GAMMOPATIE MONOCLONALI

ACETATO DI CELLULOSA ROSSO PONCEAU

ACETATO CELLULOSA AGAROSIO

STABLE PROGRESSIVE

BENIGN MONOCLONAL GAMMOPATHY DOES EXIST? frequency Percentage of neoplastic transformation M. Boccadoro DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY www.mieloma.it

BENIGN MONOCLONAL GAMMOPATHY M-COMPONENT ASYMPTOMATIC NO OSTEOLYTIC LESIONS DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

MONOCLONAL GAMMOPATHIES STABLE MDD PROGRESSIVE NN DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

Multistep cancerogenesis of myeloma Normal plasma cell Monoclonal gammopathy Myeloma Extra- medullary myeloma Kariotipic instability K, N-ras, P53 mutations Chromosome translocation IgH switch region DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

Incidence of Multiple Myeloma, macroglobulinemia, amyloidosis after recognition of M-component Kyle R.A., Baillieres Clin Hematol, 1995 DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE BENIGN MONOCLONAL GAMMOPATHY MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE MGUS DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

FREQUENCY OF MONOCLONAL GAMMOPATHIES Related to the sensitivity of the method DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

MONOCLONAL GAMMOPATHIES Detected by standard methods 1-2 % normal population > 10 g/L Detected by sensitive methods ~ 10 % normal population < 5 g/L DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

- 128 monoclonal gammopathies detected (4.2%) 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 1998 - 3013 serum samples analysed - 128 monoclonal gammopathies detected (4.2%) DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

FREQUENCY OF MONOCLONAL GAMMOPATHY ACCORDING TO AGE % DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/L) Aguzzi et al, Eur J Haematol, 1992 DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/L) Ospedale Evangelico Valdese, Torino DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

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

MONOCLONAL GAMMOPATHY PROBABILITY OF TRANSFORMATION FOR PATIENTS WITH M-component > 15 <30 g/L DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

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 (Dimopoulos, 1993) IgG > 15 < 30 g/L 26% transformation after 10 years (Kyle, 1995) IgG<15 g/L 1.3% transformation after 6 years (Baldini, 1996) DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

A pre-neoplastic disorder? BENIGN MONOCLONAL GAMMOPATHY A pre-neoplastic disorder? - 5% frequency M-component - incidence of myeloma 2-4/100.000/year 1 out of 1.000-2000 M-component is transformed to myeloma every year DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

MONOCLONAL GAMMOPATHIES TRANSFORMATION TO MYELOMA Related to M-component level DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

BENIGN MONOCLONAL GAMMOPATHY ~ 70% < 10 g/L BENIGN MONOCLONAL GAMMOPATHY MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE MULTIPLE MYELOMA ~ 4-6% 10-20 g/L 30 g/L DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

BENIGN MONOCLONAL GAMMOPATHY DOES EXIST? PROBABLY YES PROSPECTIVE LARGE STUDIES ON PATIENTS WITH SMALL M-COMPONENTS ARE REQUIRED DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

The New England Journal of Medicine DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

Multistep cancerogenesis of myeloma Normal plasma cell Monoclonal gammopathy Myeloma Extra- medullary myeloma Kariotipic instability K, N-ras, P53 mutations Chromosome translocation IgH switch region DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

TRANSFORMATION FROM TO BENIGN PRE-NEOPLASTIC DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

ITALIAN MULTIPLE MYELOMA STUDY GROUP DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Principal investigators A. Pileri A. Palumbo P. Omedè M.Ladetto M. Massaia B. Bruno S. Battaglio Investigators: S. Bringhen, A. Bertola, G. Aitoro, F. Cavallo, P. Falco, L. Giaccone. R. Ghignone, F. Giaretta, F. Morrone, M. Ruggeri ITALIAN MULTIPLE MYELOMA STUDY GROUP