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Myeloma (Diagnosis (FBC: raised ESR (with back pain indicate MM),…
Myeloma
Diagnosis
FBC: raised ESR (with back pain indicate MM), increased Ca, renal impairment, normochromic normocytic anaemia
Blood film - rouleaux formation and increased background staining
CXR, MRI, bone scan - bony disease e.g. pepper pot skill, hot spots in bone scan
Serum and urine electrophoresis - raised paraprotein - M band
Serum immunoglobulin -free light chain assay - kappa or lambda - free light chains are produced by almost all malignant plasma cells
Serum immunoglobulin - reduced which is called immunoparesis
Urine free light chains - Bence Jones protein
Bone marrow - plasma cell infiltration - varying degrees of maturity
Serum Albumin - low in advanced disease - renal impairment causes albumin to leak into the urine and excreted
Serum Beta 2 microglobulin - component of major histocompatibility complex (MHC) class I molecules (present on all nucleated cells so not on RBC - CD8 and cytotoxic T cells) - high levels as it is released by plasma cells
Clinical features
CRAB
C - hypercalcaemia
R - renal failure
A - anaemia
B - bone lesions
Useful in assessing treatment
Bone pain - back and chest - more advanced bone disease can lead to pathological fractures or vertebral collapse with loss of height
Anaemia - bone marrow infiltration by plasma cells
Infections - abnormal plasma cells not producing antibodies to fight infection and also normal WCC are crowded in the bone marrow
Renal failure and hypercalcaemia – polydipsia (excessive thirst), polyuria (abnormally large of dilute urine), anorexia, vomiting, constipation and mental disturbance
Amyloidosis (5%) - macroglossia, carpel tunnel, diarrhoea
Hyperviscosity syndrome - purpura, haemorrhages, visual failure, CNS symptoms, neuropathies and heart failure.
Pathology
1) Small number of plasma cells - MGUS - 50% have translocations involving the immunoglobulin heavy chain locus on chromosome 14q32
2) More genetic events causing progression to MM
3) Bone marrow change - induction of angiogenesis, suppression of cell mediated immunity and increased secretion of IL6. Causes bone lesions due to increase osteoclast activation
4) Myeloma cells secrete a monoclonal immunoglobulin or immunoglobulin fragments (M proteins or paraproteins) composed of single heavy chain and single light chain class, kappa or lambda. IgG (60%), IgA (20%) and light chain only in almost all the rest
Free light chain appearing in the urine is termed Bence Jones protein
Uncontrolled proliferation of clonal plasma cells in bone marrow that produce monoclonal antibodies/ paraproteins in serum and urine
It can never be IgM as this is a immature antibody. IgM is found in low grade lymphoma (Waldenstorms) and CLL
Other causes of increased paraprotein include: Plasmacytoma. MGUS, Waldenstorms macroglobulinaemia, CLL, Primary amyloidosis
Usually in patients >40 yeats
MM characterised by:
plasma cell accumulation in bone marrow
presence of monoclonal protein in serum/urine
symptomatic related to tissue or organ damage
Types
MGUS - Small number of plasma cells <10% and paraprotein <30 g/L. They have no clinical features. 1% per year progression
Smouldering - similar laboratory findings to MM but no organ or tissue damage causing clinical features i.e. asymptomatic. 10% per year progression
Symptomatic MM - >10% plasma cells, >30 g/L paraprotein, reduced normal Ig, abnormal light chain ratio, CRAB features
Plasmacytoma - myelomas do not have a
detectable M protein. It is localised tumour,
which has the absence of systemic myelomas
Management
Intensive therapy: Chemotherapy with stem cell transplant - VTD, VCD, VRD, CDT, RD
If unsuitable for intensive Tx, course of Melphalan + Prednisolone; this can control disease for ~1year, reducing bone lesions and paraprotein levels. Adding Bortezomib increases time to relapse, or Thalidomide improves event-free survival
Over time the disease is likely to relapse and progress, further chemotherapy, with the addition of radiotherapy to painful bone lesions can be required
Supportive
Renal: increase fluid
Bone disease: bisphosphonates
Compression paraplegia - surgical decompression laminectomy or irradiation
Anaemia: transfusion, Epo
Bleeding: repeated plasmapheresis (as it interferes with coagulation causing hyperviscosity syndrome)
Infection: rapid treatment, prophylactic infusion of immunoglobulin and oral ABx or anti fungal may be needed
Complications
Renal involvement
Malignant plasma cells produce cytokines that trigger expression of RANKL which activates osteoclasts. Causes hypercalcaemia. Kidney tries to filter out the calcium and there becomes deposits of calcium leading to kidney failure.
High calcium also causes renal stones to form that block the passage of urine from the kidneys to bladder = kidney failure
Urate levels are often high, which can lead to urate nephropathy. High urate levels in multiple myeloma can also cause gout. Allopurinol should be prescribed to reduce the level of uric acid which should prevent urate nephropathy.
MANAGEMENT: high fluid intake and bisphophonates
Amyloidosis
Extracellular deposition of protein in abnormal fibrullar form
Systemic amyloid light chain amyloidosis (AL amyloidosis) = most common in MM - monoclonal light chain deposition
Hyperviscotity syndrome
Relatively uncommon complication in multiple myeloma (2%)
Increase in blood viscosity due to an increased number of serum immunoglobulins
Prognosis
The combination of high beta 2 microglobulin and low albumin carry a particular poor prognosis
Low Hb, High Ca, High M protein or Bence Jones level, Multiple lytic lesion on X-ray, High creatine (i.e. renal failure), High B2 microglobulin, Low albumin, Poor response to chemo