multiple myeloma – clinical

what is polyclonal gammopathy in relation to multiple myelomas?
myelomas are overproductions of Ig, and when it is polyclonal, the gammopathy consists of a whole lot of Ig being produced by a diverse group of plasma cells at about equally high numbers
why is electrophoresis done during investigation of multiple myelomas?
this is done to separate the Igs into bands so that monoclonal spikes, polyclonal spikes or hypogammaglobulinemia can be determined. (these are within the gamma spike)
what is monoclonality? what can cause it?
this is a homogenous Ig population resulting from unregulated expansion of a B-cell population. it should be distinguishable from the backgroud population and causes myeloma, waldenstrom, B-cell lymphoma, primary amyloidosis, heavy chain disease, and light chain deposition disease
what do you do if you have a pt with a monoclonal spike (M-spike)?
you don’t know what is causing the spike, so you do immunoelectrophoresis/immunofixation
what is immunoelectrophoresis?
electrophoretic separation followed by immunoprecipitation (use of specific antibodies to human Ig). an “arc” will appear where the corresponding Ig is that is being produced
what is immunofixation?
strips soaked with anti-sera (radioactively tagged) are placed on agar. this works pretty much the same way as immunoelectrophoresis, but is more sensitive
why should both the serum and the urine be tested when checking for Ig?
some Ig only appear in the urine, such as the light chains
what does a urine SSA test for?
a urine SSA is a test for non-albumin in the urine. doctors will usually check for albumin w/a dipstick, but if that is negative and the SSA is positive, it means you have non-albumin protein in the urine
what is a 24 hr urine good for?
these do not need to be done anymore, but they are good for checking creatinine clearance (b/c myeloma can affect the kidneys)
if pts are having kidney failure as a result of MM, what do you treat?
the MM
what are the major criteria for MM? how many of these are needed for a dx?
plasmacytoma on bx, marrow plasmacytes >30%, or an M spike (IgA >2, IgG > 3.5, or bence jones 1 g/24 hrs). only 1 of these AND a minor is needed for a dx.
what are the minor criteria for MM?
marrow plasmacytes between 10 and 30%, M spike less than major criteria, lytic bone lesions, or decreased uninvolved Igs. only 3 of these is needed for a dx.
what is done after someone is diagnosed with MM?
staging. stage I: low M component, no signs of anemia, or hyperglycemia. stage II: (whatever isn’t I or III). stage III: anemia, hyperglycemia, bone lesions, and a high M component. A or B is then added to designate renal function: A is <2 creatinine (normal) and B is >2
what is MGUS? can this become MM?
a monoclonal gammopathy of undetermined significance. this consists of a stable M-spike, none or slight BJ proteins, and no bone lesions, anemia, hypercalcemia or renal insufficiency. 11% of people with this progress to MM
what is a smoldering myeloma?
a little more M spike than MGUS, but not enough to be MM. these have more than 10% plasmacytes, (but not the 30 required for MM). these pts do not have anemia, hypercalcemia or bone disease. they should be watched closely to see if they progress (which they probably will)
what is a solitary plasmacytoma?
a tumor of plasma cells within normal marrow, BUT no M spike in urine or serum, no anemia, hypercalcemia or low other Igs. radiation therapy will generally take care of it.
what is a plasma cell leukemia?
when plasma cells are seen in the peripheral blood in more than > 2×10^9.
what is a warning sign for primary care drs that the pt may have a MM?
if the globulin is increased and albumin is low
is bone fracture seen more often in MM pts?
what is a warning sign about possible MM to nephrologists?
kidney failure
even though MM is a lab diagnosis, what else still needs to be done?
a H&P
why should a CBC be done for MM pts?
you need to make sure that bone marrow function is still adequate not anemic/thrombocytopenic
why should a BUN/creatinine/electrolyte test be done for MM pts?
b/c MM affects the kidney, need to make sure they don’t go into kidney failure
why should a calcium/albumin test be done for MM pts?
to make sure they don’t have hypercalcemia b/c it can affect heart conduction and lower bowel motility
why should a skeletal survey be done for MM pts?
this is not a bone scan (which looks for blastic rather than lytic lesions), a skeletal survey x-rays being taken of all the bones in the body, head to feet
why should a unilateral bone marrow aspirate w/flow cytometry be done for MM pts?
this is to confirm the dx by plasma cells and look for lymphoma
why should a beta 2 microglobin test be done for MM pts?
the beta 2 microglobin is a marker of tumor burden and a better indicator of creatinine clearance than BUN
why can a cytogenetic/FISH test be done for MM pts?
to check genes for abnormalities
why should C reactive protein/LDH be done for MM pts?
marker for inflammation/tissue damage
what are occasional tests done for MM?
serum viscosity (blood may become viscous due the proteins in the blood), MRI/CT scan for solitary plasmacytoma and a fat pad bx for amyloid (w/congo red stain)
what is the treatment for a solitary plasmocytoma?
radiation therapy, which should fix it completely
what is the treatment for a smoldering or stage 1 myeloma?
watch and check labs every 3-6 mos
how are stage II and III pts treated?
aggressive chemotherapy if it can be tolerated.
can bone marrow transplants help with MM?
yes, esp autologous transplants which can put the pt in remission for 8-10 yrs
what are bisphosphonates?
these strengthen the bone and prevent further breakdown of bone/fractures. HOWEVER, kidney function needs to be watched with these – they are incompatible with bad kidneys
what are monthly labs for MM pts?
Ig, CBC, CMP, Ca++
what is done annually for MM pts?
bone scans (unless symptoms otherwise dictate), and stem cells if they can tolerate the necessary chemo
what is done with refractory MM?
autologus stem cell transplant, high does chemo, allogenic transplants, angiogenesis inhibitors
what are the steps of treating MM pts?
look for M spike, what type it is (IgG, etc), quantify it, stage them, look at clinical signs (hypercalcemia, bone lesions, etc)

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