or development of malignancies
11 pts reduced CN
con CNI fino al momento della conversione all'altro CNI
-la terapia immunosoppressiva e' stata trattata solo dal punto di vista qualitativo (doppio regime[CNI+ steroidi] versus triplo regime[CNI+ antimetaboliti[azatioprina/micofenolato mofetile/acido micofenolico]] + quadruplo regime).
3.4
Discussione
In questo studio comprendente 1425 pazienti riceventi trapianto di fegato, in un periodo di 17 anni, i tumori de novo sono stati identificati essere pari al 3% dei pazienti con un intervallo medio di 42,5 mesi dal momento del trapianto.
Dei 43 pazienti che hanno sviluppato neoplasie, 41 seguivano una terapia a base di inibitori della calcineurina, 2 erano invece pazienti trattati con everolimus.
Nello studio i fattori di rischio per lo sviluppo di tumori dopo trapianto sono risultati principalmente:
a. l'eta' al momento del trapianto, con rischio maggiore per i pazienti con eta'>_ 52,5 anni. b. lo stato EBV negativo al momento del trapianto.
c.il tipo di immunosoppressione usata, con rischio maggiore per i pazienti trattati con inibitori della calcineurina rispetto a quelli trattati con everolimus.
d. la dose di immunosoppressore, con rischio maggiore per i pazienti con elevata esposizione a CNI, in particolare ciclosporina con dose >_221,9 ng/ml/mese o tacrolimus con dose >_ 7,1 ng/ml/mese. Nella nostra casistica il tumore della pelle rappresenta il piu' comune tumore de novo (12 casi), ed e' in linea con i recenti report della letteratura, seguito dalla malattia linfoproliferativa post-trapianto (8 casi).
Degna di nota anche l'alta proporzione di tumori dell'apparato digerente (4 colon, 2 stomaco, 2 esofago, 2 pancreas, 1 vie biliari).
Lo studio presenta dei limiti riguardanti: -l'analisi retrospettiva
-i protocolli istituzionali cambiati col tempo: • agenti usati (ciclosporina versus tacrolimus)
• trattamento del rigetto del trapianto (anti-CD3 versus steroidi versus aumento della dose di CNI)
• maggiore uso di terapia di induzione (anti-CD25) nel recente passato
• maggiore focalizzazione sulle complicanze extraepatiche e sulla qualita' della vita -follow-up dei pazienti trattati con everolimus piu' breve rispetto ai pazienti trattati con CNI
-le politiche di screening per il cancro, di sorveglianza e prevenzione (per esempio la protezione solare, cessazione del fumo etc) implementate nel corso del tempo.
3.5
Conclusioni
Nella nostra esperienza, l'uso di everolimus, la maggiore esposizione a CNI, l'eta' avanzata al trapianto, e lo stato EBV negativo erano fattori di rischio indipendenti per neoplasie de novo dopo trapianto.
Le strategie di protezione per il cancro impongono una combinazione di iniziative quantitative (riduzione dell'esposizione a CNI) e qualitative (inibitori mTOR), soprattutto per i pazienti a rischio piu' elevato (anziani, EBV negativi).
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RINGRAZIAMENTI
Desidero ringraziare il Prof. Filipponi , relatore di questa tesi, per la disponibilità e cortesia dimostratemi e il Dott. De Simone per la collaborazione ed i suggerimenti che hanno contribuito alla stesura di questo lavoro.