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Multiple Myeloma

Multiple Myeloma. Definition: B-cell malignancy characterised by abnormal proliferation of plasma cells able to produce a monoclonal immunoglobulin (M protein) Incidence: 3 - 9 cases per 100000 population / year more frequent in elderly modest male predominance.

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Multiple Myeloma

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  1. Multiple Myeloma • Definition: B-cell malignancy characterised by abnormal proliferation of plasma cells able to produce a monoclonal immunoglobulin (M protein) • Incidence: 3 - 9 cases per 100000 population / year more frequent in elderly modest male predominance

  2. Multiple myeloma

  3. Multiple Myeloma

  4. Multiple Myeloma Clinical symptoms: • bone pains, pathologic fractures • weakness and fatigue • serious infection • renal failure • bleeding diathesis

  5. Multiple Myeloma Laboratory tests: • ESR > 100 • anaemia, thrombocytopenia • rouleaux in peripheral blood smears • marrow plasmocytosis > 10 % • hyperproteinemia • hypercalcemia • proteinuria

  6. 2011 Multiple myeloma INITIAL DIAGNOSTIC WORKUP

  7. Diagnostic Criteria for Multiple Myeloma (old) Major criteria I. Plasmacytoma on tissue biopsy II. Bone marrow plasma cell > 30% III. Monoclonal M spike on electrophoresis IgG > 3,5g/dl, IgA > 2g/dl, light chain > 1g/dl in 24h urine sample Minor criteria a. Bone marrow plasma cells 10-30% b. M spike but less than above c. Lytic bone lesions d. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl

  8. Diagnostic Criteria for Multiple Myeloma Diagnosis: • I + b, I + c, I + d • II + b, II + c, II + d • III + a, III + c, I II + d • a + b + c, a +b + d

  9. Multiple Myeloma

  10. Diagnostic Criteria for Multiple Myeloma (present) • Plasmocytosis >= 10% and/or plazmocytoma infiltration • M protein • Myeloma related damage (CRAB)

  11. Diagnostic Criteria for Multiple Myeloma (present) • C (Calcium) (> 2,75 mmol/l) • R (Renal Insufficiency) creatinine concentration >173 mmol/l (1,96 mg/dl) • A (Anemia) Hg <10 g/dl • B (Bone lesions)

  12. Monoclonal gammopathy of undetermined significance ( MGUS) • M protein present, stable • levels of M protein: IgG < 3,0g IgA < 2g LC<1g/day • normal immunoglobulins - normal levels • marrow plasmacytosis < 10% • complete blood count - normal • no lytic bone lesions • no signs of disease

  13. Smouldering multiple myeloma • M protein present, stable • levels of M protein: IgG  3,0g IgA  2g LC1g/day • normal immunoglobulins - normal levels • marrow plasmacytosis 10% • complete blood count - normal • no lytic bone lesions • no signs of disease

  14. Staging of Multiple Myeloma Clinical staging (Salmon-Durie) • is based on level of haemoglobin, serum calcium, immunoglobulins and presence or not of lytic bone lesions • correlates with myeloma burden and prognosis I. Low tumor mass II. Intermediate tumor mass III. High tumor mass • subclassification A - creatinine < 2mg/dl B - creatinine > 2mg/dl

  15. ISS (International Staging System for multiple myeloma)

  16. MM treatment • Thalidomide • TNF-α inhibitor • b-FGF and VEGF2 inhibitor (antiangiogenic factor) • Apoptosis promotion ( NF-κB ) • Induktion of Th1 activity with production of IFN-γ i IL-2)

  17. MM treatment • MP („gold standard” ) • Melfalan 9 mg/m2 po 1-4 day every 6 weeks • Prednison 60 mg/m2 po 1-4 day every 6 weeks • Up to 9 cycles • OR (CR+PR+MR) 47% • OS 32 months • Infections (3 i 4 NCI grade) 18%

  18. MM treatment • Bortesomib • Reversible proteasoms’ inhibitor • NFκB inhibitor (promotes apoptosis) • registered for 2nd and 3rd line

  19. Treatment of Multiple Myeloma Event-free and overall survival times of 515 patients receiving autotransplants and a median follow-up of at least 5 years.

  20. Treatment of Multiple Myeloma • New methods • Non-myeloablative therapy and allogeneic transplantation • Tandem transplants • Bortesomib (proteasome inhibitor) • Lenalidomide • Arsenic trioxide • Statins

  21. Treatment of Multiple Myeloma • Supportive treatment • biphosphonates, calcitonin • recombinant erythropoietin • immunoglobulins • plasma exchange • radiation therapy

  22. 2011

  23. Disorder Associated with Monoclonal Protein • Neoplastic cell proliferation • multiple myeloma • solitary plasmacytoma • Waldenstrom macroglobulinemia • heavy chain disease • primary amyloidosis • Undetermined significance • monoclonal gammopathy of undetermined significance (MGUS) • Transient M protein • viral infection • post-valve replacement • Malignacy • bowel cancer, breast cancer • Immune dysregulation • AIDS, old age • Chronic inflamation

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