BENIGN MONOCLONAL GAMMOPATHY

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1 BENIGN MONOCLONAL GAMMOPATHY DOES EXIST? frequency Percentage of neoplastic transformation M. Boccadoro

2 BENIGN MONOCLONAL GAMMOPATHY M-COMPONENT ASYMPTOMATIC NO OSTEOLYTIC LESIONS

3 MONOCLONAL GAMMOPATHIES STABLE MDD PROGRESSIVE NN

4 Multistep cancerogenesis of myeloma Normal plasma cell Monoclonal gammopathy Myeloma Extra- medullary myeloma Kariotipic instability Chromosome translocation IgH switch region K, N-ras ras,, P53 mutations

5 Incidence of Multiple Myeloma, macroglobulinemia, amyloidosis after recognition of M-component Kyle R.A., Baillieres Clin Hematol, 1995

6 BENIGN MONOCLONAL GAMMOPATHY MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE MGUS

7 FREQUENCY OF MONOCLONAL GAMMOPATHIES Related to the sensitivity of the method

8 MONOCLONAL GAMMOPATHIES MONOCLONAL GAMMOPATHIES Detected by standard methods Detected by standard methods 1-2 % normal population > 10 g/l Detected by sensitive methods Detected by sensitive methods ~ 10 % normal population < 5 g/l

9 OCCURRENCE OF MONOCLONAL GAMMOPATHIES IN A GENERAL HOSPITAL - Out-patients referred for routine laboratory tests - Ospedale Evangelico Valdese, Torino - Laboratorio analisi (Director: M. Saitta) - routine agarose electrophoresis (Hydrasis Ciampolini) - period: Genuary- - May serum samples analysed monoclonal gammopathies detected (4.2%)

10 FREQUENCY OF MONOCLONAL GAMMOPATHY ACCORDING TO AGE % < >80

11 DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/l) % % > 20 2% n.q. 2% Aguzzi et al, Eur J Haematol, 1992 < 5 g/l 78%

12 DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/l) 12% 9% 2% 77% g/l<10 >10 g/l <15 >15 g/l <30 g/l >30

13 MONOCLONAL GAMMOPATHY MONOCLONAL GAMMOPATHY PROBABILITY OF TRANSFORMATION TO A MALIGNANT DISEASE Evaluated in patient series: Evaluated in patient series: Diagnosis 1960s - 70s Diagnosis 1960s - 70s Standard electrophoresis Standard electrophoresis M-component at presentation >15 g/l M-component at presentation >15 g/l DIVISIONE DIVISIONE UNIVERSITARIA UNIVERSITARIA DI DI EMATOLOGIA EMATOLOGIA AZIENDA AZIENDA OSPEDALIERA OSPEDALIERA SAN SAN GIOVANNI GIOVANNI TORINO, TORINO, ITALY ITALY

14 MONOCLONAL GAMMOPATHY PROBABILITY OF TRANSFORMATION FOR PATIENTS WITH M-component > 15 <30 g/l 12% 9% 2% 77%

15 MONOCLONAL GAMMOPATHY Neoplastic transformation is related to the M-component concentration IgG > 50 g/l require chemotherapy IgG > 30 g/l transformation within 1 year year (Dimopoulos,, 1993) IgG > 15 < 30 g/l 26% transformation after 10 years years (Kyle,, 1995) IgG<15 g/l 1.3% transformation after 6 years years (Baldini,, 1996)

16 BENIGN MONOCLONAL GAMMOPATHY A pre-neoplastic disorder? - 5% frequency M-component - incidence of myeloma 2-4/ /year 1 out of M-component is transformed to myeloma every year

17 BENIGN MONOCLONAL GAMMOPATHY DOES EXIST? PROBABLY YES PROSPECTIVE LARGE STUDIES ON PATIENTS WITH SMALL M-COMPONENTS ARE REQUIRED (definitive results available in 2015)

18 ~ 70% < 10 g/l BENIGN MONOCLONAL GAMMOPATHY ~ 4-6% g/l MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE 30 g/l MULTIPLE MYELOMA MULTIPLE MYELOMA

19 TRANSFORMATION FROM TO BENIGN PRE-NEOPLASTIC