multiple myeloma definition: b-cell malignancy characterised by abnormal proliferation of plasma...
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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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Multiple Myeloma
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Multiple Myeloma
Clinical symptoms:
• bone pains, pathologic fractures• weakness and fatigue • serious infection • renal failure• bleeding diathesis
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Multiple Myeloma
Laboratory tests:• ESR > 100• anaemia, thrombocytopenia• rouleaux in peripheral blood smears• marrow plasmocytosis > 10 %• hyperproteinemia• hypercalcemia• proteinuria
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Multiple myeloma INITIAL DIAGNOSTIC WORKUP
2011
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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
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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
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Multiple Myeloma
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Diagnostic Criteria for Multiple Myeloma (present)
–Plasmocytosis >= 10% and/or plazmocytoma infiltration
–M protein
– Myeloma related damage (CRAB)
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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)
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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
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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
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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/dlB - creatinine > 2mg/dl
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ISS (International Staging System for multiple myeloma)
Stage MOS (months)
I β2 microglobulin < 3,5 mg/l and albumins > 3,5 g/dl
62
II No criteria for I and III 44
III β2 mikroglobulin >5,5 mg/l 29
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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)
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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%
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MM treatment
• Bortesomib
– Reversible proteasoms’ inhibitor
– NFκB inhibitor (promotes apoptosis)
– registered for 2nd and 3rd line
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Multiple myeloma diagnosis
Pt qualified for auto PBSCT (younger than 65) Older than 65
or not qualified for PBSCT
MelphalanPrednisone
Thalidomide
Thalidomide Dexamethasone
Mobilization chemotherapy and collection of stemm cells
Melphalan 200 mg and PBSCT
Thalidomide as sustaining treatment ?
Thalidomide as sustaining treatment ?
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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.
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Treatment of Multiple Myeloma
• New methods– Non-myeloablative therapy and allogeneic
transplantation– Tandem transplants– Bortesomib (proteasome inhibitor)– Lenalidomide– Arsenic trioxide – Statins
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Treatment of Multiple Myeloma
• Supportive treatment– biphosphonates, calcitonin– recombinant erythropoietin– immunoglobulins– plasma exchange – radiation therapy
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2011
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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