Myeloma Flashcards
What is myeloma an example of?
Plasma cell dyscrasia
What are plasma cell dyscrasias?
Abnormal proliferation of a single clone of plasma or lymphoplasmacytic cells leading to secretion of immunoglobulin (Ig) or an Ig fragment causing the dysfunction of many organs (kidney)
Describe the classification of myeloma
Based on Ig product
Most (2/3) IgG
1/3 IgA
Very few are IgM or IgD
Describe why there is an increased susceptibility to infection in myeloma
Lack of other types of Ig
Immunoparesis
What are Bence jones proteins
Free Ig light chains of kappa and lambda type
Where are Bence jones proteins found?
In the urine as they are filtered by the kidney
What is the incidence of myeloma
5/100000
Which age is more affected by myeloma
70yrs
Which ethnicity has more myeloma
Afro-Caribbean
Which gender has more myeloma
Male
Give the clinical features of myeloma
Osteolytic bone lesions - cause backache, pathological fracture and vertebral collapse
Hypercalcaemia - may be symptomatic. Lesions due to increased osteoclast activity from signalling by myeloma cells
Anaemia, infection, thrombocytopenia - may result from marrow infiltration by plasma cells leading to symptoms of anaemia, infection and bleeding
Recurrent bacterial infections - due to Immunoparesis and also because of neutropenia due to the disease and from chemotherapy
Renal impairment - due to light chain deposition (up to 20% at diagnosis). The light chains have a toxic and inflammatory effect on the proximal tubule cells, but damage is mainly caused by precipitation of light chains in the loop of henle. Deposits can rarely be AL-amyloid (causing nephrotic syndrome). Monoclonal immunoglobulins also disrupt glomeruli.
What investigations would you do for myeloma and what may they show?
FBC - normocytic normochromic anaemia
Blood film - rouleaux
Persistently elevated ESR
Increased Ur and Cr
Increased calcium (in 40%)
ALP usually normal unless healing fracture
Bone marrow biopsy - many plasma cells with abnormal forms
Screening test - serum/urine electrophoresis - B2 macroglobulin is prognostic
Imaging - Xrays - lytic/punched out lesions
CT/MRI may be useful to detect lesions not seen on XR
List the diagnostic criteria of myeloma
Monoclonal protein band in serum or urine electrophoresis
Plasma cells on marrow biopsy
Evidence of end organ damage from myeloma - hypercalcaemia, renal insufficiency, anaemia
Bone lesions - a skeletal survey after diagnosis detects bone disease. Xrays of skull, spine, pelvis. Tc99m MIBI and PET
Describe the supportive management in myeloma
Analgesia for bone pain - avoid NSAIDs due to renal failure risk
Bisphosphonates - reduce fracture rates and bone pain
Local radiotherapy - can help in focal disease
Orthopaedic procedures - vertebroplasty or kyphoplasty may help in vertebral collapse
Anaemia corrected with transfusions and erythropoietin
Renal failure- rehydrate and ensure adequate fluids intake 3L/day to prevent further light chain induced renal impairment. Dialysis may be needed in AKI
Regular IVIG infusions may be needed if recurrent
Chemotherapy
Describe the use of chemotherapy in myeloma
Induction therapy with lenalidomide, bortezomib and dexamethasone
In suitably fit patients this may be followed by autologous stem cell transplantation
In those unsuitable for transplantation, induction therapy is typically continued for 12-18months or until serum paraprotein levels have plateaued. Treatment is typically held until paraprotein levels have started to rise again, at which point chemotherapy or stem cell transplantation may be considered
What type of drug is lenalidomide
Immunomodulator
List the SEs of lenalidomide
Teratogenic
VTE risk
Neutropenia risk
Give factors indicating a worse myeloma prognosis
> osteolytic lesions
B2 microglobulin >5.5mg/L
Hb <11g/L
Albumin <30g/L
What are the causes of death from myeloma
Infection
Renal failure
List the complications of myeloma
Hypercalcemia
Spinal cord compression
AKI
Hyper viscosity
What is paraproteinaemia
Presence of immunoglobulins produced from a single clone of plasma cells
What is the paraprotein recognised as on serum electrophoresis?
M band (monoclonal)
How many types of paraproteinaemia are there?
6
Name the 6 types of paraproteinaemia
Multiple myeloma
Waldenstrons macroglobulinaemia
Primary amyloidosis
Monoclonal gammopathy of uncertain significance
Paraproteinaemia in lymphoma or leukaemia
Heavy chain disease
Describe waldenstrons macroglobulinaemia
Lymphoplasmacytoid lymphoma producing a monoclonal IgM paraprotein
Hyper viscosity is common with ocular and CNS symptoms
Lymphadenopathy and splenomegaly also common
Increased ESR and IgM paraprotein on serum electrophoresis
Describe the treatment of waldenstons macroglobulinaemia
None if asymptomatic
Plasmapheresis for Hyperviscositiy
Chlorambucil, fludarabine or combination chemotherapy may be used
Describe monoclonal gammopathy of uncertain significance (MGUS)
Paraprotein in serum but no myeloma, primary amyloidosis, macroglobulinaemia or lymphoma, with no bon lesions, no bence jones proteins and a low concentration of paraprotein with <10% plasma cells in bone marrow. Some may develop myeloma/lymphoma so refer to haematology
Describe heavy chain disease
Neoplastic cells produce free Ig heavy chains, alpha chain disease is most important, causing malabsorption from infiltration of bowel wall (IPSID - Immunoproliferative small intestine disease)
May progress to lymphoma
