HAEMATOLOGY - MYELOMA Flashcards
What is myeloma?
A cancer of plasma cells in the bone marrow
These plasma cells produce non-functional monoclonal paraprotein instead of immunoglobulins = overproduction of M protein
How common is multiple myeloma?
The second most common haematological cancer
What age does multiple myeloma usually affect?
Older people - about 70
What are the symptoms of multiple myeloma?
Bone pain; most commonly back pain
Recurrent infection
Anaemia symptoms
Renal failure symptoms
Symptoms of hypercalcaemia
Rarely, symptoms of hyperviscocity and bleeding due to thrombocytopenia
What causes the anaemia, neutropenia and thrombocytopenia seen in myeloma?
Bone marrow infiltration with plasma cells
Kidney failure also causes decreased EPO, decreasing RBC production
What causes recurrent infections in those with myeloma?
Paraprotein secretion means there’s a reduction in normal immunoglobulin levels
What causes renal impairment in myeloma?
Free light chain (paraprotein) secretion leads to deposition in renal tubules causing cast nephropathy
The hypercalcaemia, NSAID use can also contribute
What causes bone pain in myeloma?
Myeloma cells adhere to bone marrow stromal cells. Myeloma cells secrete IL-3 which inhibits osteoblast progenitor cell maturation, decreasing osteoblast activity. The cells also secrete DKK1 which inhibits OPG production by osteoblasts causing an increase in osteclastic activity. Myeloma cells also increase osteoclastic activity through MIP1 alpha and RANKL.
Increased osteoclastic activity without osteoblastic increase causes lytic lesions, usually seen in the spine, skull, long bones and ribs
What are the main antibodies associated with myeloma?
IgG and IgA
Why does myeloma cause hypercalcaemia?
Bone resorption
What symptoms can hypercalcaemia cause?
Nerve problems and dehydration
Whats it called when light chains are found in the urine of those with myeloma?
Bence jones proteins
How do you investigate myeloma?
Blood tests - anaemia, WCC, Plt, ESR high, increased paraprotein
Blood film - rouleaux formation because of paraprotein
U&Es for kidney function (increased urea, nitrogen and creatinine)
Serum calcium usually raised
Urine tests - bence jones proteins
Bone aspiration
Bone marrow biopsy - >10% plasma cell infiltrate
CT scan - lytic lesions
Free light chain ration >100
(>10% monoclonal plasma cell infiltrate with at least 1 of the four CRAB features; hyperCalcaemia, Renal impairment, Anaemia, Bone involvement)
How is myeloma treated?
Transfusions and EPO for anaemia
Hydration, bisphosphonates and high dose steroids for hypercalcaemia and kidney injury
Antibiotics for infections
Radiotherapy and systemic chemotherapy or high dose dexamethasone for bone pain Bisphosphanates can be given too
Preventing pathological fractures by pinning lytic lesions
Stem cell transplants
What proportion of cases of MGUS progress to multiple myeloma?
25%