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 as
1)
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:
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
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)
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
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
initial treatment of new diagnosis of multiple myeloma
transplant eligible, age < 66 years
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)