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myeloma

multiple myeloma

introduction

  • multiple myeloma is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma.
  • It represents approximately 1% of all cancers and 2% of all cancer deaths.
  • the lifetime risk of getting MM in the USA is 1 in 161
  • peak age of onset is 65-70yrs but this appears to be falling as incidence increases and increasing cases are being diagnosed at age under 45 years (18% are younger than 50yrs, 3% are younger than 40 years)
  • MM is perhaps related to environmental toxins such as1)
    • firefighting (some first responders of 911 developed MM within 10 years)
    • hair dyes (> 20 years exposure)
    • farmers (insecticides, herbicides)
    • exposure to benzene and other organic solvents
  • African Americans and Native Pacific Islanders have double the incidence of Causasians and it is rare in Asians (< half the rate of Caucasians).
  • no clear hereditary component although recent studies suggest some familial clustering may occur. Mayo Clinic study found only 8 siblings of 440 MM patients developed MM.
  • 19% of patients with monoclonal gammopathy of unspecified significance (MGUS) develop MM within 2-19 years.
  • possible aetiologic role of herpes virus 8
  • myeloma arises from an asymptomatic premalignant proliferation of monoclonal plasma cells that are derived from post-germinal-centre B cells.
  • multistep genetic and microenvironmental changes lead to transformation of these cells into a malignant neoplasm
  • multiple myeloma patients have a proliferation of abnormal plasma cells which produce a monoclonal protein which is usually an immunoglobulin consisting of light and heavy polypeptide chains.
  • 75% of heavy chain cases produce IgG paraproteins, while the remaining 25% produce IgA paraproteins.
  • accumulation of plasma cells in the marrow may result in anaemia
  • the excessive production of immunoglobulin can be deposited in the kidney tubules reducing renal function and also causes a very high erythrocyte sedimentation rate (ESR) unless it is Bence-Jones myeloma.
  • diagnosis thus rests on:
    • Ix of immunoglobulins in blood and urine BUT detection of these alone is insufficient to confirm a diagnosis of myeloma.
    • plasma cells in bone marrow
  • 10-15% of patients have little or no skeletal, haematological or renal complications typical of clinically aggressive myeloma, and they have a relatively protracted, indolent course in the absence of Rx - these cases are designated smouldering or indolent myeloma
  • newer light chain assays can also detect the very rare non-secretory myeloma which has classical clinical and morphological features of myeloma but lacks a paraprotein or urinary Bence-Jones protein on electrophoresis.
  • POEMS syndrome
    • Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin changes
    • usually has an underlying osteosclerotic myeloma but may be assoc. with Castleman's disease

suspect myeloma if

  • anaemia with bone pain
  • vertebral crush fractures
  • unusually severe osteoporosis
  • susceptibility to recurrent bacterial infections
  • renal failure

monoclonal gammopathy of uncertain significance (MGUS)

  • a differential of myeloma
  • a clonal plasma cell or lymphoproliferative condition which usually runs a non-progressive, clinically benign course
  • relatively common with prevalence increasing with age - 3% of people aged 50-60yrs, 5% of people aged > 70yrs
  • occasionally may transform into clinically aggressive disease (1% per year)
    • transformation in a patient with IgM paraprotein is usually to a lymphoproliferative malignancy
    • transformation in a patient with IgG or IgA paraprotein is usually to myeloma.

initial screening investigations

protein electrophoresis of serum AND urine

  • can identify intact immunoglobulin or free light chains in ~98% of cases
  • intact monoclonal immunoglobulin migrates to a sharply defined band called “paraprotein” and is present in ~80% of patients with myeloma
    • it is almost always found in association with Bence-Jones protein in the urine protein electrophoretogram
      • Bence-Jones protein is a homogeneous kappa or lambda free light chain
  • in the remaining 20% of patients who do not have a paraprotein band on serum, monoclonal light chains can be detected on urine electrophoresis and this form of myeloma is called Bence-Jones myeloma.

further evaluation in the patient with paraprotein band on serum electrophoresis

paraprotein heavy chain Ig isotype

  • if it is IgM then the differential diagnoses to be considered here are monoclonal gammopathy of uncertain significance (MGUS) or lymphoid neoplasia such as a low grade non-Hodgkin's lymphoma such as Waldenstrom's macroglobulinaemia.
  • if it is IgG or IgA then differential diagnoses to be considered here is monoclonal gammopathy of uncertain significance (MGUS) or myeloma

further evaluation in the patient with Bence-Jones proteinuria OR IgG or IgA paraproteinaemia

  • multiple myeloma is confirmed by:
    • marked increase in bone marrow plasma cells
      • bone marrow biopsy may not be needed if typical features of monoclonal gammopathy of uncertain significance (MGUS) such as:
        • very low paraprotein concentration in patient with normal blood count, normal renal function and no skeletal survey abnormalities and no Bence-Jones protein in urine.
    • lytic or other characteristic bone lesions on X-ray - sleletal Xray survey is more specific than bone scan
    • also suggested by:
      • IgG paraprotein patients with > 30g/L IgG in serum
      • IgA paraprotein patients with > 20g/L IgA in serum
      • Bence-Jones patients with 1g of Bence-Jones protein per 24 hour urine collection
  • if the above do not confirm myeloma, then the diagnosis is likely to be monoclonal gammopathy of uncertain significance (MGUS)

initial treatment of new diagnosis of multiple myeloma

transplant eligible, age < 66 years

  • induction chemotherapy +/- salvage chemotherapy if poor response
  • then high dose melphalan with autologous stem cell transplant

transplant ineligible, age > 65 years

  • melphalan and prednisolone, or,
  • thalidomide plus melphalan and prednisolone
myeloma.txt · Last modified: 2016/04/23 14:01 (external edit)