Haem: Multiple Myeloma Pt.2 Flashcards
How does multiple myeloma lead to lytic bone disease?
The myeloma cells release osteoclast activating factors and osteoblast inhibiting factors
How is bone imaging utilised in myeloma
- X-ray now obselete
- Whole body CT
- CT/PDG-PET
-
Whole body diffusion weighted MRI
- Bone marrow cellularity
- Active vs treated disease
How can multiple myeloma lead to paralysis?
Pathological fracture of a vertebra can lead to spinal cord compression.
Which imaging techniques are used to investigate multiple myeloma and what are their benefits?
- MRI - sensitive for bone marrow infiltration, expensive
- CT - sensitive for very small lytic lesions, high radiation dose
- PET scans - detects active disease, usually used with CT/MRI
Outline the mechanisms by which multiple myeloma causes kidney injury.
20-50% AKI at diagnosis
- Cast nephropathy - caused by high serum FLC, which is filtered and precipitates in tubules
- Hypercalcaemia - nephrocalcinosis
Normal amount of light chains in blood
20mg/dL
Multiple Myeloma diagnostic workup
Immunoglobulin studies
- Serum protein electrophoresis (M-spike)
- Involved:Uninvolved FLC ratio serum assay
- 24h urine Bence Jones protein
Bone Marrow aspirate/biopsy
- IHC for CD138
FISH
- For high risk mutations
Flow Cytometry
- Diagnostic
- Monitioring
Staging of Multiple Myeloma
How can myeloma cause AL amyloidosis
Light chains have the potential to misfold and deposit = Amyloid
(because of variable regions in immunoglobulin, can occur in MGUS or Smouldering)
Target organs:
Kidneys, Heart
others - GI, Skin, Liver, Spleen, Lymph
Stain for amyloid
Congo Red
Solid, non-branching and randomly arranged with diameter of 7-12nm
Common presentations of amyloidosis
- Nephrotic (70%)
- Proteinuria, Oedema
- Unexplained HF - (10%)
- Raised NT-pro-BNP
- Abnormal Echo and cardiac MRI
- Sensory Neuropathy
- Abnormal LFTs (9%)
- Macroglossia
- Malabsorption plus GI symptoms
What is MGRS
Monoclonal Gammopathy of Renal significance
Any B cell lymphoproliferation where there are:
- 1+ kidney lesions caused by mechanisms related to Ig produced and..
- Underlying B cell clone does not cause tumour complications or meet criteria for immediate specific therapy
What is the ideal treatment for MM
Autologous stem cell transplant
What are the four main types of drug treatment of multiple myeloma?
- Classical alkylator chemotherapy drugs (e.g. melphalan, cyclophosphamide)
- Steroids (very cytotoxic to lymphocytes)
- Immunomodulators (IMIDs e.g. thalidomide)
- Proteasome inhibitors e.g. bortezomib
Describe the physiological role of proteasomes.
- All proteins produced by a cell are folded in the endoplasmic reticulum
- If this process goes wrong, misfolded proteins would accumulate in the ER
- These misfolded proteins are insoluble and non-functional and lead to fatal ER stress and cell death
- So, we have proteasomes in the cytoplasm which targets misfolded proteins and degrades the into amino acids (a process called ER-associated degradation (ERAD))
- Inhibition of proteasomes leads to an accumultation of misolded proteins in myeloma cells leading to cell death
NOTE: proteasome inhibitors only work in multiple myeloma and not other cancers
Outline the 2 main treatment algorithms for MM
