Multiple Myeloma Flashcards
What is multiple myeloma?
A haematological cancer characterised by clonal proliferation of plasma cells in the BM, typically associated with a monoclonal component in the serum and/or urine (paraprotein, usually IgG or IgA)
→ osteolytic bone disease, anaemia, and renal failure
What is the CRAB of multiple myeloma?
- HyperCalcaemia - >2.75mmol/L
- Renal Impairment - Cr >177 or eGFR <40
- Anaemia - <100g/L drop of 20g/L; normochromic, normocytic
- Bone lesions - Lytic
What is the epidemiology of multiple myeloma?
- 2nd most common haematological cancer
- 67yrs median age
- M>F
- Black > caucasian
What is the aetiology of multiple myeloma?
Unknown
- ?Genetic inheritance
- ?Association to ionising radiation and petroleum products
What are the risk factors for multiple myeloma?
- MGUS
- abnormal free light-chain ratio (kappa/lambda ratio <0.26 or >1.65 is a powerful indicator for progression to MM)
- FH
- radiation
- petroleum
How does myeloma evolve?
Almost in all cases they evovle from an asymptomatic pre-malignant stage (MGUS - monoclonal gammopathy of undetermined significance0) at a rate of 1% per year.
In others there is an intermediate asymptomatic pre-malignant stage called “smouldering” myeloma. This progresses to myeloma at 10%/yr.
What is the protein which builds up in kidneys in multiple myeloma?
Bence Jones’ proteins
What are the symptoms of multiple myeloma?
- Bone pain - osteolytic lesions in back, ribs; fractures
- Anaemia- tiredness
- Hyperviscosity - bleeding, headaches, visual disturbance, bruisiing
- Infections
- Kidney failure - (due to Bence Jones’ protein precipitating in the renal tubules)
- Hypercalcaemia- thirst, nausea, constipation, mental change
- Dehydration (due to proximal tubule dysfunction from light-chain precipitation)
What are the diagnostic features of multiple myeloma?
Clonal BM plasma cells ≥10%, or biopsy-proven plasmacytoma + 1 or more of:
- Evidence of end-organ damage that can be attributed to:
- Hypercalcaemia: serum Ca >0.25 mmol/L (>1 mg/dL) higher than upper limit of normal or >2.75 mmol/L (>11 mg/dL)
- Renal insufficiency: Cr clearance <40 mL per minute or serum Cr >177 micromol/L (>2 mg/dL)
- Anaemia: Hb >20 g/L below lower limit of normal, or a Hb value <100 g/L
- Bone lesions on imaging
- Any one or more of the following biomarkers of malignancy:
- BM plasma cell percentage ≥60%
- Involved:uninvolved serum free light-chain ratio ≥100
- >1 focal lesion (each ≥5 mm) on MRI
What are the diagnostic features of smouldering myeloma?
- M protein (IgA or IgG) >30g/L in serum +/- BM plasma cells 10-60% +/- urinary paraprotein >500mg/24hrs AND
- No myeloma-defining events or amyloidosis
+ No CRAB features.
What are the diagnostic features of MGUS?
- M proteins <30g/L AND
- <10% plasma cells in BM
- Absence of CRAB (endo organ damage features)
(MGUS = monoclonal gammopathy of undetermined significance)
+No CRAB features.
What investigations would you do and what would you find?
- Immunoglobulin studies e.g. SPE, serum FLC levels, 24hr Bence Jones protein
- BM aspirate and biopsy - IHC for CD138
- FISH analysis - for high risk abnormalities
- Flow cytometry for immunophenotyping - diagnosis, minimal residual disease detection
Other:
- Urinalysis - Bence Jones proteins
- FBC - anaemia normocytic normochromic, thrombocytopenia, leukopenia
- U&E, creatinine - impaired renal function; Cr >176
- ESR - elevated
- Serum calcium - high
- Blood film - rouleaux formation with a bluish background
- CT/PET of symptomatic areas - ?lytic lesions
What do these show?
- Hb 93
- WCC 3.14
- Plt 87
- MCV 101
- Neut 1.6
- ESR12
No abnormal white cells on differential.
- Pancytopenia - all blood counts reduced
- MCV is elevated
- Normal/high ESR - partly due to reduced haemoglobin; but mostly due to increased protein in plasma (e.g.paraprotein in myeloma)
AML is unlikely as there are no abnormal white cells on differential.
When might you do a plasma exchange in myeloma?
Not commonly required but may have a role in patients with significantly impaired renal function at presentation.
Why might you get spinal compression in myeloma? What investigations would you do?
Vertebral damage due to myeloma–> plasmacytoma or vertebral collapse–> spinal cord compression
Investigations:
- skeletal survey - looks for othr areas of skeletal damage which might be osteoporotic or lytic in nature
- bone marrow aspiration - required to confirm myeloma diagnosis (excess of plasma cells)
- MRI scan of spine - degree of bone marrow infiltration
What are paraproteins?
IgA/IgG secreted by plasma cells which do not work as intended
What are the causes of myeloma kidney disease?
- Cast nephropathy - Light chains and Tamm Horsfall glycoproteins accumulate in proximal tubule forming casts. AL amyloidosis forms by misfolded lambda chains.
- Bence Jones proteins
- Hypercal
- Dehydration
Other: infection, drugs (loop diuretics, nephrotoxics)
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 macroglobulinaemia.
W = IgM producing cells MM = IgG/IgA producing cells
- If the patient has IgG/IgA MGUS what will they progress to?
- If the patient has IgM MGUS what will they progress to?
- MM
- Lymphoma
What is the WHO diagnostic criteria for MGUS?
- Serum M-protein <30g/L
- BM clonal plasma cells <10%
AND
- No lytic bone lesions
- No myeloma-related organ or tissue impairment
- No evidence of 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
