Myeloma and other plasma cell dyscrasia Flashcards
(21 cards)
What is myeloma? What is produced in myeloma?
Myeloma is a plasma cell malignancy in the bone marrow
♦ In myeloma monoclonal antibodies are produced – this means that each antibody is identical and comes from one particular B-cell lineage
=identical abody structure and specificy
(a monoclonal immunoglobulin is AKA paraprotein)
Paraproteins are a marker of underlying clonal B-cell disorder
‘rouleaux formation’
How are paraproteins detected?
serum electrophoresis: only one immunoglobulin will be shown to be being produced (this is seen as a distinct band)
normally the line would be hazy as lots of diff. abodies are being produced normally
How are paraproteins identified?
Can use serum immunofixation to classify the abnormal protein band
what are bence-jones proteins?
When immunoglobulins are synthesised in plasma cells, more light chains than heavy chains are produced and free light chains are secreted into the plasma along with intact immunoglobulin
-in a normal person this is 0.5g/day
If there is a polyclonal increase in the number of plasma cells (possibly due to an infection) or a monoclonal increase, due to a disease such as multiple myeloma, then the amount of free light chains in the plasma will increase and leak into urine– this is detected as bence-jones proteins.
Affects of myeloma: myeloma can affect the body due to direct tumour affect or because of paraprotein mediated affects. What are the direct tumour affects of myeloma?
Cause direct bone damage:
♣ bone lesions
♣ increased calcium
♣ bone pain
replace normal bone marrow = marrow failure
Affects of myeloma: myeloma can affect the body because of the direct tumour affect or because of paraprotein mediated affects. What are the paraprotein mediated affects of myeloma?
o Renal failure – light chain overproduction can cause renal failure
o Immune suppression
o Hyperviscosity
o Amyloid
Bone disease in myeloma: myeloma causes breakdown of bone by stimulating osteoclasts and inhibiting osteoblasts. How does this affect the: -skull -vertebra -systemic affects
Skull - pepper-pot skull
Vertebra - wedge fracture
systemic - hypercalcaemia: -Stones Bones Abdominal groans Psychiatric moans Thirst Dehydration Renal impairment
How does myeloma affect the kidney?
¥ 30% of patients have renal impairment at diagnosis
¥ Tubular cell damage by light chains - Light chain deposition; cast nephropathy (light chains normally can’t pass into kidney tubule but in excess they do and combine with tamm-horsfall protein and they aggregate here as insoluble casts = block nephron)
¥ Sepsis – from immunosuppression
¥ Hypercalcemia and dehydration
¥ Drugs; NSAIDs (take these due to bone pain but can push into renal failure)
¥ Amyloid
¥ Hyperuricaemia
¥ Renal damage may be reversible but may not be
What is the median age at diagnosis for myeloma? what is the survival?
ν Median age at diagnosis 65
ν Survival now 5-8 years for younger patients with more effective therapy
What are the 5 different treatments for myeloma?
ν Corticosteroids; dexamethasone or prednisolone - this kills plasma cells
ν Alkylating agents eg cyclophosphamide, melphalan
ν ‘Novel agents’ like thalidomide, bortezomib and lenalidomide - Many more becoming available even monoclonal antibodies against plasma cells!
(Monoclonal Abs target plasma cells = death)
ν High dose chemo/autologous stem cell transplant in fit patients
-harvest stem cells from pt and freeze them. Then use high dose chemo to destroy bone marrow – and myeloma cells. Then re-inject the pt. stem cells so that it takes less time to re-build the bone marrow back again
How is disease monitored in myeloma?
paraproteins level
What supportive treatment is there for myeloma? 4
¥ Opiate analgesia (avoid NSAIDs)
¥ Local radiotherapy - good for pain relief or spinal cord compression
¥ Bisphosphonates - corrects hypercalcaemia and bone pain
¥ Vertebroplasty – inject sterile cement into fractured bone to stabilise
What is monoclonal gammopathy of uncertain significance (MGUS)?
This is a benign condition caused by a small increase in plasma cells that replicate slowly and do not produce any clinical effect. 1% of these pt.s a year will get a second ‘hit’ (genetic mutation) and go on = myeloma – therefore monitor (but no treatment necessary)
(risk of progression to myeloma = 1% per year
in MGUS what is the paraprotein level, bone marrow plasma levels? is there evidence of myeloma end organ damage?
ν Paraprotein <30g/l ν Bone marrow plasma cells <10% ν No evidence of myeloma end organ damage; ¥ Normal calcium ¥ Normal renal function ¥ Normal Hb ¥ No lytic lesions ¥ No increase in infections
What is amyloid light chain amyloidosis? (AL amyloidosis) what does this lead to?
- progression
- prognosis
Rare disorder whereby there’s a small plasma cell clone with a mutation in the light chain: this causes light chains to be shaped in a certain way to ‘stick together’ and = insoluble beta pleated sheet which precipitates in tissues.
ν Accumulation in tissues causes organ damage
ν Slowly progressive
ν Multisystem disease
ν Different protein to SAA amyloidosis (chronic inflammation) and familial amyloidosis
ν Poor prognosis especially if cardiac amyloid
How are organs affected in AL amyloidosis?
Kidney - nephrotic syndrome Heart - cardiomyopathy Liver - organomegaly (deranged LFTs) Neuropathy - autonomic and peripheral GI tract - malabsorption
How is AL amyloidosis diagnosed?
Organ biopsy confirming AL amyloid deposition:
¥ Congo red stain – stains AL amyloid red
¥ apple-green birefringence is seen under polarized light
¥ Rectal or fat biopsy made be done if high clinical suspicion (less invasive)
Evidence of deposition in other organs:
¥ SAP scan (lights up areas of precipitation of amyloid)
¥ Echocardiogram
¥ Heavy proteinuria
What is waldernstrom’s macroglobulinaemia?
Clonal disorder of cells intermediate between a lymphocyte and plasma cell producing a characteristic IgM paraprotein
What does waldernstrom’s macroglobulinaemia cause?
Tumour effects:
- lymphadenopathy
- splenomegaly
- marrow failure
Paraprotein effects:
-hyperviscosity
-neuropathy
(the IgM paraprotein is v large and little light chains are produced so renal failure isnt a problem - it’s more the actual size of the protein making blood thicken)
What are the clinical features of waldernstrom’s macroglobulinaemia?
ν Hyperviscosity syndrome
ν Fatigue, visual disturbance, confusion, coma
ν Bleeding
ν Cardiac failure
ν B symptoms; lump, fever, night sweats, weight loss,
what is the treatment for waldernstrom’s macroglobulinaemia?
ν Chemotherapy – switches off production but takes time
ν Plasmapheresis (removes paraprotein from the circulation) – this is immediate
