Multiple Myeloma and Principles of Autograft Flashcards
What are the risk factors for progression from MGUS?
M protein > 15g/L, non IgG MGUS, serum FLC ratio abnormal
What is the definition of MGUS?
M protein < 30 g/L
clonal plasma cells in BM < 10%
no myeloma defining events
What is the definition of smoldering myeloma?
M protein > 30g/L (serum) or > 500mg/24 hours (urine)
clonal plasma cells in BM 10% to 60%
no myeloma defining events
What is the definition of multiple myeloma?
clonal BM plasma cells > 10% or > 1 biopsy proven plasmacytoma AND 1 or more MM-defining events: > 1 CRAB feature > 1 biomarker of malignancy: clonal plasma cells in BM > 60% serum FLC ratio > 100 > 1 MRI focal lesion > 5mm on MRI
What are some of the common clinical presentations for multiple myeloma?
bone pain with negative bone scan low BMD with paraprotein normo/macrocytic anaemia with high total protein acute renal failure with anaemia back pain with anaemia hyperviscosity
What are the clinical features of hyperviscosity?
confusion, headache, visual changes, mucosal haemorrhage, high output heart failure
Which immunoglobulin is most likely to cause hyperviscosity?
IgM > IgA > IgG
What defines stage I multiple myeloma?
beta 2 microglobulin < 3.5
albumin > 35
no high risk cytogenetics
normal LDH
What defines stage II multiple myeloma?
beta 2 microgobulin between 3.5 and 5.5
What defines stage III multiple myeloma?
beta 2 microglobulin > 5.5
high risk cytogenetics or elevated LDH
What are the high risk cytogenetic features?
17p deletion translocation (14;16) translocation (16;20) translocation (4;14) 1q addition 1p deletion
What investigations are required for workup of a myeloma patient?
FBE and film UEC CMP SPEP, immunofixation quantification of serum Igs urinalysis, 24 hr UPEP and immunofixation BM aspirate and/or biopsy cytogenetics serum beta 2 microglobulin LDH serum free light chains
What are the findings of FBE, UEC, CMP, protein and albumin in multiple myeloma?
normocytic anaemia cytopaenias hypercalcaemia elevated creatinine elevated protein low albumin
What are the findings on a blood film in multiple myeloma?
rouleaux, circulating plasma cells
In what benign conditions may serum free light chain levels be elevated?
polyclonal hypergammaglobulinaemia
renal failure
however ratio will be normal -> ratio is only abnormal in monoclonal plasma cell disorder
What is the benefit of measuring the serum free light chain ratio?
can detect patients who are only producing a small amount of paraprotein
What percentage of patients with AL amyloidosis have an abnormal serum free light chain ratio?
98%
In what ways does multiple myeloma cause renal impairment?
myeloma cast nephropathy (most common) light chain deposition disease amyloidosis acquired fanconi hypercalcaemia hyperuricaemia
What is the pathophysiology of myeloma cast nephropathy?
paraproteins are filtered through the glomeruls
in the tubule they complex with tamm-horsfall proteins and form casts which block the tubules
endocystosed in the cell and cause a toxic inflammatory cascade (which relies heavily on NFkappaB)
What are the morphological features of a bone marrow aspirate in multiple myeloma?
dutcher bodies
flame cells
russel bodies
mott cells
What proteasome inhibitors are available in Australia for multiple myeloma treatment?
bortezomib
carfilzomib
What immunomodulators are available in Australia for multiple myeloma treatment?
thalidomide
lenalidomide
pomalidomide
What monoclonal antibody is available in Australia for multiple myeloma treatment?
daratumumab
What is the main side effect of bortezomib and thalidomide?
neuropathy
