Haem: Multiple Myeloma Flashcards
Another name for immunoglobulin
M spike
Paraprotein
Epidemiology of Multiple Myeloma
Black
Male
Older (eg. 67)
List some key features of multiple myeloma.
- Cancer of monoclonal plasma cells
- Abundance of monoclonal immunoglobulin
- Osteolytic bone lesions
- Anaemia
- Infections (due to deficient polyclonal response)
- Kidney failure (due to hypercalcaemia)
What is the pre-malignant condition for multiple myeloma?
Monoclonal gammopathy of uncertain significance (MGUS)
What is MGUS
Monoclonal Gammopathy of uncertain significance
Preceding Multiple Myeloma
Serum M <30g/L
Bone marrow cells <10%
Asymptomatic
No lytic lesions
No myeloma organ or tissue impairment
No evidence of B-cell proliferative disorder
IgA or G = Myeloma
IgM = Lymphoma
How common is multiple myeloma compared to other haematological malignancies?
2nd most common after B cell lymphoma
Risk stratification for Multiple myeloma
Mayo criteria
Based on 3 factors
- Isotype of immunoglobulin - IgG lower risk,
- M-spike >15g/L,
- Abnormal serum free light chain
What is smouldering syndrome
Both:
- Serum monoclonal protein (IgG or A) >30g/L or urinary ~500mg per 24h
or bone plasma 10-60% - Absence of myeloma defining events or amyloidosis
(no CRAB)
Spectrum
in between MGUS and Myeloma
What are the main mechanisms that drive plasma cell development?
- Class switch recombination
- Transcriptional control
What is another term of activated B cells?
Centroblasts
Outline the process by which B cells become plasma cells.
- Centroblasts mature in lymph nodes where they are stimulated by antigens and turn into memory B cells or immature plasmablasts
- Various transcription factors regulate the conversion of plasmablasts into plasma cells
Which components of the cell ultrastructure are particularly developed in plasma cells?
- Endoplasmic reticulum and golgi body
- This is where immunoglobulins are assembled, folded and modified before secretion
NOTE: plasma cells are the most secretory cells in the body (10,000 immunoglobulin per second)
Outline the pathogenesis of multiple myeloma.
- Errors occur in the genome of normal plasma cells (possible due to infection/inflammation)
- *most common - Hyperdiploid karyotype** (extra chromosomes)
- This leads to a limited monoclonal accumulation of plasma cells (MGUS)
- This is still harmless (5% of people >75 will have MGUS)
- 1% of people with MGUS per year will acquire more mutations that transform these pre-malignant cells into multiple myeloma cells
- This will trigger a cascade of events in the tumour microenvironment including increased angiogenesis and increased bone resorption
NOTE: it is difficult to develop targeted therapies for multiple myeloma because a lot of different mutations can cause it
What are the main clinical features of multiple myeloma?
- Calcium (high)
- Renal failure
- Anaemia
- Bone lesions (pain, pathological fractures)
- Monoclonal paraprotein
NOTE: patients with MGUS have no clinical features - there are some arbitary cut-offs for MGUS/multiple myeloma based on monoclonal serum protein, bone marrow plasma cells and annual risk of progression to multiple myeloma
What is the median survival for patients with multiple myeloma?
3-4 years