302 6. Haematology (the case of the man whose legs didn't work) Flashcards
What is multiple myeloma?
A type of bone marrow cancer
Characterised by:
Acute cord compression
Acute renal failure
Hypercalcaemia
Anaemia
How is multiple myeloma diagnosed?
By bone marrow biopsy showing:
Infiltration of plasma cells
Reduced normal haematopoiesis
What is myeloma?
Infiltration of malignant plasma cells in the bone marrow
Causes blood cells to become ‘sticky’, which can be measured with the erythrocyte sedimentation rate
Resultant “end-organ failure” (CRAB features)
What are CRAB features?
It’s a mnemonic aid covering four features that are associated with end-organ damage linked to myeloma progression
Stands for:
Calcium elevation
Renal insufficiency
Anaemia
Bone lesions
What are the symptoms of myeloma?
Symptoms of bone marrow failure:
Tiredness
Infections
Bruising
How is the kidney affected in multiple myeloma?
-Antibody blocks the kidney tubules
-Dehydration – often due to high calcium level
-Drugs – “non-steroidal” painkillers damage kidney
What tests results show the patient has myeloma?
Monoclonal immunoglobulin or paraprotein produced
Identified by protein electrophoresis of serum
Proteins can be separated by electric charge
Two main types: IgG and IgA
IgG has better prognosis than IgA
15% are light chain only:
kappa or lambda
What is the purpose of a light chain assay in diagnosing myeloma?
Measures free light chain assay in the serum
-Also known as “Bence Jones protein”
Measures free kappa and lambda light chains
-Myeloma causes skewing of the kappa/lambda 1:1 ratio
If there is an abnormal LC ratio > 10:1 then ?myeloma
-If >100:1 then high risk of renal failure
What investigations are done to diagnose myeloma?
Blood tests:
Haematology: anaemia, rouleaux, viscosity, ESR
Biochemistry: U+Es, LFTs, Ca/Ph, albumin, total protein, LDH, CRP, β2-microglobulin
Serum protein electrophoresis
Paraprotein (monoclonal M band, either IgG or IgA)
Other immunoglobulin levels typically low (immune paresis)
Serum free light chain assay
Abnormal κ/λ light chain ratio
Staging investigations
What is included in a Myeloma work-up?
Whole body MRI or CT scan for lytic lesions:
Urgent MRI scan of spine if suspected cord compression (?plasmacytoma)
May require urgent surgery or radiotherapy
If no end organ failure (CRAB symptoms) and plasma cells <10% in bone marrow, then diagnosis is MGUS (monoclonal gammopathy of uncertain significance)
Management is watch and wait
Bone marrow biopsy:
Plasma cells > 10% = myeloma
Smouldering myeloma if CRAB-ve
What is the treatment for myeloma?
-Chemotherapy for 4-6 months (cyclophosphamide, thalidomide, dexamethasone, bortezomib)
-Autologous stem cell transplant if young and fit
Name drugs used for treatment for myeloma
Old fashioned drugs for myeloma include:
-Steroids – usually dexamethasone
-Alkylators – usually cyclophosphamide
-Melphalan used in autologous stem cell transplant
Myeloma treatment has been revolutionised by targeted therapies:
-Thalidomide = immunomodulatory drug (but beware teratogenicity)
-Bortezomib = proteasome inhibitor (or Velcade, blocks the cell’s garbage can)
-Daratumumab = monoclonal antibody that targets CD38 on plasma cells
What are some haematological emergencies in myeloma?
Hypercalcaemia
-Consider myeloma
-Give iv pamidronate (bisphosphonate)
-Give iv fliuds +/- dexamethasone
Cord compression
-Consider if neurology (weak legs or cauda equina symptoms)
-Request urgent MRI imaging
-Surgical decompression or emergency radiotherapy
-Dexamethasone 8mg bd
