1. GAMMOPATIE MONOCLONALI

2. ACETATO DI CELLULOSA
ROSSO PONCEAU

5. ACETATO
CELLULOSA
AGAROSIO

9. STABLE
PROGRESSIVE

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

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

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

13. 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

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

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

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

17. 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

18. - 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
serum samples analysed
- 128 monoclonal gammopathies detected (4.2%)
DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

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

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

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

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

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

24. 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

25. A pre-neoplastic disorder?
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
DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

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

27. 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

28. 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

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

30. 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

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

34. 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