Haematology 11 - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance Flashcards
What immunoglobin is produced by myeloma cells?
One single type (eith IgG or IgA) which is known as paraprotein or M spike
What are Bence Jones proteins?
Urine monoclonal free light chains
What is Waldenstrom’s-Lymphoplacytic lymphoma?
A lymphoplasmocytic lymphoma with IgM paraprotein that causes visual disturbances
What is the name of the premalignant condition that always precedes myeloma?
Monoclonal gammaopathy of uncertain significance (MGUS)
What are the two most significant risk factors for myeloma?
Obesity
Black > causasians/ asians
What are the diagnostic criteria for MGUS?
Serum M-protein <30g/L
BM clonal plasma cells <10%
Asymptomatic
What is smouldering myeloma?
Serum M-protein >30g/L
BM clonal plasma cells >10%
Asymptomatic
What % of plasma cells is there in symptomatic multiple myeloma?
> 10%
What is the most notable interaction of myeloma cells with the bone marrow micro-environment?
Produce RANK ligand which stimulates osteoclasts to cause bone resorptions
What is the incidence of IgM myeloma?
Very rare (<1% of myelomas)
What does CRAB stand for in myeloma diagnosis?
Calcium (hypercalcaemia, >2.75)
Renal (creatinine >177/ eGFR <40)
Anaemia
Bone disease (see lytic lesions)
What is the most common and 2nd most common cytogenetic abnormality in myeloma?
- Hyperdiploid karyotype
2. IgH gene rearrangement
What are the 3 2014 Myeloma Defining Events
BM plasma cells >60%
involved:uninvolved FLC ratio >100
>1 focal lesion on MRI
Which part of the skeleton is affected by myeloma?
Proximal skeleton (spine, skull, knees)
Where are myeloma patients most likely to feel pain?
Back, chest wall, pelvis
What % of myeloma patients present with bone disease?
80%
What scan is necessary to detect bone lesions in myeloma?
Whole body CT is first line (X ray is obsolete for this use)
PET scan can also be used
Gold-standard = whole body diffusion-weighted MRI as this shows active vs treated disease (very expensive though)
What are the 2 most likely emergency presentations of myeloma?
Cord compression
Hypercalcaemia
What tests should be done to diagnose myeloma?
First: Serum protein electrophoresis Serum free light chains Next: Bone marrow aspirate and biopsy for immunohistochemistry FISH (for prognostic)
What is the best way to treat cord compression in myeloma?
Dexamethosone
Radiotherapy
What risk does myeloma present to the kidney?
Cast nephropathy - FLCs and Bence Jones proteinuria cause proximal tubule cell injury
How should myeloma kidney disease be treated in an emergency?
Bortezomib (proteasome inhibitor)-based therapy is the cornerstone of myeloma kidney disease treatment - once the patients can become independent from dialysis their outcomes improve dramatically
How does myeloma affect immunity?
Serum levels of normal Igs reduced
BM micro-environment interference also impairs myeloid, T and NK cells
Chemo also impairs immune response
What is tested for in BM biopsy in suspected myeloma?
Immunohistochemistry for CD138 - specific for myeloma cells in BM
What test can detect cytogenetic abnormalities of prognostic significance in myeloma?
FISH
What are the 3 parameters in the international staging system for myeloma?
Serum beta microglobulin
Cytogenetic risk
LDH
How does AL amyloidosis link to myeloma?
Misfolded FLCs aggregate into amyloid in target organs
How does amyloidosis affect the kidney?
Nephrotic syndrome
Give 5 features of the clinical presentation of AL amyloidodis?
Multiple myeloma
Nephrotic syndrome Unexplained heart failure Sensory neuropathy Abnormal liver function tests Macroglossia
What is MGRS?
Monoclonal gammaopathy of Renal significance
How is MGRS defined?
- One or more kidney lesions caused by mechanisms related to the produced monoclonal immunoglobulin (Ig)
- The underlying B cell clone does not cause tumor complications or meet current hematological criteria for immediate specific therapy
How do proteasome inhibitors work in multiple myeloma
Proteasomes are involved in removing misfolded proteins
If you prevent this, the amount of misfolded protein produced in myeloma will overwhelm the cell and cause apoptosis
Which monoclonal antibody is used in myeloma treatment?
Anti-CD38 (daratumumab)- anticd38 found on most plasma cells in MM
What is the difference between a pre-myeloma MGUS and pre-lymphoma MGUS?
Pre-myeloma: IgG/A-producing B cells
Pre-lymphoma: IgM-producing B cells
What are the 3 risk factors for MGUS progression?
- Non-IgG M spike
- M spike >15g/L
- Abnormal serum free light chain ratio
What are the clinical effects of myeloma due to?
- BM microenvironment interaction
2. Circulating paraprotein
What is the cause of dinovoangiogenesis in myeloma?
CD34 expression on myeloma cells promotes angiogenesis
What type of nephropathy does myeloma cause?
Cast nephropathy
What are the first investigations to be done in suspected myeloma?
Serum protein electrophoresis
Serum free light chains
What condition can produce MGUS/ myelomas part of its progression?
AL amyloidosis
Recall 6 options for myeloma therapy
- Alkylators (eg cyclophosphamide)
- Steroids (eg dex + pred)
- Thalidomide (new version used as thalidomide is highly toxic)
- Cereblon-binding drugs
- Proteosome inhibitors (bortezomib- used first line for MM renal disease)
- Anti-CD38 (daratumumab)- most effective
How do cereblon-binding drugs work?
Decrease levels of IRF4 –> decreased myc –> myeloma cell death
Myeloma cells HAVE a very well developed and extensive:
Endoplasmic reticulum
Is splenomegaly seen in MM?
No
Immunohistochemistry:
MM cells are positive for which 2 main markers:
Negative for which 2 main markers?
+ve: CD138 (diagnostic), CD38
-ve: CD19, CD20
