ࡱ> `<bjbj.*8p,,,,,,,@$)$)$)$)Dh)@_@*......</ c^e^e^e^e^e^e^$Z`hb^,0..00^,,..^_XXX0l,.,.c^X0c^XX [,,3[.4*  v+$)Ol#[W[ t_0_+[ceWc3[c,3[$"/0R/"Xt//"/"/"/^^X "/"/"/_0000@@@$$)@@@$)@@@,,,,,, Lije enje leukemije vlasastih stanica kladribinom Igor Aurer, Zdravko Mitrovi, Jasminka Kova evi-Metelko, Ivo Radman, Drago Batini, Jasminka Jaki-Razumovi, Marin Nola, Sandra Baai-Kinda, Silva Zupan i-`alek, Boris Labar Sa~etak Leukemija vlasatih stanica (triholeukemija) je kroni na B-limfocitna leukemija karakterizirana klonalnom proliferacijom vlasastih stanica. Terapija izbora su purinski analozi, u prvom redu kladribin. Lije ili smo trideset bolesnika kontinuiranom infuzijom kladribina kroz 7 dana u dozi od 0.1mg/kg dnevno ili dvosatnom infuzijom kroz 5 uzastopnih dana u dnevnoj dozi od 0.14mg/kg. Remisiju je postiglo 90% bolesnika. Nakon medijana praenja od 44 mjeseca pre~ivljavanje je 93%, a prosje no trajanje odgovora preko 6 godina. Dva bolesnika nisu reagirala na terapiju, a jedna bolesnica je umrla od infekcije kratko nakon terapije. Nuspojave su naj eae bile posljedica hematoloake toksi nosti, neutropeni ni febrilitet zabilje~en je kod 23% bolesnika, dok je 20% bolesnika je zahtijevalo transfuzije eritrocita i trombocita. Naai rezultati pokazuju da je kladribin siguran i u inkovit u lije enju leukemije vlasastih stanica. Nije bilo zna ajnijih razlika u toksi nosti i djelotvornosti izmeu sedmodnevne kontinuirane i petodnevne intermitentne primjene lijeka. Klju ne rije i: triholeukemija, lije enje, prognoza; kladribin Cladribine in the treatment of hairy cell leukemia Abstract Hairy cell leukemia is a chronic B-cell lymphoproliferative disorder characterized by clonal proliferation of hairy cells. Treatment of choice are purine analogues, particularly cladribine. We treated thirty patients with cladribine either by continuous 7-day infusion at a daily dose of 0.1mg/kg or by 2-h infusion for 5 consecutive days at a daily dose of 0.14mg/kg. Remission was achieved in 90% of the patients. After a median follow-up of 44 months overall survival is 93% and time to treatment failure more than 6 years. Two patients did not respond, one patient died of infection shortly after the treatment. Side-effects resulted mainly from hematological toxicity, 23% of the patients had neutropenic fever while 20% required platelets or packed red cell transfusions. Our results show that cladribine is safe and effective in the treatment of hairy cell leukemia. There were no significant differences in toxicity and response between 7-day continuous infusion and 5-day intermittent infusions of the drug. Descriptors: hairy cell leukemia, therpay, prognosis; cladribine Uvod Leukemija vlasastih stanica (triholeukemija, hairy cell leukemija) je indolentna leukemija B-limfocitne loze. Karakterizirana je klonalnom proliferacijom malih stanica s obilnom citoplazmom i nepravilnim citoplazmatskim izdancima poput vlasi (trihociti). Osim biljega B loze tumorske stanice stanice izra~avaju CD11c, CD25, FMC7 i CD103 dok su CD5, CD10 i CD23 negativni.1? Citokemijski se u njima mo~e dokazati kisela fosfataza koje je rezistentna na inhibiciju tartaratom (tartarat resistentna kisela fosfataza  TRAP). Tumorske stanice se mogu nai u krvi, koatanoj sr~i, jetri i slezeni. Bolesnici su obi no srednje ili starije ~ivotne dobi, a lije niku se javljaju zbog komplikacija pancitopenije ili splenomegalije. Triholeukemija ne reagira dobro na kemoterapiju uobi ajenu za druge indolentne limfoproliferativne bolesti. Do prije 20 godina je terapija izbora bila splenektomija, potom interferon alfa, da bi u zadnjih petnaestak godina to postali analozi purina poput pentostatina i kladribina. Kladribin (2-klorodeoksiadenozin, 2-CdA) je analog deoksiadenozina vrlo djelotvoran u lije enju triholeukemije. Jednim ciklusom terapije posti~e se povoljan odgovor u gotovo 100% bolesnika, od ega su, ovisno o kriterijima, od 50-95% kompletne remisije.2-11 Ponovno lije enje je u inkovito i u bolesnika koji do~ive relaps. Kladribin se naj eae primjenjuje kroz 7 dana u kontinuiranoj intravenskoj infuziji u dozi od 0.09mg/kg ili 0.1mg/kg.2-7 Takav na in primjene zahtijeva hospitalizaciju bolesnika. Ambulantno se kladribin mo~e davati u dozi od 0.14mg/kg dnevno u dvosatnoj infuziji 5 dana uzastopno8,9, jednom tjedno kroz 6 tjedana10 ili supkutano11. Kladribin se u naaoj ustanovi rutinski primjenjuje zadnjih 10 godina u terapiji bolesnika s leukemijom vlasastih stanica. U ovom radu prikazujemo rezultate takvog lije enja. Bolesnici i metode Bolesnici Retrospektivno je identificirano 30 bolesnika koji su u razdoblju izmeu listopada 1996. i kolovoza 2005. u KBC-u Zagreb primali kladribin zbog leukemije vlasastih stanica. Za 18 je to bila prva linija terapije, dok ih je 12 prethodno lije eno drugim metodama. Zna ajke bolesnika u vrijeme zapo injanja terapije kladribinom prikazane su u tablici 1. Veina ih je bila citopeni na, samo tri su imala povean broj leukocita na ra un brojnih vlasastih stanica u periferiji. Dijagnoza Dijagnoza leukemije vlasastih stanica postavljena je na temelju tipi nog izgleda stanica u aspiratu ili bioptatu koatane sr~i, pozitivne TRAP reakcije i karakteristi nog imunofenotipa tumorskih stanica. Lije enje Glavni kriterij za zapo injanje terapije bila je citopenija: koncentracija hemoglobina (Hb) manja od 100g/L ili broj neutrofila (ANC) manji od 1.0x109/L ili broj trombocita (Trc) manji od 100x109/L, odnosno recidivirajue infekcije. Kod 18 bolesnika kladribin je primijenjen u bolnici kao kontinuirana infuzija u dozi od 0.1mg/kg dnevno kroz 7 dana. Preostalih 12 je primilo lijek ambulantno u dozi od 0.14mg/kg dnevno u dvosatnoj infuziji kroz 5 uzastopnih dana. Odluka o na inu primjene kladribina donoaena je ovisno o stupnju pancitopenije, mogunosti bolesnika da svakodnevno dolazi na lije enje i naaoj mogunosti da bolesnika hospitaliziramo. U hospitaliziranih bolesnika krvna slika je do oporavka praena svakodnevno, a u izvanbolni kih jednom do dva puta tjedno. Svi bolesnici su, dok su bili neutropeni ni, primali profilakti ku peroralnu antimikrobnu terapiju (naj eae ciprofloksacin), transfuzije krvnih pripravaka prema klini koj slici i vrijednostima krvne slike, a u slu aju vruice lije eni su u bolnici empirijski antibioticima airokog spektra. Promatrani ishodi Analizirali smo toksi nost lije enja, potrebu za transfuzijama, pojavu infekcija, vrijeme potrebno za normalizaciju krvne slike, odgovor na lije enje, pre~ivljavanje i pojavu sekundarnih tumora. Toksi nost lije enja smo ocjenjivali prema uobi ajenim kriterijima.12 Teakim nuspojavama smo smatrali one stupnja 3-5. Vruice preko 38,5 C nepoznatog uzroka smo ubrojili u infekcije. Vrijeme potrebno za normalizaciju krvne slike je razdoblje od po etka lije enja do porasta Hb > 120g/L, ANC > 1,5x109/L i Trc > 100 x109/L. Relaps je definiran kao ponovna pojava citopenije nakon postignute remisije uz prisutnost vlasastih stanica u koatanoj sr~i. Statisti ka analiza Rezultati su opisani deskriptivnim statisti kim metodama. Krivulje trajanja najboljeg odgovora na injene su prema Kaplan-Meierovoj metodi.13 Za meusobnu usporedbu promatranih skupina koriaten je log-rank test.14 Rezultati Toksi nost lije enja Veina bolesnika je u roku od dva mjeseca normalizirala krvnu sliku (tablica 2). Ambulatno lije eni bolesnici br~e su oporavili krvnu sliku od onih lije enih bolni ki (7 naprema 10 tjedana), no potonji su na po etku lije enja imali ni~i Hb (117 naprema 99 g/l). `est bolesnika (20%) je nakon terapije kladribinom primilo transfuzije trombocita ili eritrocita. Sedam (23%) ih je hospitalizirano ili im je produljena hospitalizacija zbog infekcije. Uzrok i mjesto infekcije je otkriveno u njih etvero. Jedna bolesnica je umrla 17 dana od po etka terapije od tuberkuloznog meningitisa, u drugoga je doalo do pogoraanja otprije prisutne ko~ne infekcije, u treeg do egzacerbacije takoer od ranije prisutnog plunog aspergiloma, dok je etvrti bolesnik razvio gljivi nu pneumoniju. Kod ostalih bolesnika nije naen uzro nik odnosno izvor infekcije. U dva bolesnika lije ena kontinuiranom infuzijom kladribina se javila mu nina i povraanje, a jedna bolesnica je 2 mjeseca nakon terapije razvila brzu fibrilaciju atrija i dekompenzaciju srca. Bolesnici kojima je ovo bila prva linija terapije su lije enje podnijeli jednako dobro kao i ve ranije lije eni. Odgovor na lije enje Prema uobi ajenim kriterijima, povoljnim odgovorom na lije enje triholeukemije se smatra postizanje kompletne (KR) ili parcijalne remisije (PR). PR je definirana kao normalizacija krvne slike, dok je za KR potreban i nestanak vlasastih stanica iz koatane sr~i te smanjenje slezene na normalnu veli inu3-8. Budui da se ni bolesnike u PR niti one u KR ne lije i do pojave relapsa, mi nismo nakon lije enja rutinski ponavljali analize koatane sr~i. Stoga nismo u mogunosti razlikovati KR i PR. U trenutku pisanja rada jedan bolesnik je terapiju dobio pred manje od 3 mjeseca pa se u inak lije enja joa ne mo~e procijeniti. Remisiju je postiglo 26 od 29 bolesnika, odnosno 90%. Jedna bolesnica je umrla od infekcije ubrzo nakon po etka lije enja, a dva su bila refraktorna na terapiju. U oba je tri mjeseca nakon primjene kladribina perzistirala pancitopenija i leukemijska infiltracija koatane sr~i. Jedan je uaao u remisiju na rituksimab, a drugi ~ivi s aktivnom boleau bez terapije godinu dana. Nakon medijana praenja od 44 mjeseca pre~ivljavanje je 93%, a prosje no trajanje odgovora preko 6 godina. Do relapsa je doalo u 6 bolesnika (21%) (slika 1). Tri su ponovno lije ena, sva tri kladribinom. Dva su ponovno postigla remisiju, a u treega se nakon 4 mjeseca joa nije oporavila krvna slika. Nije bilo razlike u u estalosti postizanja remisije i trajanju najboljeg odgovora izmeu skupine bolesnika kojima ovo nije prva linija lije enja i onih koji do sada nisu lije eni (log rank 2.33, p=0.12). Sekundarni tumori Sekundarni zloudni tumori javili su se u dva bolesnika. U jednog je 6 godina nakon primjene kladribina dijagnosticiran metastatski karcinom prostate. Druga bolesnica je operirana zbog bazeocelularnog karcinoma noge. Rasprava Naai rezultati odgovaraju rezultatima drugih studija provedenih na znatno veem broju bolesnika i s duljim praenjem. Ukupno 26 od 29 bolesnika (90%) je postiglo remisiju, a stopa relapsa nakon medijana praenja od 44 mjeseca iznosi 21%. U istra~ivanju Savena i sur. na 358 bolesnika nakon jednog ciklusa kladribina primjenjenog u sedmodnevnoj kontinuiranoj infuziji (0.1mg/kg) stopa kompletnih remisija iznosi 91% uz 7% parcijalnih remisija, te stopu relapsa od 26%, nakon praenja od blizu 6 godina.4 Nedavno je objavljena studija na 86 bolesnika s medijanom praenja od 9.7 godina, gdje je jednim ciklusom kladribina primijenjenog u 7-dnevnoj kontinuiranoj infuziji postignut odgovor u 100% bolesnika (79% KR, 21%PR), stopa relapsa je iznosila 36%.5 Ipak, u najveoj, multicentri noj studiji u koju je uklju eno 979 bolesnika, stopa kompletnih remisija je neato ni~a (50% KR i 37% PR).2 Iako je naaa studija provedena na nevelikom broju bolesnika bez mogunosti razlikovanja KR i PR, ini se da su rezultati postignuti trajnom infuzijom kladribina sli ni onima postignutim intermitentnim kraim infuzijama. Sli ne rezultate imali su i drugi autori koji su usporeivali ova dva oblika lije enja,8,9 s tim da su Robak i sur. u nerandomiziranoj studiji zamijetili manju u estalost infekcija u ambulantno lije enih bolesnika8. U sve tri najvee studije, bolesnici s po etnim ni~im hemoglobinom i viaim brojem leukocita su imali krae trajanje najboljeg odgovora.2-4 Takoer, i neki drugi initelji poput starije dobi2, loaeg opeg stanja2, prethodne terapije pentostatinom2 splenomegalije4 i kraeg trajanja bolesti3 su u pojedinim serijama negativno utjecali na rezultate lije enja. U naaoj skupini dob, vrijednosti krvne slike na po etku, kao niti vrsta prethodnog lije enja nisu zna ajno utjecali na ishod terapije kladribinom, vjerojatno zbog razmjerno malog broja bolesnika. Naj eai terapijski pristup u bolesnika u relapsu je ponovno lije enje kladribinom. Alternative su pentostatin, a u novije vrijeme i rituksimab. Ponovnim lije enjem kladribinom posti~e se remisija u oko 90% bolesnika, uz neato loaiji omjer KR i PR u odnosu na prvi ciklus (50- 65% KR i 20-30%PR).2-6 Svega tri naaa bolesnika su primila ponovnu terapiju kladribinom, u dvojice je praenje krae od 5 mjeseci. Jedan od dva naaa bolesnika, koji nisu reagirali na kladribin, postigao je remisiju rituksimabom. Rituksimab je monoklonsko protutijelo usmjereno protiv CD20 antigena koje se mo~e koristiti i u lije enju triholeukemije, budui da su vlasaste stanice CD20 pozitivne. Odgovor se posti~e u 50- 80% bolesnika.15,16 Ti rezultati su slabiji od onih koji se posti~u kladribinom. No, uzevai u obzir vrlo nisku toksi nost, rituksimab bi se mogao koristiti kao terapija odr~avanja za eradikaciju minimalne ostatne bolesti, u pancitopeni nih bolesnika loaeg opeg stanja te u kombinaciji s kladribinom. Hematoloaka toksi nost lije enja triholeukemije kladribinom je prihvatljiva, posebice uzimajui u obzir da su ti bolesnici obi no citopeni ni pri dijagnozi. Svega 20% ih je trebalo transfuzije trombocita ili eritrocita, listom oni koji su na po etku bili izrazito anemi ni, odnosno trombocitopeni ni. Od sedam bolesnika koji su razvili neutropeni ni febrilitet, samo kod troje je dokazan uzrok infekcije. To je u skladu s drugim studijama gdje takoer kod veine bolesnika nije dokazan uzrok febriliteta.4-6 Obzirom na uglavnom nejasan uzrok febriliteta, korist od profilakti ke primjene antimikrobnih lijekova je dvojbena, a profilakti ka primjena granulocitnog imbenika rasta ne smanjuje u estalost neutropeni nog febriliteta.17 Prema naaim rezultatima osnovni imbenik rizika za pojavu infekcije je postojanje potencijalnog infektivnog ~ariata na po etku. U dva naaa bolesnika javile su se sekundarne neoplazme. Obzirom da su bolesnici prosje no praeni manje od 4 godine, za o ekivati je da e pojavnost sekundarnih tumora rasti. Nekoliko je istra~ivanja na velikom broju bolesnika s leukemijom vlasatih stanica analiziralo u estalost sekundranih neoplazmi.18,19 Naena je poveana u estalost posebice solidnih tumora (prostata, ko~ni tumori) u odnosu na zdravu populaciju. ini se da ta pojava nije povezana s odreenom vrstom terapije, nego je posljedica biologije triholeukemije. Zaklju no, mo~emo rei da je kladribin djelotvoran, siguran i dobro podnoaljiv lijek za lije enje leukemije vlasatih stanica. Hematoloaka toksi nost je vea u bolesnika koji po inju lije enje izrazito citopeni ni. Naj eae nuspojave su infekcije, u prvom redu neutropeni ni febrilitet. Potrebno je dugo praenje bolesnika obzirom na mogunost kasnog relapsa, no i tada se opet mo~e uspjeano primijeniti kladribin. Nema zna ajnije razlike u pogledu toksi nosti i djelotvornosti izmeu sedmodnevne kontinuirane i petodnevne intermitentne primjene kladribina. Tablica 1. Zna ajke bolesnika s leukemijom vlasastih stanica lije enih kladribinom Table 1. Characteristics of patients with hairy cell leukemia treated with cladribine Ukupno / TotalKratka infuzija /Short infusionTrajndf *FJ 4t!|!""0$6$r$v$$$%*&,,:-<-:6>6 882848v:z:; ;;B;FGFRpR\V^VPXRXfYhY[١٘٘٘٘٘٘٘٘٘٘٘٘٘٘٘٘hquyCJH*aJ *hquy5CJH*aJhquy5CJaJmH sH hquyCJaJmH sH hHzhquyCJaJhHzCJaJhquyCJaJhquy5CJaJ hHzCJ hquyCJhquy5CJaJ<df (* 24ddh$dha$<b$%%%%&&&*&,&@&))*+++44d`d44.46989`9;;;;;;;;; ;";$;&;(;*;@;B;l;tDvDD`PbPd`dbPP>R@RBRDRFRHRJRLRNRPRRRTRVRXRZR\RpRrRlY\(aZdios$&((覡 *hquyhquy hquy6 hHzCJ hquyCJH* *hquyCJhquyCJaJ hquy5CJU hquyCJ] hquy6CJ hquyCJ hquyCJhquyCJaJhquyCJH*aJ<x@xxyyyyy@ $dh$Ifa$ dh$Ifhdh`hdh a infuzija/ Continuous infusionBroj bolesnika (No. of patients)301218Dob (godine) / Age (years) medijan (raspon) / median (range)52 (36-76)57 (36-76)51 (38-68)Spol M/} / Sex M/F 20/108/412/6Prethodna terapija / Previous therapy interferon alfa interferon alfa + pentostatin interferon alfa + splenektomija / splenectomy pentostatin rituksimab / rituximab bez terapije / no treatment  6 2 2 1 1 18 2 0 1 0 0 9 4 2 1 1 1 9Vrijeme od dijagnoze do kladribina (mj) / Time from diagnosis to cladribine (mo) medijan (raspon) / median (range) 5 (0-171) 18 (0-171) 3 (1-168)Po etne vrijednosti krvne slike / Blood counts at baseline Granulociti / ANC (x109/L) medijan (raspon) / median (range)0,83 (0,03-2,81)0,83 (0,17  2,61)0,79 (0,03-2,81) Hemoglobin (g/L) medijan (raspon) / median (range) 114 (64-157)117 (89-157)99 (64-144) Trombociti / Platelets (x109/L) Medijan (raspon) / median (range) 79 (17-175)75 (32-139)83 (17-175) Tablica 2. Odgovor na lije enje i u estalost ozbiljnih nuspojava Table 2. Response to treatment and incidence of serious side-effects Svi/AllKratka infuzija / Short infusionTrajna infuzija / Continuous infusionNeutropeni ni febrilitet / Neutropenic fever734Primili transfuzije / Transfused624Mu nina /Nausea202Smrtni ishod/ Death 101Refraktornost na terapiju / Refractoriness to therapy211Relaps/ Relapse624Du~ina praenja (mj) / Duration of follow-up (mo) medijan (raspon) / median (range) 44 (1-103)44 (15-82)39 (1-103) Slika 1. Trajanje najboljeg odgovora nakon terapije kladribinom Picture 1. Time to treament failure after cladribine treatment  EMBED Excel.Chart.8 \s  Literatura ne znam koju referencu ste uzeli, Williams? Ne klasifikacija SZO. Pitaj citologe.  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term=%22Cheson+BD%22%5BAuthor%5D" \o "Click to search for citations by this author." 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( ( " F4(EMF+*@$??FEMF+@ ObjInfo WorkbookSummaryInformation( DocumentSummaryInformation80      !"#0%&'()*+,-./12345689:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefgh \p igor.aurer Ba= "/ = o<X@"1JArial1JArial1JArial1JArial1JArial1JArial1>JArial1>JArial1>JArial1>JArial1>JArial1JArial1JArial1JArial1JArial1JArial1JArial1JArial#,##0\ "kn";\-#,##0\ "kn"##,##0\ "kn";[Red]\-#,##0\ "kn"$#,##0.00\ "kn";\-#,##0.00\ "kn")$#,##0.00\ "kn";[Red]\-#,##0.00\ "kn">*9_-* #,##0\ "kn"_-;\-* #,##0\ "kn"_-;_-* "-"\ "kn"_-;_-@_->)9_-* #,##0\ _k_n_-;\-* #,##0\ _k_n_-;_-* "-"\ _k_n_-;_-@_-F,A_-* #,##0.00\ "kn"_-;\-* #,##0.00\ "kn"_-;_-* "-"??\ "kn"_-;_-@_-F+A_-* #,##0.00\ _k_n_-;\-* #,##0.00\ _k_n_-;_-* "-"??\ _k_n_-;_-@_-"kn"\ #,##0;\-"kn"\ #,##0#"kn"\ #,##0;[Red]\-"kn"\ #,##0$"kn"\ #,##0.00;\-"kn"\ #,##0.00)$"kn"\ #,##0.00;[Red]\-"kn"\ #,##0.00>9_-"kn"\ * #,##0_-;\-"kn"\ * #,##0_-;_-"kn"\ * "-"_-;_-@_-,'_-* #,##0_-;\-* #,##0_-;_-* "-"_-;_-@_-FA_-"kn"\ * #,##0.00_-;\-"kn"\ * #,##0.00_-;_-"kn"\ * "-"??_-;_-@_-4/_-* #,##0.00_-;\-* #,##0.00_-;_-* "-"??_-;_-@_-                 , * + )                            `:- Grafikon1 ?List1 GList2 p{List3"ZR3 A@@   z$prezimeimebroj DBHprethodna terapijalije enje (bolni ko= 0 DBH=1)spol (z=0, m=1)!godine (u vrijeme primjene 2-CDA)&potreba za transfuzijama (Ne= 0, Da=1)zadnja kontrolakomentar`oiKaticaINFinfekcije (NE= 0, DA= 1)Zvrijeme do postizanja stabilne vrijednosti krvne slike (Hb>100, T >100, gran > 1,5) - danitrajanje najboljeg odgovora(mj) 6mj.04 -KRLisni Borka+vrijeme od dijagnoze do primjene (2CDA) -mjnuspojave (osim hematoloakih)mu nina 11mj.04 - KR21.03. treba do na kontroluBeaoviLokmanINF, pentostatinKnjazBarica7primala 3 dana G-CSF nakon th.(zbog blaaze leukopenije)"prednison, pentostatin (3 ciklusa)8mj04-KR 11mj04-KR[primala GM-CSF 10 dana, E i T se oporavili nakon 11 dana, leukopenija potrajala nesto duljeLackoviFranjoINF splenektomiran 1/94HeroJelka 10mj04-KRVuletiDuakodugo 11mj04-PRfT oko 100, Leukociti vei od 0,5 ali manji od 1,5. Od 3mj.01 prati se bla~a citpenija (S.P. 3mj.03 PR) spol (z-m)#prethodna terapija (da (koja?) -NE):potreba za transfuzijama eritrocita (da (koliko puta?)-ne):infekcije nakon kladribina (NE, DA-lokalizacija,uzrocnik):potreba za transfuzijama trombocita (da (koliko puta?)-ne)sekundarne neoplazme* ponovna terapija ne - da (cime? Odgovor?) relaps da-ne: ponovna pojava palpabilne slezene ili pada u krvnoj slici (Nakon koliko mj.), citoloaka punkcija-koliko vlasastih stanicaIX)lije enje kladribinom (bolni ko-0, DBH=1)LACKOVI FRANJO prezime i imemInterferon u 2 navrata?ne-vrijeme od Kladribina do zadnje kontrole (mj)!nalazi prije th. (Hb, L -gra, Tr)JNeupogen(G-CSF zbog prolongirane granulocitopenije (da - (koliko dana)-ne)Splenektomija (DA kada? -NE)1mj94 Vuleti Duako!Hb116, L 2.5 (seg16,neseg6), T 95=najnize vrijednosti nakon th. Hb, L,T - gradus prema NCI-CTC5mj05da,da, pojava bla~e citopenije nakon 54 mjeseca"0 (10mg u24h infuziji kroz 4 dana)odgovor)PR (norm. KKs uz postojanje bolesti u KS) Lisni BorkazHb107, L 2.2 (seg21%), T 60KR3mj05Beaovi LokmanINF, pentostatin, opet INFHb139, L 3,2 (seg 57%), T 147 0 (7mj98)L 2,5 (seg 69), ostalo norm.8mj04*hb111, L 1.8 (seg izmeu 0,5 i 1,0), T85, Bukvi Stjepan6mj05hb91; L 3.3 (24%) Tr 1351 - 6,3mg u 2h inf. Kroz 5 danaHb83, L 1,9 8seg34%) Tr11, 1x-da (Ca prostate uz suspektne meta na kostima) Bo~ac RomanoHb94 L 0,9 tr 17da, opet kladribin 5mj05 BO}AC ROMANO `OI KATICAHb 118 L 2.7 (seg31%) T 1391-6mj00 (5mg/2h)Hb107 L 1.6 (seg 63%) T145da 3dana KNJAZ BARICA*Hb132 L 2.7 (24%, triholeukociti 6%) T 1031- 6mj01 (0.09mg/kg)Hb91 L 1.0 (nema difa) T 86)da - 2 tjedna(+profilakti ki antibiotici)11mj04 Peri Milanne? SOMUN DAVORH 117 L 14.3 (seg 18) T 67Hb119 T 58 L 0,6febrilitet do 38Vlahovi Mirjana?Hb64 L 15.3 (neseg2, seg4,ostlo limfociti i vlasaste st.), T 371-2076/04 4mj04(7 dana)dNR- povla enje slezene, djelomi ni oporavak E i T, prolongirana leukopenija, prisutnost bolesti u KSne - nije ni bilo remisije da-rituximab4mj05da (duze vrijeme - 5 mjeseci)AHMETOVI MLADEN%Hb89 L 2,2 (seg31,ly67,mo2,ebl1) T 461 -5x8.5g u inf.2h 6mj04Hb69 L 1.4 (seg41), T57 vjerojatno nefebrilna neutropenija 4439/04IVANKOVI IVICAHb90 L 1,1 (neseg1,seg14%) T 331-2mj01-nema podatakHb75, T29 L 0.3 vjerojatnoAnderlon Barbara+da INF - prekinut jer ga je tesko podnosila+Hb111, L3,4 (neseg10,seg34,ly54,mo1%) T 110 nepoznati0- 7dana 1mj00 251/0010mj04? Ne?ne BRI`AR }ELJKO2Hb108 L 3,7 (seg8) T 32 + izrazita splenomegalijada - kladribinHb139 L2.8 (neseg1, seg 17) t34Hb133 L 1.0 T85Vlaai LjudmilaHb75 L 3.2 (seg11) T 64 nepoznato/nepoznato (primila 2 trabsfuzije E prije 2CdA)) KOLI NEVENKA!Hb139 L2.3 (seg 54, neseg2) T 109 1 - 5mj98 Hero JelkaHb135 L 4.6 (seg40) T 1060- 8mj98 (7dana)0- 7 dana 5mj98trombocti iznad 100 Mikuska JosefHb 101 L 20.3 (seg2) tr 830- 7 dana 10mj98Hb 90 L 0.9 T78ne? 3mj99 Iz Osijeka Kubin FranjoWprimio kladribin u bolnici 10mj04 -6271/04, otpusten u toplice zbog Cvi i otada ga nema Brzica mladen!Hb 144 L 2.5 (neseg2, seg19) Tr ?1- 7 dana 10mj97 (0.1mg/kg)9mj02 Koaec IvanKprimao (nejasno kako i koliko od dg.) 97, postigao PR i dalje nema podatakaMaari Miroslav Hb 131 L 2,0 (seg59,neseg8) T 501- 9mj97 - 7 danahb 109 L 0.6 T 16912mj97 VUJI IVANHb90 L3.7 (seg 39) T 75 1- 12.05.04da ;nisu se oporavile do zadanih vrijednosti ni nakon 14mjeseci Bat Borivoj"Hb 104 L 4,2 (seg63, neseg2) T 175"KR (uz 2-3% triholeukocita u S.P.)0-4mj04 2772/04Kova i Marija/~ rituksimab 2xHb 96 L 3.3 (seg 85%) T141 0 29.3- 5.4.05Hb 98 L 5.68seg 80) T 19da (sepsa, TBC) pankreatitisumrladokazan BK u likvoru BA`I JOSIPSABLJI ALEKSANDAR $Hb141 L 16,1 (gra 16 triho 37%) T 73 1- 10mj01Hb 124 T68 L 0.99mj050 (2303/01) kroz 7 dana 4mj01&iz Zagreba je covjek, Labarov bolesnik29.8.Grbi Zvonimir%Hb 95 L 6,0 (neseg1, seg7, ly92) T 59hb 99 L 2,3(gra58) T100mu nina i slabosthb61 T iznad 200 L 0,4Hb 77 L 1.0 (15% seg) T 102da1x0 (5082/03 - 9mj03Hb98 L0,4 T norm.jaka mu nina uz povraanjeda 3x600Hb68 L0,4 T 48Hb 103 L 2.2 T 141Hb65 L0,6 (seg 50), T25da4x600cda (febrilna neutropenija) uz lokalni upalni proces na mjestu preegzistentne lezije (egzacerbacija)"Hb 131 L 3.1( seg 37,neseg1), T 87Hb84, L 0.2, T58, da2x - zbog epistakse0 (280/04, 495/04) 1mj04 0 - 5mj99 1 - 1mj017Hb dobar, T 141 L 2.4 (seg53, neseg5) - oskudni podaci? malo podatakaHb157 L 4.2 (seg62) T 135 JAK`I MARIJA 1 - 11mj013mj03 0- 3.5.05Hb dobarL 1.7 (seg 26) T<100Hb125 Tr 57 L 0,71nije jos dosegao kriterije oporavka - leukopenija31-DBH/ 0- 615/03 (1.1mg dnevno kroz 5 dana) - 2mj030 (5177/03) - 9mj03 0-23 5.mj0513tjMari evi MarijannoviHb116 L 1.3 (seg2) T29 Hb79 L0.2 Tr1310x300ugda 1xda (pluna mikoza) jos je rano4x500Slivak StjepanHb 130 L 2,0 (seg70) T 985mj97 kroz 7 danaHb 134 L1,5 (seg66) T 87da (Kladribin -amb) u2mj02SLIVAK STJEPANHb 120 L 2,6 8eo2,seg66) Tr111 DBH 2mj00Hb124 L0,9 (seg40%) T102da 2xnepoznato, viae od 6tj*suspektan relaps 2,5 - 5% trihocita u S.P.do reevaluacije, 7 do Mabthere pentostatin, prednisolon (1994)? NR[vrijeme do postizanja stabilne vrijednosti krvne slike (Hb>120, T >100, gran > 2,0) -tjedni neda, nakon 33mjdo zadnje kontroleda9mj02 - 59mj!da - 3mj05 - 47mj; pancitopenija trajanje najboljeg odgovora 1- 3mj99 10mgda 5mj05 -74mjda-63mj da-Kladribinda -egzacerbacija mikoze plue8mj05*da (febrilna neutropenija- hospitaliziran)0da (febrilitet, nije zahtijevao hospitalizaciju)@relaps dokazan u 6mj05 iako je godinu prije toga bio citopeni anda - imala baz<*aliom na kozi granulocitiYAmbulantni: Hb medijan 117 (89-157), ANC medijan 0,83 (0,17-2,61), T medijan 75 (32-139)Lbolnicki: Hb medijan 99 (64-144), ANC medijan 0,74 (0,03-2,81) T 87 (17-175)mj.ip)U injena sternalna 10mj05 - 45% trihocita* _ K  =/qHX G L   l `'qL:u !a!"[#a$2%|%=&G'(Z)\)(+  MBhp deskjet 5100 seriesskjet 51!@d߀ 4d,Be4 d EXCELArialHBeںں\\MEDICINS-70BC7C\hp deskjet 5100 series,LocalOnly,DrvConvert$*Kg`XX" d,,??3` c ` c ` ! /?3d23 M NM4 3Q :trajanje najboljeg odgovoraQ ; Q ; Q3_4E4D$% M3O&Q4$% M3O&Q4FA4cE 3Oai 3 bPP PZaajkR R R RR RV VѴMS S43*Y@4@#M4% uJ VM3ON$&Q "mjeseci/months '4% MZ3Og&Q *postotak/percentage'4523 M  43" 3_ M NM  MM<44S S4% M%3OQ'4S S 4e@@"@(@.@2@5@8@ ;@ >@ @@ B@ C@E@F@H@I@K@L@N@O@P@@Q@R@R@S@@T@U@eY@_B{ %W@_B{ %W@_B{ %W@_B{ %W@_B{ %W@_B{ %W@_B{ %W@_B{ %W@ _B{ %W@ _B{ %W@ ;tWU@ ;tWU@ ;tWU@;tWU@;tWU@PPT@PPT@x{IHR@x{IHR@PA@P@ MrpL@ MrpL@ MrpL@ MrpL@mAq[F@mAq[F@mAq[F@`7l[F@e> `7l   dMbP?_*+%"??U} m } } m                    @@P@  08@?(@H@     6"@I@@   :@,@     @N@? 0R@>@R@    `@Q@ 0@e@?T@D@   ! 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