Haematology 11 - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance Flashcards
What immunoglobin is produced by myeloma plasma cells?
One single type (either 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-Lymphoplasmocytic lymphoma?
A lymphoplasmocytic lymphoma with IgM paraprotein that causes visual disturbances
What is the name of the premalignant condition that always precedes myeloma?
Monoclonal gammopathy of uncertain significance (MGUS)
However, most individuals with MGUS will NOT develop myeloma
What are the two most significant risk factors for myeloma?
Obesity
Black > causasians/ asians
Also age - peaks between 84-85
What are the diagnostic criteria for MGUS?
Serum M-protein <30g/L
BM clonal plasma cells <10%
Asymptomatic (no lytic bone lesions, no myeloma-related organ damage)
No evidence of other B-cell proliferative disorder
What is smouldering myeloma?
Serum M-protein >30g/L
BM clonal plasma cells >10%
Asymptomatic
Essentially in between MGUS and symptomatic myeloma
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 primary cytogenetic abnormality in myeloma?
- Hyperdiploid karyotype
2. IgH gene rearrangement (t(11:14) IGH/CCND1)
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%
These are osteolytic lesions - never osteoblastic
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Whole body CT is first line (X ray is obsolete for this use)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
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?
Diagnosis and treatment within 24 hours, do MRI scan
Dexamethasone
Radiotherapy
What risk does myeloma present to the kidney?
Cast nephropathy - FLCs and Bence Jones proteinuria cause proximal tubule cell injury
Other contributing factors may include hypercalcaemia, use of diuretics, infections etc
How should myeloma kidney disease be treated?
TREAT AS AN EMERGENCY
Bortezomib-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 -> leads to chest infections and remarkably high levels of herpes zoster reactivation
Chemo also impairs immune response
What is tested for in BM biopsy in suspected myeloma?
Immunohistochemistry for CD138 - specific for myeloma cells in BM
