le gammopatie monoclonali enrico capochiani - ematologia, livorno
TRANSCRIPT
![Page 1: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/1.jpg)
LE GAMMOPATIE MONOCLONALILE GAMMOPATIE MONOCLONALI
Enrico Capochiani - Ematologia, Livorno
![Page 2: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/2.jpg)
DEFINIZIONEDEFINIZIONE
Le gammapatie monoclonali sono quadri clinico-laboratoristici caratterizzati dalla proliferazione e accumulo nel midollo osseo di un clone di linfociti B e plasmacellule sintetizzanti immunoglobuline (Ig) identiche per caratteristiche isotipiche (stessa classe di Ig) e idiotipiche (stesso sito di legame con l’antigene nella regione variabile), complete o incomplete, rilevabili nel siero e/o nelle urine.
Tali Ig prendono il nome di Componente monoclonale (CM)
![Page 3: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/3.jpg)
ClassificazioneClassificazione
GAMMOPATIE MONOCLONALI NEOPLASTICHE
GAMMOPATIA MONOCLONALE DI SIGNIFICATO NON DETERMINATO (MGUS)
•Mieloma multiplo
•Plasmacitoma localizzato
•Leucemia plasmacellulare
•Macroglobulinemia di Waldenstrom
![Page 4: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/4.jpg)
GAMMOPATIA MONOCLONALE DI GAMMOPATIA MONOCLONALE DI SIGNIFICATO NON DETERMINATO (MGUS)SIGNIFICATO NON DETERMINATO (MGUS)
Diagnosi occasionale in corso di accertamenti laboratoristici
La clinica è per definizione assente (nessun sintomo o danno d’organo)
L’incidenza aumenta con l’etàNon necessita di terapia
![Page 5: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/5.jpg)
IncidenzaIncidenza
Sopra i 50 aa: incidenza pari a 3.2%50-59: 1.7 %>70; 5.3%
Più frequente nei maschi e negli Afro-Americani
Il rischio di progressione a mieloma multiplo: 1%/anno
Indipendente dall’età
Dipendente dai fattori prognostici
![Page 6: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/6.jpg)
INCIDENZA DELLA MGUS SECONDO L’ETA’INCIDENZA DELLA MGUS SECONDO L’ETA’
![Page 7: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/7.jpg)
Probabilità di progressione da MGUS a Probabilità di progressione da MGUS a MMMM
increase
progression
![Page 8: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/8.jpg)
Produzione di catene leggere libereProduzione di catene leggere libere
The plasma cells produce one of five heavy chain types and one of two light chains i.e. kappa or lambda. There is approximately 40% excess of free light chain production to allow proper conformation during synthesis of the intact immunoglobulin molecule. There are twice as many kappa producing plasma cells as lambda and the kappa is normally monomeric, while the lambda tends to be dimeric with disulphide bonds. This is relevant to serum concentrations because the larger size of the lambda molecules slows their metabolism.
![Page 9: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/9.jpg)
Componente M: tipologiaComponente M: tipologia
60.0%20.0%
10.0%
7.0%
3.0% 0.1%
0.0%
IgG IgM IgA L-keten Biclonaal IgD IgE
![Page 10: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/10.jpg)
Componente M: classificazione per patologiaComponente M: classificazione per patologia
Solitary or extramedullary plasmacytoma 3%
Chronic lymphocytic leukaemia 2% (21)
Waldenström’s macroglobulinaemia 2% (20)MGUS
56% (578)
Multiple Myeloma 18%
(185)
Lymphoma 5%
Amyloidosis (AL) 10%
Smouldering myeloma 4%
![Page 11: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/11.jpg)
Patologie associate o associabili a MGUSPatologie associate o associabili a MGUS
Malattie autoimmuni (AR, LES, sclerodermia, connettivopatie minori, ecc)
Malattie cutanee (Psoriasi, parapsoriase, pyoderma gangraenoso, pemfigo, ecc)
Patologie epatiche e gastroenteriche (cirrosi, RCU, Crohn, celiachia, ecc)
Patologie infettive (m.tubercolare, HVC, HBV, HIV, H.Pylori, )
Patologie con stimolo immonogeno continuativo (antigen driven)
![Page 12: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/12.jpg)
MM: i criteri diagnostici di D&SMM: i criteri diagnostici di D&S
Major criteria
- plasmacytoma- > 30% plasma cells in BM- M-protein serum
IgG > 35 g/lIgA > 20 g/llight chains urine> I g / 24 h
Minor criteria
-10-30% plasma cells in BM- protein < major- steolytic lesions- Normal Ig decreased
IgG , 6 g/lIgA < 1 g/lIgM < o.5 g/l
![Page 13: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/13.jpg)
MM: i criteri diagnostici attualiMM: i criteri diagnostici attuali
MGUS Asymptomatic Symptomaticmyeloma myeloma
M-protein < 30 g/l M-protein > 30 g/l M-protein present
BM clonal plasmacells BM clonal plasmacells BM clonal plasmacells< 10% > 10% any %
No myeloma associated No myeloma associated Any myeloma associatedorgan/tissue impairment organ/tissue impairment organ/tissue impairment
(ROTI)
No B-cell NHLNo amyloidosisNo other diseases
MGUS Asymptomatic Symptomaticmyeloma myeloma
M-protein < 30 g/l M-protein > 30 g/l M-protein present
BM clonal plasmacells BM clonal plasmacells BM clonal plasmacells< 10% > 10% any %
No myeloma associated No myeloma associated Any myeloma associatedorgan/tissue impairment organ/tissue impairment organ/tissue impairment
(ROTI)
No B-cell NHLNo amyloidosisNo other diseases
![Page 14: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/14.jpg)
MGUS: i fattori prognosticiMGUS: i fattori prognostici
Componente M sierica >15 g/l
Non-IgG MGUS
Rapporto tra catene leggere K e L sieriche anormale (FLC ratio)
![Page 15: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/15.jpg)
Normal serum mean median 95 %concentration concentration range
Free Kappa 8,36 mg/l 7,30 mg/l 3,30 – 19,40 mg/l
Free Lambda 13,43 mg/l 12,40 mg/l 5,71 – 26,30 mg/l
Kappa/
Lambda ratio
mean median total range
0,63 0,60 0,26 – 1,65
Ratio K/LRatio K/L
![Page 16: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/16.jpg)
Filtrazione e riassorbimento renaleFiltrazione e riassorbimento renale
Glomerulus40-60 kDa poreslight chain filtered
Proximal Tubule10-30g/day reabsorption
(dimer)50 kDa
Distal Tubule10-30g/day reabsorption
(monomer)25 kDa
Kappa monomers, because of their smaller size, filter 3X faster than dimeric lambda molecules. So, although there is a lower production rate, the end result is that normal serum contains more lambda than kappa. Because of the huge proximal tubule reabsorption, the amount of FLC in the urine is heavily dependent upon renal function and less on synthesis by the tumour.
![Page 17: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/17.jpg)
Rischio evolutivo a MMRischio evolutivo a MM
Risk Group DefinitionN°
patientsRelative Risk,
95% CI
Absolute risk of progression at 20 years, %
Low riskSerum M prot<15g/L,
IgG, Normal FLC [0,26-1,65]
449 1 5
Low-intermediate risk
Any 1 factor abnormal 420 5,4 21
High-intermediat risk
Any 2 factors abnormal 226 10,1 37
High risk All 3 factors abnormal 53 20,8 58
Risk stratification model incorporating all 3 predictive factors. Ref 1
![Page 18: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/18.jpg)
Rischio di progressione: FLC ratioRischio di progressione: FLC ratio
![Page 19: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/19.jpg)
Altri indicatori predittiviAltri indicatori predittivi
Immunofenotipo
PC normali: CD138+ CD19 + CD56 -- policlonaliPC patologiche: CD138+ CD19 -- CD56+ monoclonali
![Page 20: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/20.jpg)
MGUS working party MGUS working party IMWGIMWG
LABORATORIO Emocromo Ca, Albumina e creatinina Proteine totali, tracciato e immunofissazione IgG – A – M, catene leggere sieriche Proteinura BJ o meglio albuminura e IF urinaria
RX scheletro solo dopo esami ematochimici e se presente dolore osseo segmentario BOM o aspirato solo se
– CM > 15 g/l– CM è IgA or IgM– FLC ratio anormale
TC torace/addome se CM IgM (M.Waldenstrom)
![Page 21: LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno](https://reader035.vdocuments.site/reader035/viewer/2022081417/5542eb4c497959361e8b9afc/html5/thumbnails/21.jpg)
Follow upFollow up