Table of Contents
- 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 serum free light chains 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
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: 2022/06/09 01:16 by gary1