Myeloma & Plasma Cell Dyscrasias Flashcards
Immunoglobulins contain 2 heavy & 2 light chains. What chain determines the type of antibody produced e.g. IgM or IgG
Heavy chain
Where do antigens bind on an antibody
The variable region (heavy & light chains)
List the 5 immunoglobulins and state whether they are monomers, dimers or pentamers
IgG, IgD, IgE - monomer
IgA - dimer
IgM - pentamer
Describe the basic structure of an immunoglobulin
Constant region
Variable region - 2x light & 2 x heavy chain (antigen binding site)
What process creates the variable (antigen binding site) of an immunoglobulin
VDJ region recombination
B cell receptor vs antibody
Ig on B cell surface - B cell receptor
Ig free in plasma - antibody
Briefly describe the process of plasma cell formation
Monoclonal vs polyclonal rise in immunoglobulins cause
Monoclonal - underlying clonal B cell or plasma cell disorder
Polyclonal - reactive change
What technique is used to detect immunoglobulins in the plasma
To test for presence of faulty Ig - Serum electrophoresis
To classify the faulty Ig (e.g. IgG) - Serum immune fixation
To quantify the amount of faulty Ig -
What is the name for a monoclonal immunoglobulin
Paraprotein
What are the 3 main causes of paraproteinaemia
MGUS
Myeloma
Amyloidosis
What is MGUS and what characterises it
Monoclonal gammopathy of undetermined significance
- monoclonal paraprotein in the serum or urine
- Paraprotein <30 g/l, bone marrow plasma cells <10%,
- No evidence of myeloma end organ damage
Why is MGUS clinically relevant
Is premalignant but increased risk of myeloma
What is myeloma
Cancer of a specific type of plasma cell
where there is agenetic mutation
causing it to rapidly and uncontrollably multiply
These plasma cells produce one type ofantibody
§(monoclonal paraprotein)
Summarise the effects of myeloma on the body
Bone disease
Bone marrow infiltration
Paraprotein secretion & amyloidosis
Myeloma renal disease
Describe the effects of myeloma on bone
Increased osteoclastic without increased osteoblastic activity
=> Lytic lesions
=> Fractures of long bone, vertebral collapse, hypercalcaemia
Describe the effects of paraprotein secretion
- Hyper-viscosity => confusion, headaches etc
- Reduced number of normal Ig => recurrent infections
- AL amyloidosis
- Renal failure
Describe the effects of myeloma renal disease
Deposition of light chains in tubules leads to cast nephropathy & renal impairment.
Renal impairment can be made worse by:
- Hypercalcaemia & dehydration (associated with myeloma)
- Use of NSAIDs
Summarise the clinical presentation of myeloma (think about the effects on the bone, bone marrow, kidneys)
General - weight loss, fatigue, weakness, lytic lesions
Bone - fractures, pain, vertebral collapse
Hypercalcaemia - Bones, stones, groans, moans, dehydration
Bone marrow infiltration - anaemia, infections, bleeding
Cast nephropathy - renal impairment
Paraprotein secretion - hyperviscosity S&Ss (rare)
Summarise the initial investigations for patients presenting with S&S of myeloma
- Bloods: FBC, U+Es, creatinine, calcium, CRP, PV
- Serumprotein electrophoresis: for type of paraprotein
- Plain x-ray: of symptomatic areas
How would you diagnose myeloma
- Bone marrow aspirate and trephine biopsy: with plasma cell phenotyping
- Immunofixation: of serum and urine to confirm and show the subtype of the paraprotein
How would you treat a patient with myeloma kidney disease
- Rehydration
- Stop nephrotoxic drugs
- Damage may be reversible
- Dialysis may be required
- Switch of light chain production (steroids/chemo)
How would you treat a patient with myeloma presenting acutely with bone disease & hypercalcaemia
- Hypercalcaemia - fluid and bisphosphonates
- Spinal cord compression - radiotherapy emergency
How would you treat a patient with hyper viscosity due to myeloma & paraproteinaemia
Plasmapheresis
Summarise the long term management of myeloma
First line
- Combination novel agent chemotherapy
- e.g. ‘novel agent’ with alkylating agent with steroids
If young & minimal comorbidities
- High does chemo &
- autologous stem cell transplant
Symptom control
- opiate analgesia or local radiotherapy (not NSAIDs) for pain
- bisphosphonates for hypercalcaemia & bone pain
- vertebroplasty to stabilise fractured bone
What analgesia would you want to avoid in myeloma
NSAIDs
What is waldenstroms macroglobulinaemia aka
Lymphoplasmacytoid neoplasm
- it is a clonal disorder of cells intermediate between a lymphocyte & plasma cell
Waldenstroms macroglobulinaemia shows clinical features of what two conditions
Lymphoma & myeloma
What paraprotein is characteristic of waldenstroms macroglobulinaemia
IgM
Clinical presentation of waldenstroms macroglobulinaemia
Tumour effects
- lymphadenopathy
- splenomegaly
- marrow failure
Paraprotein effects
- hyperviscosity (fatigue, confusion, coma, bleeding, cardiac)
- neuropathy (IgM binds to myelin-associated glycoprotein)
B symptoms
- fever
- night sweats
- weight loss
Waldenstroms macroglobulinaemia investigations
General
- Blood FBC & PV (marrow failure, hyperviscosity)
- CT imaging (lymphadenopathy, splenomegaly)
Macroglobulinaemia
- Serum protein electrophoresis &
- immunofixation (confirm IgM)
- densitometry (confirm mass)
Diagnosis
- Bone marrow biopsy (lymphoplasmacytes infiltration)
Waldenstroms macroglobulinaemia treatment
- Chemotherapy
- Plasmapheresis (removes paraprotein from the circulation)
