Myeloma Flashcards
What is multiple myeloma?
Excess secretion of a monoclonal antibody - single clone of plasma cells undergone abnormal proliferation
Malignant disorder of plasma cells
What is the composition of antibodies?
Heavy chains - A,G,M,D,E
Light chains - Kappa, Lambda
Variable region
Two heavy and two light chains form a complete antibody
What is the pathophysiology of MM?
Development of MGUS
Premalignant plasma cell disorder leads to creation of plasma cell clone secreting monoclonal antibody
Progression from MGUS to MM - further cytogenetic abnormalities and changes to bone marrow microenvironment
Intermediate stage between the two is known as smouldering myeloma or asymptomatic myeloma
What is the clinical presentation of MM?
CRAB
Calcium levels high
Renal impairment - due to light chain nephropathy, light chain casts block tubes
Anaemia
Bone disease - lytic lesions, can lead to fractures
Medical emergencies - paraesthesia, fever, splenomegaly, hepatomegaly, lymphadenopathy
Hyperviscosity syndrome with high paraprotein levels
Spinal cord compression
What are the features of hyper viscosity syndrome?
Blurred vision
Headaches
Mucosal bleeding
Dyspnoea due to heart failure
Requires urgent plasma exchange
When should myeloma be suspected?
Have a low threshold
Close attention to those over 60 with:
Unexplained bone pain Pathological fractures Symptoms of hypercalcaemia Weight loss Symptoms of cord compression Symptoms of hyper viscosity Recurrent infections
How can we screen for myeloma?
Look for monoclonal antibodies
Protein electrophoresis - separates into bands showing which are normal, polyclonal or monoclonal
Immunofixation - fixes proteins in place using antibodies
Urine electrophoresis and serum free light chains
Looks at amount of light chain unbound to heavy chains in the blood
What is the diagnostic criteria for myeloma?
Identify monoclonal antibody, bone marrow analysis, assess organ damage
Monoclonal antibody detection - electrophoresis, serum free light chains
Bone marrow infiltration - use of aspirate and trephine with cytogenetics
Assess myeloma related organ damage - FBC, U&Es, bone profile, imaging, skeletal surgery
What are the features of MGUS?
Monoclonal protein low
Bone marrow plasma cells <10%
No organ damage
What are the principles of myeloma treatment?
incurable, treatment aims to increased periods of disease remission
Induction therapy - induce remission, VRd regime, use of steroids
ASCT - stem cells mobilised, harvested and stored after induction, then given high dose chemo, then reinfused
Maintenance - given post induction or post transplant
Relapse or refractory disease - ASCT, rechallenge or new therapy
What are some of the complications of treatment for myeloma?
Myeloma bone disease - bisphosphonates for boney pain Hypercalcaemia Cord compression Renal impairment Anaemia
Radiotherapy effects e.g. to breast area - risk of breast cancer in the future
Fertility if of child bearing age
What gene mutation allows cells to grow uncontrollably in Myeloma?
RAS gene
What do the monoclonal antibodies Bence Jones proteins cause in the kidneys?
They are usually reabsorbed in the PCT but large quantities means they precipitate out as casts
They cause tubular inflammation and destruction –> AKI –> decreased erythropoeitin –> anaemia
What causes AKI in myeloma?
Amyloid deposition
Tubular damage from bence jones protein
Hypercalcarmia leading to dehydration
What does increased osteolytic activity lead to?
calcium release –> hypercalcaemia –> dehydration, thirst, nausea, constipation
pathological fractures
lytic lesions (often vertebral) –> spinal cord compression
Bone pain
