Medicine.Multiple myeloma.(dr.sabir)

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Medicine.Multiple myeloma.(dr.sabir)

  1. 1. Multiple myeloma Dr. Sabir M. Amin
  2. 2. Definition <ul><li>characterized by neoplastic proliferation of a clone of plasma cells producing a </li></ul><ul><li>monoclonal immunoglobulin </li></ul><ul><li>• usually single clone of plasma cells, although biclonal myeloma has been reported </li></ul>
  3. 3. Epidemiology <ul><li>incidence 3 per 100,000 </li></ul><ul><li>• increased frequency with age, median age of diagnosis is 68 </li></ul>
  4. 4. Pathophysiology <ul><li>malignant plasma cells secrete monoclonal antibody </li></ul><ul><li>95% produce M protein (a monoclonal Ig = identical heavy chain + identical light </li></ul><ul><li>chain) </li></ul><ul><li>• IgG 55%, IgA 20%, IgD 2%, IgM 0.5% </li></ul>
  5. 5. pathophysiology <ul><li>15-20% produce only light chains, found in either: </li></ul><ul><li>• serum as an increase in the quantity of either kappa or lambda light chain </li></ul><ul><li>• urine as Bence-Jones Protein </li></ul><ul><li><5% are non-secretors </li></ul>
  6. 6. Clinical features <ul><li>Bone disease - pain (usually back), bony tenderness. pathologic fractures, lytic lesions are classical (skull, spine, proximal long bones, ribs) </li></ul><ul><li>increased bone resorption secondary to osteoclast activity </li></ul><ul><li>Anemia - weakness, fatigue. Pallor (secondary to BM suppression) </li></ul><ul><li>• weight loss </li></ul><ul><li>Infections: </li></ul><ul><li>usually S. pneumoniae and Gram-negatives </li></ul><ul><li>(secondary to suppression of normal plasma cell function) </li></ul>
  7. 7. Lytic lesions & pathological #
  8. 8. C/F <ul><li>Hypercalcemia – N/V, confusion, constipation, polyuria, polydipsia, secondary to increased bone turnover </li></ul><ul><li>Renal disease/renal failure </li></ul><ul><li>• most frequently causes cast nephropathy </li></ul><ul><li>Bleeding: </li></ul><ul><li>secondary to thrombocytopenia. may see petechiae, purpura </li></ul><ul><li>Extramedullary plasmacytoma: </li></ul><ul><li>soft tissue mass composed of monoclonal plasma cells, purplish colour </li></ul>
  9. 9. C/F <ul><li>Hyperviscosity - may manifest as headaches, stroke, angina, Ml secondary to increased viscosity caused by M (monoclonal) protein </li></ul><ul><li>Amyloidosis: </li></ul><ul><li>may cause Factor X deficiency if fibrils bind Factor X ->bleeding </li></ul><ul><li>Neurologic disease - muscle weakness, pain paresthesias radiculopathy caused by vertebral fracture, extramedullary plasmacytoma. </li></ul><ul><li>spinal cord compression (in 10-20% of pts) is a medical emergency </li></ul>
  10. 10. Investigation <ul><li>CBC </li></ul><ul><li>• normocytic anemia, thrombocytopenia, leukopenia </li></ul><ul><li>• rouleaux formation on peripheral film, ↑ ESR </li></ul><ul><li>Biochemistry </li></ul><ul><li>• increased Ca, increased Cr, proteinuria (24 hour urine collection) </li></ul><ul><li>Serum protein electrophoresis - demonstrates monoclonal protein spike in serum, in 80% - i.e. M protein </li></ul><ul><li>• urine protein electrophoresis - demonstrates light chains in urine =Bence-Jones Protein (20% ) </li></ul>
  11. 11. Investigation <ul><li>bone marrow biopsy </li></ul><ul><li>• greater than 10% plasma cells </li></ul><ul><li>Skeletal series ( x.rays ), MRI if symptoms of cord compression </li></ul><ul><li>• presence of lytic lesions and areas at risk of pathologic fracture </li></ul><ul><li>• beta-2 microglobulin , LDH and CRP are poor prognosticators </li></ul>
  12. 12. BM aspirate: infiltrate of abnormal plasma cells
  13. 13. Diagnosis <ul><li>Minimal diagnostic criteria for myeloma </li></ul><ul><li>• 10% plasma cells in BM or plasmacytoma on biopsy </li></ul><ul><li>• Plus at least one of: </li></ul><ul><li>1.Serum paraprotein (IgG 30 g/l; IgA 20 g/l) </li></ul><ul><li>2.Urine paraprotein (Bence Jones proteinuria) </li></ul><ul><li>3. Osteolytic lesions on skeletal survey </li></ul>
  14. 14. Treatment <ul><li>Treatment is non curative </li></ul><ul><li>Treatment goals are: </li></ul><ul><li>• improvement in quality of life (improve anemia, reverse renal failure, bony pains, prevent progression of disease and complications) </li></ul><ul><li>• increase in overall survival </li></ul><ul><li>• autologous stem cell transplant if <70 year old </li></ul><ul><li>usually preceded by 4-6 months of tumour reducing therapy utilizing a regimen that </li></ul><ul><li>includes steroids (prednisone or dexamethasone) </li></ul>
  15. 15. Treatment <ul><li>chemotherapy if >70 years old or transplant-ineligible </li></ul><ul><li>consider melphalan + prednisone alone if >75 yrs </li></ul><ul><li>Melphalan + prednisone + thalidomide or melphalan + prednisone + bortezomib </li></ul><ul><li>if 65-75 yrs </li></ul><ul><li>dexilmethilsone ± thalidomide, bortezomib if ARF </li></ul>
  16. 16. Treatment <ul><li>supportive management with: </li></ul><ul><li>Bisphosphonates for osteoporosis or lytic lesions </li></ul><ul><li>Local XRT for bone pain, spinal cord compression </li></ul><ul><li>Kyphoplasty/vertebroplasty for vertebral fractures to improve pain relief and regain height(kyphoplasty) </li></ul><ul><li>Hydration for hypercalcemia and renal failure, bisphosphonates (e.g. pamidronate) for severe hypercalcemia, prophylactic antibiotics , erythropoietin for anemia </li></ul>
  17. 17. Monoclonal Gammopathy of Unknown Significance (MGUS) <ul><li>• presence of M protein in serum in absence of any clinical or laboratory evidence of a </li></ul><ul><li>plasma cell dyscrasia or lymphoproliferative disorders </li></ul><ul><li>• incidence: 0.15% in general population, 5% of people >70 years of age </li></ul><ul><li>• asymptomatic </li></ul>
  18. 18. Diagnosis <ul><li>Presence of a serum (M-protein) at a concentration <30 g/L </li></ul><ul><li>• <10% plasma cel[s in bone marrow </li></ul><ul><li>• absence of hyper C alcemia, and R enal insufficiency, A nemia, B ony disease related to the plasma cell proliferative process (absence of &quot;CRAB&quot;) </li></ul><ul><li>. 0.3-1% of patients develop a hematologic malignancy each year </li></ul><ul><li>• patients with M protein peak ≥15 g/L, or patients with IgA or IgM MGUS are at higher risk of malignant transformation </li></ul><ul><li>• patients with a normal free light chain ratio are at low risk </li></ul><ul><li>monitor with annual history, physical, CBC, Cr, Calcium, albumin. serum protein electrophoresis (considered pre-malignant) </li></ul>
  19. 19. Waldenstrom’s macroglobulinemia <ul><li>proliferation of lymphoplasmacytoid cells (a hybrid of lymphocytes and plasma cells) </li></ul><ul><li>• secrete large quantities of monoclonal lgM paraprotein </li></ul>
  20. 20. C/F <ul><li>chronic disorder of elderly patients, median age 64 symptoms: weakness, fatigue, bleeding (oronasal), weight loss, recurrent infections, dyspnea, CHF </li></ul><ul><li>(triad of anemia, hyperviscosity, plasma volume expansion). Neurological symptoms: peripheral neuropathy, cerebral dysfunction </li></ul><ul><li>• signs: pallor, splenomegaly. hepatomegaly. lymphadenopathy, retinal lesions </li></ul><ul><li>• key complication to avoid: Hyperviscosity Syndrome </li></ul><ul><li>because IgM (unlike IgG) confined largely to intravascular space </li></ul>
  21. 21. Investigation & Dx <ul><li>bone marrow shows plasmacytoid lymphocytes </li></ul><ul><li>• bone lesions usually not present </li></ul><ul><li>• rarely hypercalcemia </li></ul><ul><li>• cold hemagglutinin disease possible - Raynaud's phenomenon. hemolytic anemia precipitated by cold weather . normocytic anemia, rouleaux, high ESR if hyperviscosity not present </li></ul>
  22. 22. Treatment <ul><li>alkylating agents (chlorambucil). nucleoside analogues (fludarabine). thalidomide, </li></ul><ul><li>rituximab. or combination therapy </li></ul><ul><li>• corticosteroids </li></ul><ul><li>• plasmapheresis for hyperviscosity </li></ul>

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