Jones proteins (not detected by Albustix)

    • Bone Marrow aspirate 

      • plasma cells(>10%)

    • skeletal bone survey

      • Lytic lesions 

Others

  • Full blood count

    • normochromic, normocytic anaemia

  • Blood film

    • rouleaux

  • Urea and electrolytes

    • may be signs of renal failure

  • ESR

    • raised (one of the few causes of ESR greater than 100mm/hr)

  • Serum calcium

    • raised

  • Serum alkaline phosphatase

    • normal (c.f. bony metastases)

  • Serum beta-2 microglobulin

    • guide to prognosis

Bone scan not helpful

Aetiological factors

  • ? Human Herpes virus 8 (HHV-8)

Treatment

  • melphalan or cyclophosphamide + prednisolone

  • correct anaemia, control infection

  • bisphosphonates to treat hypercalcaemia

  • Supportive

    • rehydration

    • treatment of hypercalcaemia

    • renal failure

    • antibiotics

    • transfusions of RBCs, platelets

  • Analgesia

  • Radiotherapy to painful bone lesions

  • Chemotherapy

    • melphalan in older patients

    • C-VAMP

  • ? Bone Marrow Transplantation

  • ? alpha-interferon

  • Plasmapheresis

    • to alleviate hyperviscosity

Prognosis

  • Median survival 3 years

Complications

  • Due to abnormal paraprotein

    • hyperviscosity

    • abnormal platelet function

    • renal damage

    • amyloid deposition

  • Due to infiltration of bone marrow

    • anaemia

    • leucopenia

    • thrombocytopenia

  • Suppression of normal immunoglobulin → poor humoral immunity

    • repeated infections

  • Skeletal destruction

    • pathological fracture

    • vertebral collapse

    • hypercalcaemia

    • pain

 

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