HAEM: Multiple Myeloma Flashcards
What are the expansile tumours of MM called?
Plasmacytomas
What are the two types of abundant proteins in myeloma?
Bence jones = free light chains
Monoclonal IgA/G a.k.a. paraprotein/M spike
Compare MM and Waldenstrom’s.
W = IgM producing cells MM = IgG/IgA producing cells
What is the most common premalignant condition?
MGUS
If the patient has IgG/IgA MGUS what will they progress to?
Myeloma
If the patient has IgM MGUS what will they progress to?
Lymphoma
In MGUS definition:
a) What is the serum M protein level?
b) BM clonal plasma cell %?
a) <30g/L
b) <10%
What must be excluded in MGUS?
They must have no LYTIC BONE lesions, no MM-type organ/tissue damage, no other B-CELL proliferative disorder
What criteria stratifies risk to MM progression in MGUS?
Mayo criteria - looks at non-IgG spike, if M-spike >15g/L and at SFLC ratio
What are the two main criteria which define smouldering MM?
a). M protein >30g/L (or urinary 0.5g/day)
+/- BM plasma cells 10-60%
b) No amyloidosis and no MM defining events
What criteria stratifies risk to MM progression in smouldering MM?
IMWG 2019 (if everything >20 incl SFLC ratio then poor prognosis)
List the stages of progression of myeloma.
MGUS - PC <10%, M <30g/L Smouldering - PC>10%, M >30g/L Symptomatic MM* Remitting relapsing MM Refractory Plasma cell leukaemia
- > 10% or plasmacytoma + urine/serum paraprotein+ symptoms after this stage
What is the most common primary genetic event in MM? What about secondary?
1o = Hyperploidy 2o = copy number abnormalities, hypomethylation, mutations
What is the CRAB criteria for MM?
CRAB Calcium >2.75mmol/L Renal Cr>177 or eGFR <40 Anaemia <100g/L or -20 Bone disease - lytic
What are the myeloma defining events i.e. numbers/%?
a) PC >60%
b) SFLC ratio >100 (invovled:uninvolved)
c) >1 focal bone lesion on MRI (>5mm)
What are the two main emergencies in MM?
Cord compression and hypercalcaemia
What are the causes of myeloma kidney disease?
Cast nephropathy Bence Jones proteins Hypercal Dehydration Other: infection, drugs (loop diuretics, nephrotoxics)
How do casts form in MM kidney disease? How does AL amyloidosis form?
Light chains and Tamm Horsfall glycoproteins accumulate in proximal tubule forming casts
AL - misfolded free light (LAMBDA in most) chains aggregate in target organs
What biologic is the main used in MM kidney disease?
Bortezomib
Which CD antigen should be tested for in MM?
CD138 with immunohistochemistry
Name a high risk mutation in MM.
del(17q)
t(4;14) IGH/FGFR3
t(14;16) - IGH/MAF
Is amount or amyloidogenic potential of free light chains more important for AL amyloid development?
potential
Name the light chains most commonly implicated in renal and cardiac AL amyloid.
Lambda chain
Renal - IGLV 6-57
Cardiac - IGLV 1-44
What are the complications of AL amyloidosis?
NephrOtic syndrome –> proteinuria (not BJP)
etc
