multiple myeloma
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Multiple Myeloma
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• What is multiple myeloma?
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• It is a malignant disease of the plasma cells of bone marrow.
• Remains an incurable disease.
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• What is the most common monoclonal protein found in MM?
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• IgG (55%)• IgA (20%)
• In approximately 20% there is no paraproteinaemia, only light chains in the urine.(BJP)
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• What are the risk factors for MM?
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• Age >60.• Exposure to pesticides.• Radiation• Benzene• ? Presence of IL-6 and HHV8 (Kaposi’s
sarcoma Herpes Virus)
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• What are the clinical features of MM?
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• Disease of elderly.• Median age >60• More common in black Africans.
• Bone destruction• Renal failure• Bone marrow infiltration
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• May be symptomatic or asymptomatic.
• Symptomatic myeloma characterized by presence of ROTI and CRAB.
• Myeloma Related Organ or Tissue Impairment.
• Calcium levels increased• Renal failure• Anemia• Bone lesion
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• What is the cause for renal failure in MM?
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• Deposition of light chains in the tubules (most common).
Also:• hypercalcaemia, hyperuricaemia, use of
NSAIDs (rarely) and deposition of amyloid.
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• What is the consequence of bone marrow infiltration with plasma cells?
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• anaemia• neutropenia• Thrombocytopenia• Production of paraproteins.
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• What is the consequence of bone destruction in MM?
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• Fracture of long bones• Vertebral collapse• Hypercalcemia
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• What is the cause of spinal cord compression in MM?
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• Due to soft tissue plasmacytomas
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• In terms of cytogenetics which one has a better prognosis?
• Hypodiploidy (<45 chromosomes) or• Hyperdiploidy (>50 chromosomes)?
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• Hyperdiploidy.
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• In MM which bone activity is increased?• Osteoblast or osteoclast?
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• Increased osteoclastic activity.
• That is why biphosphonates is useful in MM because it inhibits osteoclastic activity.
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• Why do patients with MM get recurrent infections?
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• Because there is a reduction in the normal immunoglobulin levels (immuneparesis), contributing to the tendency for patients with myeloma to have recurrent infections.
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What are the lab findings in MM?
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• FBC- normal or low.• ESR, CRP-almost always raised.• Blood film- Rouleaux formation, macrocytosis.• U&Es, Cr-renal failure• Serum B2 microglobulin >2.5mg/L.• Raised LDH• Serum calcium- normal or raised.• Serum ALP-normal• Total protein-normal or raised.• Serum albumin- normal or low.• SPE- monoclonal band.• Serum free light chain assay• Uric acid-normal or raised• 24-hour urine electrophoresis and immunofixation is used for
assessment of light-chain excretion.• Bone marrow aspirate or trephine shows characteristic infiltration by
plasma cells .Amyloid may be found.
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• What are the imaging studies used to diagnose MM?
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• Skeletal survey-lytic lesion. easily seen in skull.• CT, MRI and PET are used in plasmacytomas
(bone or soft tissue deposits).• Sestamibi- picks up bone dx missed on skeletal
survey.• MRI spine- may show imminent
compression/collapse.
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• Myeloma affecting the skull. Note the rounded lytic translucencies produced by infiltration of the skull with myeloma cells.
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• What are the stages of MM?
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• How do you diagnose MM?
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Two out of three diagnostic features should be present:
• paraproteinaemia or Bence Jones protein• radiological evidence of lytic bone lesions• an increase in bone marrow plasma cells.
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• What is the treatment for MM?
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• supportive care • chemotherapy • Autologous or allogeneic stem cell
transplantation.
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• What is the supportive therapy?
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• Treat the anemia-erythropoetin helps.• Treat the infection• Radiotherapy/sytemic chemo/high dose dex
for bone pain.• Kyphoplasty and vertebroplasty for treating
vertebral fractures.• Biphosphonates (pamidronate/zoledronic
acid)- beware of osteonecrosis of the jaw.
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• What are the chemo options?• For Elderly?• For Younger patients?
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For elderly
• If not fit for transplant, treat with Melphalan + Prednisone + Thalidomide (MPT).
Beware: • Melphalan +prednisone = stem cell toxicity. (only use in non-transplant candidate)
• Melphalan-nephrotoxic.
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For younger patients
• High-dose dexamethasone based induction.
• Followed by high-dose melphalan with peripheral blood stem cell rescue (autotransplantation)
• Stem cell transplant- improves survival but not curative.
• CR in 40%.• median survival increasing to 6 years.
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• What agents to use for relapse myeloma?
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• Thalidomide (immunomodulatory derivatives)
• Lenalidomide + dexamethasone. (the above combination is more effective than high-dose
dexamethasone alone in relapsed or refractory multiple myeloma-NEJM)
• Bortezomib (proteosome inhibitor)- higher incidence of herpes zoster.
• 78% improvement in median time to progression with Bortezomib.
• Choice based on side effect profile.
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• What are the prognostic markers of MM?
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Bad prognosis if…
• Raised B2-microglobulin >4.• Low serum albumin <3g/dl.• Cytogenetics –ch13 deletion, hypodiploidy,
T(4:14) • Raised LDH, CRP, Cr.• Low platelet <150 and Hb<100.• Bone marrow plasma cell percentage ≥ 50%• Age >70.
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• What features would make you suspect MGUS?
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MGUS• Monoclonal Gammapathy of Undetermined
Significance.• Asymptomatic patient. Advanced age.• Presence of low serum M-protein <3 g/dL• No evidence of myeloma.• Minimal infiltrate of bone marrow (<10%)• IgG most common (70%).• BJP negative (69%)• Overall risk of progression= 1% per year.• No treatment is required.
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• What is the most important risk factor for progression of MGUS to plasma cell cancer?
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• M band size. The bigger, the worse.
• IgM or IgA monoclonal protein has increased risk.
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• If a patient is found to have high levels of IgM paraprotein?
• What is the most likely diagnosis?
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• Waldenstrom Macroglobulinemia.
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• What are the side effects of Thalidomide?
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• Constipation• Somnelence.• Painful neuropathy- major side effect.