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LE GAMMOPATIE MONOCLONALI

LE GAMMOPATIE MONOCLONALI. Enrico Capochiani - Ematologia, Livorno. DEFINIZIONE.

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LE GAMMOPATIE MONOCLONALI

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  1. LE GAMMOPATIE MONOCLONALI Enrico Capochiani - Ematologia, Livorno

  2. DEFINIZIONE 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)

  3. Classificazione GAMMOPATIE MONOCLONALI NEOPLASTICHE • Mieloma multiplo • Plasmacitoma localizzato • Leucemia plasmacellulare • Macroglobulinemia di Waldenstrom GAMMOPATIA MONOCLONALE DI SIGNIFICATO NON DETERMINATO (MGUS)

  4. GAMMOPATIA MONOCLONALE DI 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’età • Non necessita di terapia

  5. Incidenza • Soprai 50 aa: incidenzapari a 3.2% • 50-59: 1.7 % • >70; 5.3% • Piùfrequenteneimaschi e negli Afro-Americani • Il rischiodiprogressione a mielomamultiplo: 1%/anno • Indipendentedall’età • Dipendentedaifattoriprognostici

  6. INCIDENZA DELLA MGUS SECONDO L’ETA’

  7. Probabilità di progressione da MGUS a MM increase progression

  8. Produzione 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.

  9. Componente M: tipologia

  10. Smouldering myeloma 4% Lymphoma 5% Multiple Myeloma 18% (185) Amyloidosis (AL) 10% Solitary or extramedullaryplasmacytoma 3% Chronic lymphocytic leukaemia 2% (21) Waldenström’s macroglobulinaemia 2% (20) MGUS 56% (578) Componente M: classificazione per patologia

  11. Patologie 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)

  12. MM: i criteri diagnostici di D&S • Major criteria • - plasmacytoma • - > 30% plasma cells in BM • - M-protein serum • IgG > 35 g/l • IgA > 20 g/l • light chains urine • > I g / 24 h • Minor criteria • -10-30% plasma cells in BM • - protein < major • - steolytic lesions • - Normal Ig decreased • IgG , 6 g/l • IgA < 1 g/l • IgM < o.5 g/l

  13. MM: i criteri diagnostici attuali MGUS Asymptomatic Symptomatic myeloma 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 associated organ/tissue impairment organ/tissue impairment organ/tissue impairment (ROTI) No B-cell NHL No amyloidosis No other diseases

  14. MGUS: i fattori prognostici • Componente M sierica >15 g/l • Non-IgG MGUS • Rapporto tra catene leggere K e L sieriche anormale (FLC ratio)

  15. Ratio K/L

  16. Filtrazione e riassorbimento renale • (monomer) 25 kDa  (dimer) 50 kDa Glomerulus 40-60 kDa pores light chain filtered Distal Tubule 10-30g/day reabsorption Proximal Tubule 10-30g/day reabsorption 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.

  17. Rischio evolutivo a MM

  18. Rischio di progressione: FLC ratio

  19. Altri indicatori predittivi • Immunofenotipo • PC normali: CD138+ CD19 + CD56 -- policlonali • PC patologiche: CD138+ CD19 -- CD56+ monoclonali

  20. MGUS working party IMWG • 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)

  21. Follow up

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