Myeloma and Plasma Cell Dyscrasias Flashcards
what is the role of the B cells
part of adaptive immune system:
- antibody production
- antigen presenting cells
what are immunoglobulins
antibodies produced by B cells and plasma cells
are proteins made up of 2 heavy and 2 light chains
each antibody recognises a specific antigen
what is the variable region of an immunoglobulin
the antigen binding site
how do B cells develop
initial production and development in the bone marrow (under influence of microenvironment)
Ig variable element generated (vjd segment)
self reactive cells removed
immature B cells with immunoglobulin (Ig) on their surface exit bone marrow
how do b cells circulate
travel to the follicle germinal centre of the lymph node
identify the antigen and improve the fit by somatic mutation or be deleted
may return to marrow as plasma cell or circulate as a memory cell
what is a plasma cell
short lived B cell that produces antibodies
what is the structure of a plasma cell
clock face nucleus open chromatin blue cytoplasm pale pale perinuclear area (golgi apparatus)
what causes a polyclonal increase in immunoglobulins
(produced by many different cell clones)
reactive to:
-infection
-autoimmune
-malignancy (reaction of host to malignant clone)
-liver disease
what is a monoclonal rise in immunoglobulin
all derived from clonal expansion of a single B cell
identical antibody structure and specificity
what is paraprotein
monoclonal immunoglobulin
what is paraprotein a marker of
underlying clonal B cell disorder
how can you detect immunoglobulins
serum electrophoresis (detects abnormal protein bands)
what does serum immunofixation do
classifies the abnormal protein bands
what is bence jones protein
immunoglobulin light chains, when excess leak into urine
detected by urine electrophoresis
what can cause an excess (>0.5g/day) of free light chain by normal plasma cells
anything that causes an increase in immunoglobulin synthesis (polyclonal: e.g. infection or monoclonal: e.g. multiple myeloma)
what causes paraproteinaemia
monoclonal gammopathy of unknown significance myeloma amyloidosis (AL) lymphoma chronic lymphocytic leukaemia
what is myeloma
plasma cell malignancy
what is MGUS
premalignant stage before asymptomatic myeloma
what is asymptomatic myeloma
when there is cancer but no organ damage
how does myeloma affect the body
clonal plasma cells:
- direct tumour cell effects
- paraprotein mediated effects
what are the direct tumour cell effects of myeloma
bone lesions
increased calcium
bone pain
replace normal bone marrow: marrow failure
what are the paraprotein mediated effects of myeloma
renal failure
immune suppression
hyperviscosity
amyloid
how is myeloma classified
by the type of antibody produced:
- IgG (59%)
- IgA (21%)
- bence jones myeloma (15%)
what does lytic bone disease look like
multiple punched out lytic lesions (myeloma)
wedge compression #s
what causes myeloma lytic bone disease
osteoblasts suppressed
osteoclasts activated
what are the features of hypercalcaemia
stones bones abdominal groans psychiatric moans thirst dehydration renal impairment
how does myeloma affect the kidney
light chains cause tubular damage light chain deposition: cast nephropathy (in thick ascending limb) sepsis hypercalcaemia and dehydration hyperuricaemia amyloid
what is the treatment for cast nephropathy
hydration
stop nephrotoxic drugs (NSAIDs)
switch off light chain production with steroids/ chemo
what is the treatment for myeloma
combination of chemo
corticosteroids
alkylating agents (e.g. cyclophosphamide)
novel agents (thalidomide)
HIGH DOSE CHEMO/ AUTOLOGOUS STEM CELL TRANSPLANT in fit patients
what is the median age of myeloma diagnosis
65
how do you monitor myelomas response to treatment
paraprotein levels
what is autologous haematopoietic stem cell transplant
administer re treatment to release stem cells from marrow into blood stream
collect the stem cells and freeze until needed
administer chemo
return thawed stem cells via transfusion
(way of delivering high dose chemo safely)
what is the prognosis for myeloma
5-10 years for younger patients
relapse is inevitable
what can be done for symptoms control in myeloma
opiate analgesia (avoid NSAIDs) local radiotherapy (pain relief/ spinal cord compression) bisphosphonates (corrects hypercalcaemia and bone pain) vertebroplasty (inject sterile cement into fractured bone to stabilise)
what is MGUS
when paraprotein <30 bone marrow plasma cells <10% no evidence of myeloma end organ damage: -normal calcium -normal renal function -normal Hb -no lytic lesions -no increase in infection
how many MGUS progress to myeloma
1% per year
what is AL amyloidosis
amyloid light chain amyloidosis
rare disorder where a small plasma cell clone has a mutation in the light chain= precipitates in tissues as an insoluble beta pleated sheet
how does AL amyloidosis present
organ damage
slowly progressive
what is SAA amyloidosis
caused by chronic inflammation
what is the treatment for AL amyloidosis
chemo (to switch of light chain supply)
what organs are damaged in AL amyloidosis
kidney (nephrotic syndrome) heart (cardiomyopathy) liver (organomegaly, deranged LFTs) neuropathy (autonomic, peripheral) GI tract (malabsorption)
how is amyloid diagnosed and staged
organ biopsy confirming AL amyloid deposition - congo red stain, rectal/ fat biopsy done if high clinical suspicion
to stage: look for evidence of deposition in other organs:
- SAP scan
- echo/ cardiac MRI
- nephrotic range proteinuria
what is used to monitor AL amyloid response to Tx
SAP scan- monitors disease burden and response
what is seen on congo red staining in AL amyloid
apple green birefringence under polarised light
what is waldenstroms macroglobulinaemia (IgM paraprotein)
lymphoplasmacytoid neoplasm (clonal disorder of cell inbetween a lymphocyte and plasma cell) IgM paraprotein
what are the effects of IgM paraprotein
tumour effects:
- lymphenopathy
- splenomegaly
- marrow failure
paraprotein effects:
- hyperviscosity
- neuropathy
what shape is the IgM antibody
pentameric
what are the clinical features of waldenstroms
hyperviscosity syndrome:
- fatigue visual disturbance, confusion, coma
- bleeding
- cardiac failure
b symptoms: night sweats, weight loss
what is the treatment for waldenstroms
chemo plasmapheresis (remove patient plasma (rich in IgM paraprotein) replace with donor plasma)
