GAMMOPATIE MONOCLONALI. ACETATO DI CELLULOSA ROSSO PONCEAU.

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Transcript of GAMMOPATIE MONOCLONALI. ACETATO DI CELLULOSA ROSSO PONCEAU.

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GAMMOPATIE MONOCLONALI Slide 2 ACETATO DI CELLULOSA ROSSO PONCEAU Slide 3 Slide 4 Slide 5 ACETATO CELLULOSA AGAROSIO Slide 6 Slide 7 Slide 8 Slide 9 STABLE PROGRESSIVE Slide 10 BENIGN MONOCLONAL GAMMOPATHY DOES EXIST ? frequency Percentage of neoplastic transformation M. Boccadoro www.mieloma.it DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 11 ASYMPTOMATIC NO OSTEOLYTIC LESIONS M-COMPONENT BENIGN MONOCLONAL GAMMOPATHY DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 12 STABLE PROGRESSIVE MONOCLONAL GAMMOPATHIES MDD NN DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 13 Multistep cancerogenesis of myeloma Normal plasma cell MonoclonalgammopathyMyelomaExtra-medullarymyelomaChromosometranslocation IgH switch region Kariotipic instability K, N-ras, P53 mutations DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 14 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 Slide 15 BENIGN MONOCLONAL GAMMOPATHY MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE MGUS MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE MGUS DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 16 FREQUENCY OF MONOCLONAL GAMMOPATHIES GAMMOPATHIES Related to the sensitivity of the method Related to the sensitivity of the method DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 17 1-2 % normal population > 10 g/L Detected by standard methods Detected by sensitive methods ~ 10 % normal population < 5 g/L MONOCLONAL GAMMOPATHIES DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 18 - Out-patients referred for routine laboratory tests - Ospedale Evangelico Valdese, Torino - Laboratorio analisi (Director: M. Saitta) - routine agarose electrophoresis (Hydrasis Ciampolini) (Hydrasis Ciampolini) - period: Genuary- May 1998 - 3013 serum samples analysed - 128 monoclonal gammopathies detected (4.2%) OCCURRENCE OF MONOCLONAL GAMMOPATHIES IN A GENERAL HOSPITAL DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 19 FREQUENCY OF MONOCLONAL GAMMOPATHY ACCORDING TO AGE % DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 20 DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/L) Aguzzi et al, Eur J Haematol, 1992 DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 21 DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/L) DISTRIBUTION OF M-COMPONENT CONCENTRATION (g/L) DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Ospedale Evangelico Valdese, Torino Slide 22 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 Slide 23 MONOCLONAL GAMMOPATHY PROBABILITY OF TRANSFORMATION FOR PATIENTS WITH M-component > 15 15Slide 24 Neoplastic transformation is related to the M-component concentration MONOCLONAL GAMMOPATHY IgG 50 g/L require chemotherapy IgG > 30 g/L transformation within 1 year (Dimopoulos, 1993) IgG > 15 15 < 30 g/L 26% transformation after 10 years (Kyle, 1995) DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 25 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 Slide 26 MONOCLONAL GAMMOPATHIES Related to M-component level Related to M-component level DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY TRANSFORMATION TO MYELOMA Slide 27 BENIGN MONOCLONAL GAMMOPATHY MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE MULTIPLE MYELOMA ~ 70% < 10 g/L ~ 4-6% 10-20 g/L 30 g/L DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 28 BENIGN MONOCLONAL GAMMOPATHY DOES EXIST? PROSPECTIVE LARGE STUDIES ON PATIENTS WITH SMALL M-COMPONENTS ARE REQUIRED PROBABLY YES DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 29 The New England Journal of Medicine DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 30 Multistep cancerogenesis of myeloma Normal plasma cell MonoclonalgammopathyMyelomaExtra-medullarymyelomaChromosometranslocation IgH switch region Kariotipic instability K, N-ras, P53 mutations DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY Slide 31 TRANSFORMATION BENIGN PRE-NEOPLASTIC FROMTO Slide 32 Slide 33 Slide 34 ITALIAN MULTIPLE MYELOMA STUDY GROUP A. Pileri Principal investigators A. Palumbo P. Omed 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 DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY