POGOSTOST IN PRISTOP K ZDRAVLJENJU FOLIKULARNEGA LIMFOMA (FL), LIMFOMA PLAŠČNIH CELIC (LPC) IN LIMFOMA OBROBNIH CELIC (LMC) V UKC MARIBOR

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1 POGOSTOST IN PRISTOP K ZDRAVLJENJU FOLIKULARNEGA LIMFOMA (FL), LIMFOMA PLAŠČNIH CELIC (LPC) IN LIMFOMA OBROBNIH CELIC (LMC) V UKC MARIBOR TATJANA GRMEK ZEMLJIČ

2 NHL Incidenca NHL 3,7-15/ prebivalcev Narašča a ekspotencialno s starostjo, vrh obolevnosti pri 70. letih (ZDA let) 5% vseh novotvorb pri moških in 4% pri ženskah V Sloveniji okrog 250 novoodkritih bolnikov letno

3 Bolniki z limfomom obravnavani na hematološken oddelku v Mariboru v letih

4 Pristop k bolniku Potrditev limfoma Klasifikacija limfoma Klinični stadij bolezni Napovedni index

5 Obravnava bolnika Tipljivo povečane bezgavke ali vranica S slikovnimi preiskavami ugotovljene povečane bezgavke in/ali vranica B simptomi(20%):nepojasnjena temperatura, hujšanje, nočno znojenje Dispneja, utrujenost, bolečine v kosteh, disfagije, bolečine v trebuhu, zlateničnost... nost...

6 Diagnostični ni postopek - potrditev limfoma Anamneza, klinični pregled Citološka punkcija? Histološki pregled v celoti odstranjene begavke (vsaka več kot 4.tedne povečana bezgavka zahteva histološki pregled z imunocitokemičnimi nimi barvanji in genetske preiskave po FISH in/ali PCR)

7 Klasifikacija B-celiB celičnih limfomov po SZO Nezreli limfomi B: limfoblastni limfomb/levkemija Periferni limfomi B: KLL B/drobnocelični ni limfocitni limfom Prolimfocitna levkemija B Limfoplazmocitodni limfom Dlakastocelična levkemija Ekstranodalni limfom marginalne cone/maltom Splenični limfom marginalne cone z/brez vilusnih limfocitov Nodalni limfom marginalne cone z/brez monocitoidnih celic Pazmocitom, Folikularni limfom Limfom plaščnih celic, Difuzni velikocelični limfom B, Burkittov limfom/levkemija

8 Shema razvoja in diferencijacije B celic

9 Shema prvotnih celic in genetske spremembe v razvoju B celičnih limfomov

10 Limfomi FL VCBC Komb.L DCL PCL Per. TC Malt/LMC Med.VC Anapl.TC Limfobl. LMC n. Limfoplas. Burkitt.L ostali

11 Obravnavani po vrsti limfoma v letih na hematološkem oddelku v Mariboru FL LMC PCL VCBC MALT LPlc Tcel Hodg

12 Dodatne preiskave potrebne za določitev kliničnega nega stadija bolezni in napovednega indeksa Laboratorijske preiskave: : KKS, diferencijalna bela krvna slika, retikulociti, testi koagulacije(čas as krvavitve,aptt), Coombsov test, testi za oceno delovanja ledvic in jeter, LDH, imunoelektroforeza seruma in urina, kvantitativna določitev imunoglobulinov, beta2 mikroglobulin, serologija na EBV, CMV, HBV, HCV, HIV, toxoplazmo, imunofenotipizacija periferne krvi Pregled kostnega mozga z imunofenotipizacijo, citogenetiko (pozitiven izvid brez bezgavk ni dovolj za diagnozo)

13 Dodatne peiskave... Slikovne preiskave: Rentgenogram/CT prsnih organov, CT trebuha UZ vratu, trebuha FDG-PET Endoskopske preiskave (glede na lokalizacijo in tip limfoma)

14 Razširjenost limfoma Opredelitev kliničnega nega stadij bolezni Ann Arbor Ocena bolnikovega splošnega stanja (SZO - ECOG)

15 Napovedni indeks IPI Starost več 60 let Stadij III ali IV Več kot 1 najdba izven bezgavk LDH nad normalo ECOG več kot 1 FLIPI IPI Hb manj kot 120g/l Več kot 5 obolelih mest

16 FLIPI napoved Št. faktorjev Bolniki (%) 5-let. Prež.(%) 10-let prež.. (%) dobra srednja slaba Več kot

17 Dodatni napovedni dejavniki Beta 2 mikroglobulin genetske spremembe molekularne spremembe tveganje za transformacijo vzporedne bolezni odločitev bolnika

18 Slovenska priporočila ila za zdravljenje FL gradus I,II Mlajši i od 60 let 8x R-CHOPR Delna remisija visokodozna KT(VDKT)( HD Endoxana in TBI), purging s rituximabom,če izpolnjujejo kriterije ali RT ostanka, če e kriterijev za VDKT ne izpolnjujejo Popolna remisija - spremljanje, ponovitev R-FC R ali VDKT Klorambucil, COP ali R-CHOP, R če e se bolnik za visokodozno KT ne odloči

19 ila... Slovenska priporočila Starejši i od 60.let, stadij III, IV Klorambucil, COP, če e ni odgovora R-CHOPR Bolniki v stadiju I, II operacija ali/in RT Pogoj za VDKT:ostanek manj kot 2-4cm 2 bezgavk, manj kot 20% infiltracija KM po 8 x R-R CHOP Ostanek po VDKT RT Konsolidacija 8 x R

20 Zdravljenje FL v Mariboru zdravljenje začetno ponovitev vzdrževal. opazovanje 2 COP COP, RT 2 1 CHOP R CHOP 2 5 FMD 1 FCD 5 RFC 2 R, IFN 3

21 1,2 Prezivetje bolnikov FL Complete Censored 1,1 Cumulative Proportion Surviving 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0, cas prezivetja (mes)

22 Zdravljenje LMC priporočila ila Stadij III in IV klorambucil, COP, R-R CHOP pri nezadostnem odgovoru Stadij I, II operacija in/ali RT

23 Zdravljenje LMC v Mariboru začetno opazovanje 1 1 COP 5 COP, OP 2 CHOP 1 1 CHOP, OP 1 R-CHOP 1 ponovitev

24 Zdravljenje PCL Posebnosti: pogosta lokalizacija izven bezgavk (60% kostni mozeg, prebavila), značilna citogenetska sprememba t(11;14) agresiven potek (povprečno preživetje 3.leta)

25 Zdravljenje PCL priporočila ila Stadij III, IV mlajši i od 60. let 8xR-CHOP Delna remisija VDKT; purging R, če e ne izpolnjujejo pogojev za VDKT, RT ostanka Popolna remisija spremljanje Starejši i od 60 let klorambucil, COP, nezadosten odgovor R-CHOPR Stadij I,II OP in/ali RT

26 Priporočila ila zdraljenja PCL (nemška skupina za limfome)

27 Zdravljenje PL v Mariboru začetno klorambucil 1 COP 3 CHOP 1 FMD 1 R-CHOP 1 1 R-FC 1 R-Hyper- CVAD 1 ponovitev

28 Cumulative Proportion Surviving 1,2 1,1 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0,1-0,2 Prezivetje bolnikov z FL, LMC, PCL Complete Censored cas prezivetja (mes)

29 Zaključek Zdravljeni po priporočilih ilih do pred 3.leti, ko je uporaba bioloških zdravil omejena na OI Obravnava in načrt zdravljenja je individualen glede na vzporedne bolezni Sledenje bolnikov poteka ves čas v hematološki ambulanti Pomanjkljivosti pri obravnavi nimamo izkušenega patologa, molekularnga laboratorija

30 zaključek Kdo v Sloveniji naj zdravi bolnike z limfomi (klinični onkolog, hematolog)? opravi obravnavo bolnika? zdravi zaplete?

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