Multiple Myeloma <ul><li>Definition: </li></ul><ul><li>  B-cell malignancy  characterised  by  abnormal proliferation of p...
Multiple Myeloma <ul><li>Clinical forms: </li></ul><ul><li>  multiple myeloma </li></ul><ul><li>  solitary plasmacytoma </...
Multiple Myeloma <ul><li>Clinical manifestations are related to malignant  </li></ul><ul><li>behavior of plasma cells and ...
Multiple Myeloma <ul><li>Clinical symptoms: </li></ul><ul><li>bone pains, pathologic fractures </li></ul><ul><li>weakness ...
Multiple Myeloma <ul><li>Laboratory tests: </li></ul><ul><li>ESR > 100 </li></ul><ul><li>anaemia, thrombocytopenia </li></...
Diagnostic Criteria for Multiple Myeloma <ul><li>Major criteria   </li></ul><ul><li>I. Plasmacytoma on tissue biopsy </li>...
Diagnostic Criteria for Multiple Myeloma <ul><li>Diagnosis: </li></ul><ul><li>I + b,  I + c,  I + d  </li></ul><ul><li>II ...
Staging of Multiple Myeloma <ul><li>Clinical staging  </li></ul><ul><li>is based on level of haemoglobin,  serum calcium, ...
Multiple Myeloma <ul><li>Poor prognosis factors </li></ul><ul><li>cytogenetical abnormalities of 11 and 13 chromosomes </l...
Treatment of  Multiple Myeloma <ul><li>Patients < 65 - 70 years  </li></ul><ul><ul><li>high-dose therapy with autologous s...
Treatment of  Multiple Myeloma <ul><li>Conventional chemotherapy </li></ul><ul><ul><li>Melphlan + Prednisone </li></ul></u...
Treatment of  Multiple Myeloma <ul><li>Autologous transplantation </li></ul><ul><ul><li>patients < 65-70 years </li></ul><...
Treatment of  Multiple Myeloma <ul><li>New method </li></ul><ul><ul><li>non-myeloablative therapy and allogeneic transplan...
Treatment of  Multiple Myeloma <ul><li>Supportive treatment </li></ul><ul><ul><li>biphosphonates, calcitonin </li></ul></u...
Disorder Associated with Monoclonal Protein <ul><li>Neoplastic cell proliferation </li></ul><ul><ul><li>multiple myeloma <...
Monoclonal gammopathy of undetermined significance ( MGUS)  <ul><li>M protein presence, stable  </li></ul><ul><li>levels o...
Monoclonal gammopathy of undetermined significance ( MGUS) <ul><li>M protein </li></ul><ul><ul><li>3% of people > 70 years...
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Medicine 5th year, 5th lecture/part three (Dr. Abdulla Sharief)

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The lecture has been given on May 12th, 2011 by Dr. Abdulla Sharief.

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Medicine 5th year, 5th lecture/part three (Dr. Abdulla Sharief)

  1. 1. Multiple Myeloma <ul><li>Definition: </li></ul><ul><li> B-cell malignancy characterised by abnormal proliferation of plasma cells able to produce a monoclonal immunoglobulin ( M protein ) </li></ul><ul><li>Incidence: </li></ul><ul><li>3 - 9 cases per 100000 population / year </li></ul><ul><li>more frequent in elderly </li></ul><ul><li>modest male predominance </li></ul>
  2. 2. Multiple Myeloma <ul><li>Clinical forms: </li></ul><ul><li> multiple myeloma </li></ul><ul><li> solitary plasmacytoma </li></ul><ul><li> plasma cell leukemia </li></ul><ul><li>M protein: </li></ul><ul><li>- is seen in 99% of cases in serum and/or urine </li></ul><ul><li>IgG > 50%, IgA 20-25%, IgE i IgD 1-3% </li></ul><ul><li>light chain 20% </li></ul><ul><li>- 1% of cases are nonsecretory </li></ul>
  3. 3. Multiple Myeloma <ul><li>Clinical manifestations are related to malignant </li></ul><ul><li>behavior of plasma cells and abnormalities produced </li></ul><ul><li>by M protein </li></ul><ul><li>plasma cell proliferation: </li></ul><ul><li>multiple osteolytic bone lesions </li></ul><ul><li>hypercalcemia </li></ul><ul><li>bone marrow suppression ( pancytopenia ) </li></ul><ul><li>monoclonal M protein </li></ul><ul><li>decreased level of normal immunoglobulins </li></ul><ul><li>hyperviscosity </li></ul>
  4. 4. Multiple Myeloma <ul><li>Clinical symptoms: </li></ul><ul><li>bone pains, pathologic fractures </li></ul><ul><li>weakness and fatigue </li></ul><ul><li>serious infection </li></ul><ul><li>renal failure </li></ul><ul><li>bleeding diathesis </li></ul>
  5. 5. Multiple Myeloma <ul><li>Laboratory tests: </li></ul><ul><li>ESR > 100 </li></ul><ul><li>anaemia, thrombocytopenia </li></ul><ul><li>rouleaux in peripheral blood smears </li></ul><ul><li>marrow plasmacytosis > 10 -15% </li></ul><ul><li>hyperproteinemia </li></ul><ul><li>hypercalcemia </li></ul><ul><li>proteinuria </li></ul><ul><li>azotemia </li></ul>
  6. 6. Diagnostic Criteria for Multiple Myeloma <ul><li>Major criteria </li></ul><ul><li>I. Plasmacytoma on tissue biopsy </li></ul><ul><li>II. Bone marrow plasma cell > 30% </li></ul><ul><li>III. Monoclonal M spike on electrophoresis IgG > 3,5g/dl, </li></ul><ul><li> IgA > 2g/dl, light chain > 1g/dl in 24h urine sample </li></ul><ul><li>Minor criteria </li></ul><ul><li>a. Bone marrow plasma cells 10-30% </li></ul><ul><li>b. M spike but less than above </li></ul><ul><li>c. Lytic bone lesions </li></ul><ul><li>d. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl </li></ul>
  7. 7. Diagnostic Criteria for Multiple Myeloma <ul><li>Diagnosis: </li></ul><ul><li>I + b, I + c, I + d </li></ul><ul><li>II + b, II + c, II + d </li></ul><ul><li>III + a, III + c, I II + d </li></ul><ul><li>a + b + c, a +b + d </li></ul>
  8. 8. Staging of Multiple Myeloma <ul><li>Clinical staging </li></ul><ul><li>is based on level of haemoglobin, serum calcium, immunoglobulins and presence or not of lytic bone lesions </li></ul><ul><li>correlates with myeloma burden and prognosis </li></ul><ul><li>I. Low tumor mass </li></ul><ul><li>II. Intermediate tumor mass </li></ul><ul><li>III. High tumor mass </li></ul><ul><li>subclassification </li></ul><ul><li>A - creatinine < 2mg/dl </li></ul><ul><li>B - creatinine > 2mg/dl </li></ul>
  9. 9. Multiple Myeloma <ul><li>Poor prognosis factors </li></ul><ul><li>cytogenetical abnormalities of 11 and 13 chromosomes </li></ul><ul><li>beta-2 microglobulines > 2,5 ug/ml </li></ul>
  10. 10. Treatment of Multiple Myeloma <ul><li>Patients < 65 - 70 years </li></ul><ul><ul><li>high-dose therapy with autologous stem cell transplantation </li></ul></ul><ul><ul><li>allogeneic stem cell transplantation ( conventional and „mini”) </li></ul></ul><ul><li>Patients > 65 years </li></ul><ul><ul><li>conventional chemotherapy </li></ul></ul><ul><ul><li>non-myeloablative therapy with allogeneic transplantation („mini”) </li></ul></ul>
  11. 11. Treatment of Multiple Myeloma <ul><li>Conventional chemotherapy </li></ul><ul><ul><li>Melphlan + Prednisone </li></ul></ul><ul><ul><li>M2 ( Vincristine, Melphalan, Cyclophosphamid, BCNU, Prednisone) </li></ul></ul><ul><ul><li>VAD (Vincristin, Adriamycin, Dexamethasone) </li></ul></ul><ul><li>Response rate 50-60% patients </li></ul><ul><li>Long term survival 5-10% patients </li></ul>
  12. 12. Treatment of Multiple Myeloma <ul><li>Autologous transplantation </li></ul><ul><ul><li>patients < 65-70 years </li></ul></ul><ul><ul><li>treatment related mortality 10-20% </li></ul></ul><ul><ul><li>response rate 80% </li></ul></ul><ul><ul><li>long term survival 40-50% </li></ul></ul><ul><li>Conventional allogeneic transplantation </li></ul><ul><ul><li>patients < 45-50 years with HLA-identical donor </li></ul></ul><ul><ul><li>treatment related mortality 40-50% </li></ul></ul><ul><ul><li>long term survival 20-30% </li></ul></ul>
  13. 13. Treatment of Multiple Myeloma <ul><li>New method </li></ul><ul><ul><li>non-myeloablative therapy and allogeneic transplantation </li></ul></ul><ul><ul><li>thalidomid </li></ul></ul>
  14. 14. Treatment of Multiple Myeloma <ul><li>Supportive treatment </li></ul><ul><ul><li>biphosphonates, calcitonin </li></ul></ul><ul><ul><li>recombinant erythropoietin </li></ul></ul><ul><ul><li>immunoglobulins </li></ul></ul><ul><ul><li>plasma exchange </li></ul></ul><ul><ul><li>radiation therapy </li></ul></ul>
  15. 15. Disorder Associated with Monoclonal Protein <ul><li>Neoplastic cell proliferation </li></ul><ul><ul><li>multiple myeloma </li></ul></ul><ul><ul><li>solitary plasmacytoma </li></ul></ul><ul><ul><li>Waldenstrom macroglobulinemia </li></ul></ul><ul><ul><li>heavy chain disease </li></ul></ul><ul><ul><li>primary amyloidosis </li></ul></ul><ul><li>Undetermined significance </li></ul><ul><ul><li>monoclonal gammopathy of undetermined significance (MGUS) </li></ul></ul><ul><li>Transient M protein </li></ul><ul><ul><li>viral infection </li></ul></ul><ul><ul><li>post-valve replacement </li></ul></ul><ul><li>Malignacy </li></ul><ul><ul><li>bowel cancer, breast cancer </li></ul></ul><ul><li>Immune dysregulation </li></ul><ul><ul><li>AIDS, old age </li></ul></ul><ul><li>Chronic inflamation </li></ul>
  16. 16. Monoclonal gammopathy of undetermined significance ( MGUS) <ul><li>M protein presence, stable </li></ul><ul><li>levels of M protein: IgG < 3,5g IgA < 2g LC<1g/day </li></ul><ul><li>normal immunoglobulins - normal levels </li></ul><ul><li>marrow plasmacytosis < 5% </li></ul><ul><li>complete blood count - normal </li></ul><ul><li>no lytic bone lesions </li></ul><ul><li>no signs of disease </li></ul>
  17. 17. Monoclonal gammopathy of undetermined significance ( MGUS) <ul><li>M protein </li></ul><ul><ul><li>3% of people > 70 years </li></ul></ul><ul><ul><li>15% of people > 90 years </li></ul></ul><ul><ul><li>MGUS is diagnosed in 67% of patients with an M protein </li></ul></ul><ul><ul><li>10% of patients with MGUS develop multiple myeloma </li></ul></ul>

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