ALL IC-BFM 2002 - მედპორტალი · blasturi ujredebis imunologia - mll leikemiis...

bavSvTa asakis mwvave limfoiduri leikemiissamkurnalo protokoli

ALL IC-BFM 2002

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bavSvTa asakis Mmwvave limfoiduri leikemia (mll)

epidemiologia: mwvave limfoiduri leikemia bavSvTa asakis yvelaze xSiri simsivnuri daavadebaa da mTliani pediatriuli simsivneebis mesameds Seadgens. daavadebis wliuri ricxvi, internacionaluri statistikuri monacemebiT, erT milion mosaxleobaze Seadgens 30 SemTxvevas. Aamerikis SeerTebul StatebSi yovelwliurad fiqsirdeba 2000 - 2500 axali SemTxveva, saqarveloSi zusti statistikuri monacemebi ucnobia, Cvens klinikas momarTavs 25 - 30 pacienti, magram binaze udiagnozod gardacvlil pacientTa an im pacientTa ricxvi, romlebic pirveladi diagnozisa da mkurnalobis mizniT miemgzavrebian sazRvargareTis qveynebSi, ucnobia.

rasobrivad mll ufro xSiria kavkasiur mosaxleobaSi vidre afrikul- amerikulSi. daavadebis piki bavSvebSi aris 2-5 weli. biWebSi ufro xSiria vidre gogonebSi, aRniSnuli gansxvaveba upiratesad vlindeba T ujredovani formebis dros.

pacientTa gadarCenis sixSire da sikvdilianoba: diagnostikuri meTodebis da risk faqtorebze asocirebulma mkurnalobis Tanamedrove protokolebma mwvave limfoiduri leikemiiT daavadebul bavSvTa gadarCenis mTliani sixSire 80%-mde gazarda, magram bolo statistikuri monacemebiT mkafiod vlindeba gadarCenis heteregenuroba da mxolod 30%-s Seadgens cudi prognozis mqone pacientTa jgufebSi. prognozuli faqtorebi TiTqmis msoflios yvela samecniero centrebis monacemebiT emyareba asaks, sqess, prednizolonze da remisiis induqciis sxvadasxva etapebze qimioTerapiaze pasuxs, inicialuri leikocitebis saerTo raodenobas da blastur ujredebSi qromosomul translokaciebs.

etiologia: miuxedavad imisa, rom daavadebis zogierTi SemTxveva asocirebulia Tandayolil genetikur sindromebTan, mwvave limfoiduri leikemiis gamomwvevi mizezi ucnobia. aseve mravali garemo faqtori (ionizaciuri radiacia, eleqtromagnituri velebi, alkoholis an nikotinis gamoyeneba) iqna gamokvleuli, rogorc potenciuri risk faqtori, magram arc erTma maTganma gamomwvevis xasiaTi erTmniSvnelovnad ar aCvena.

paTogenezi: Mmwvave limfoidur leikemias safuZvlad udevs limfoidur progenitalur ujredebSi momxdari genetikuri cvlilebebi maTi Semdgomi disregularuli proliferaciiTa da klonaluri eqspansiiT. transformirebuli limfoiduri ujredebi anu leikemiuri blastebi didi xnis ganmavlobaSi warmodgenili iyo, rogorc klonaluri eqspansia gamowveuli hemopoezuri ujredis blokirebiT diferencirebis romelime etapze.Bbolo samecnioro monacemebis safuZvelze es Teoria icvleba da gvTavazobs, rom leikemia warmoiSoba Rerovani ujredisgan, romelic Tavad gansazRvravs diferencirebuli ujredebis xasiaTs. Ees dakvirveba dagvexmareba mkurnalobis arsSi, rom mniSvnelovania ara mxolod diferencirebuli blastebis, aramed leikemiuri Rerovani ujredis eradikacia. swored aseTi gagebiT miiRweva pacientis gankurneba.

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mwvave limfoiduri leikemia momdinareobs Zvlis tvinidan, magram blasturi ujredebi sistematurad gvxvdebian sxva organoebSic: TimusSi, RviZlSi, elenTaSi, limfur kvanZebSi, saTesle parkebSi, centralur nervul sistemaSi. daavadebis prevencia: radgan ar aris dadgenili mll-is gamomwvevi mizezi, Sesabamisad ar arsebobs misi Tavidan acilebis profilaqtikuri RonisZiebebi.

klinikuri simptomebi: mll-iT daavadebuli pacientebi diagnozisas avlenen im niSnebsa da simptomebs, romlebic gamowveulia Zvlis tvinis infiltraciiT da eqstramedularuli daavadebiT. Sesabamisad, pacients aReniSneba Zvlis tvinis ukmarisoba anemiiT, trombocitopeniiT da neotropeniiT. klinikur monacemebSi yovelive es vlindeba sisustiT da sifermkrTaliT, peteqiebiT, sisxldeniT da cxelebiT. leikemiis eqstramedularuli gavrcela manifestirdeba limfadenopaTiiT da hepato-splenomegaliiT, osalgiebiT, sunTqvis ukmarisobiT. centraluri nervuli sistemis dazianebis SemTxvevaSi pacients aReniSneba Tavis tkivili, Rebineba da gulisreva, meningialuri niSnebi, leTargia; kranialuri nervebis (umetesad me-7 , me-3, me-4 da me-6 nervebis) CarTva vlindeba maTi pareziT. spinaluri da intrakranialuri masis SemTxvevebSi adgili aqvs nervebze kompresiiT gamoxatul simptomatikas.

testikularuli leikemia diagnozisas iSviaTia da, Tu adgili aqvs, vlindeba saTesle parkebis mtkivneulobiT da gadidebiT. diagnozi: anamnezis dadgenisa da fizikaluri gasinjvis Semdeg pacients utardeba Semdegi bazisuri laboratoriuli testebi:

sisxlis sruli analizi - hemoglobinis da formiani ujredebis raodenobrivi diferencirebis mizniT SesaZloa damTvleli manqanis gamoyeneba, magram limfoblastebis identificirebis da morfologiis dasadgenad aucileblad ikvleva gimzas wesiT SeRebili nacxebi. nacxebs swavlobs hematologi an specialisti paTomorfologi.

Zvlis tvinis aspiratis sruli morfologia - tardeba Zvlis tvinis aspiratidan damzadebuli nacxebis gamokvleviT. mll formebis dros gamoyofilia sami ZiriTadi morfologiuri forma:

• L1: patara zomis, mwiri citoplazmiT da SeumCneveli birTvebiT.• L2: ujredebi ufro didi zomis arian, vidre L1, uCveneben zomis

heterogenobas, mkafio birTvakebiT da Warbi citoplazmiT.• L3: arian didi zomis, citoplazmuri bazofiliiT, maT umetesad

aqvT citoplazmuri vakuolizacia da morfologiurad identuri arian berkitis limfomis ujredebisa.

blasturi ujredebis imunologia - mll leikemiis imunologiuri klasifikaciiT dadginda, rom limfoblastebi bevr maxasiaTeblebs iyofen normalur limfoiduri rigis ujredebTan. blasturi ujredebis imunoglobulinebis da T ujredovani receptoruli genebis gamovleniT,

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receptoruli molekulebis antigenebis eqspresia vlindeba B da T limfocitebis normaluri ganviTarebis drosac. Tumca, limfoblastebs aseve SeiZleba qondeT aberentuli genebis eqspresia damaxasiaTebeli fenotifiT, romelic maT ansxvavebs normaluri ujredebisgan.

imunologiurad mll iyofa sam ZiriTad klasad: B, pre-B da T xazovan leikemiebad.

1. B ujredovani leikemia mll-is mxolod 3%-s Seadgens da misi diagnozi damokidebulia blastur ujredebze zedapiruli imunoglobulinis gamoyofaze; limfoblastebi aseTi fenotipiT xasiaTdebian L3 morfologiiT. B-ujredovani leikemiis mesame sadiagnostiko kriteriums warmoadgens Semdegi citogenetikuri translokaciaebi: t(8;14), t(8;2)an t(2;8). B

2. pre - B ujredovani limfoiduri leikemia - bavSvTa mll-s daaxloebiT 80% moicavs limfoblastebs pre - B ujredovani fenotipiT. Ees SemTxvevebi, SesaZloa, identificirebul iqnas B ujredebis zedapiruli 2 an meti antigeniT. B xazovani leikemia antigenebis gansxvavebuli eqspresiis mixedviT ganicdis Semdgom subklasifikacias.ix qvemoT.

3. T ujredovani limfoiduri leikemia - identifikacia xdeba T ujredovan asocirebuli antigenebiT. T mll aseve ganicdis Semdgom klasifikacias adreul, Sualedur da mogvianebiT formebad.

mll-s imunologiuri daxasiaTeba, romelic mowodebulia “European group for immunological characterisation of leukaemia’s” mier ixileT Semdeg cxrilSi:

B cell lineage antigens CD19+,CD79α+ and/or CD22+pro-B-ALL no more differentiation of b cellsCommon-ALL CD10+Pra-B-ALL Cytoplasm IgM+B-ALL/B-NHL Membrane sIg+,or kappa and lambda+T cell lneage antigens CD3+,TdT+, HLA-DR andCD34-pro-T-ALL and pra T-ALL CD7+;CD2+ and/or CD5+ and/orCD8+Mild thymic T-ALL CD1a+mature T-ALL CCD3+, CD1a-,

blasturi ujredebis citogenetikuri da molekuluri diagnozi: mll-is SemTxvevaTa 90%-Si napovnia specifiuri genetikuri alteraciebi, romlebic moicavs qromosomebis raodenobriv da struqturul cvlilebebs. bavSvTa mll–is SemTxvevebis daaxloeiT naxevari moicavs Seqcevad translokaciebs. standartuli citogenetikuri analizi rutinulia kariotipis dasadgenad. magram molekuluri teqnologiebi (FISH, RT-PCR) xdeba aseve saWiro im translokaciebis identifikaciisTvis, romelTa gamoyofa ver xerxdeba rutinuli kariotipuli analiziT. aseve maTi saSualebiT SesaZloa iseTi dazianebebis aRmoCena, romlebic citogenetikurad erTnairad gamoiyureba, magram molekulurad

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gansxvavebuli arian. mkurnalobis strategiis gansazRvris dros BFM protokolis mixedviT praqtikuli mniSvneloba eniWeba BCR ABL da TEL AMl translokaciebis identifikacias.

radiologiuri kvlevebi: daavadebis gavrcelebis dadgenis mizniT ki tardeba Semdegi kvlevebi:

• lumbaluri punqcia da punqtatis morfologiuri Seswavla;

• gul-mkerdis rendgenografia pirdapir da gverdiT proeqciaSi;

• marcxena xelis rendgenografia dorsalur proeqciaSi;

• kisris, muclis Rrus ultrasonografia;

• eqokardiografia;

• eleqtrokardiografia;

• encefalografia.

• Tvalis fskeris gamokvleva;

damatebiTi kvlevebi mizanSewonilia mxolod specifiuri klinikuri niSnebis gamovlenis SemTxvevebSi.

riskis jgufebis dayofa mniSvnelovania adeqvaturi mkurnalobis gansazRvrisaTvis, recidivis ganviTarebis riskis Semcirebis mizniT. dRes msoflioSi arsebuli yvela samecniero centri da samkurnalo protokolTa avtorTa jgufebi gamoyofen sam riskis jgufs: standartuli, saSualo da maRali. BBFM swavlebis mier dadgenili riskis jgufebi ixileT samkurnalo protokolebis nawilSi.

mkurnalobis zogadi principebi: radgan leikemia sistemuri daavadebaa, misi mkurnaloba damyarebulia sistemur qimioTerapiaze. Mmll-s gansxvavebuli variantebi saWiroeben optimalur, risk faqtorebze asocirebul mkurnalobis taqtikas.

Terapiis fazebi: mll–s mkurnaloba ZiriTadad moicavs remisiis induqcias, konsolidacias, intensifikacias da dacviT Terapias. induqciis fazis daniSnulebaa remisiis (anu blastebis raodenoba Zvlis tvinSi < 5%) miRweva. Kkonsolidacia remisiis induqcias moyveba da mimarTulia eqstramedularul adgilebSi (cns, testikularebi) leikemiuri ujredebis da maTi grovebis Semdgomi Semcirebisken; intensifikacia konsolidaciis Semdgom iniSneba da mis samiznes warmoadgens darCenili rezistentuli leikemiuri ujredebi. dacviTi faza ZiriTadad moicavs oralur medikamentebs. mkurnalobis aRniSnuli protokolebis Sesaxeb informacia dawvrilebiT ixileT qvemoT.

medikamentebis kategoria: antineoplaziuri agentebi – simsivnis qimioTerapia efuZneba simsivnuri ujredebis zrdis swor gagebas da imis codnas Tu, rogor moqmedebs esa Tu is agenti maT zrdisa da gamravlebis procesze. Uujredi gayofis Semdeg gadadis zrdis fazaSi (G1 faza), rasac Semdgom moyveba DNA sinTezi (S faza), momdevno faza

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aris premitozuri faza (G2 faza), romelic mTavrdeba mitozuri ujredis gayofiT (faza M). ujredebis gayofis sixSire gansxvavebulia sxvadasxva simsivneebSi. Uufro xSirad ki simsivnuri zrda nelia normalur qsovilTan SedarebiT. aseTi gansxvaveba normalur ujredebs saSualebas aZlevs ganaxldnen ufro swrafad, vidre simsivnuri ujredebi da swored es udevs safuZvlad qimioTerapiuli reJimebis SerCevas. antineoplaziuri agentebi ujredTa reproduqciaze moqmedebs. zogierTi maTgani specifiuria ujredul ciklebze, zigierTi ara. Uujreduli apoptozi (ujredTa programuli sikvdili) aris meore potenciuri meqanizmi antineeoplasiuri agentebis. Qqimiuri preparatebis dozireba da daxasiaTeba dawvrilebiT ixileT mkurnalobis protokolSi.

mwvave limfoiduri leikemiis da misi mkurnalobis garTulebebi

mwvave lizisis sindromi, Tirkmlis ukmarisoba, sefsisi, sisxldenebi, trombozi, tifliti, neiropaTia, encefalopaTia, krunCxva, meoradi simsivneebi, zrdis hormonis deficiti.

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mwvave limfoiduri leikemiis diagnozi

inicialuri diagnozi

mwvave limfoiduri leikemiis diagnozi da biologiuri daxasiaTeba

mwvave leikemiis pirveladi diagnozi eyrdnoba periferiuli sisxlis, Zvlis tvinisa da cerebro-spinaluri siTxis citologiur kvlevebs.

Zvlis tvinis nacxebi, romelic raodenobrivad unda iyos 4 an 8, standartulad iRebeba gimzas wesiT. Mmielogramis Seswavlisas FAB klasifikaciis Tanaxmad daTvlili unda iqnas ara nakleb 500 birTviani ujredisa. citomorfologiis Semdeg tardeba standartuli citoqimiuri reaqciebi (PAS, AcP, MPO, SBB, NACE, ANAE/ANBE ± NaF). mwvave limfoiduri leikemiis diagnozi SesaZloa daisvas mxolod im SemTxvevaSi, Tu aRniSnul nacxebze aRmoCnda 25%-is toli an meti limfoblastebi. klasikuri morfologiisa da citoqimiis Semdeg saWiroa ganisazRvros mTliani kariotipis citogenetika. amis Semdeg aseve saWiroa blasturi ujredebis gamokvleva molekuluri genetikis doneze (PCR meTodiT). blasturi ujredebis biologiuri daxasiaTebis Semdgom etaps warmoadgens maTi imunofenotipireba. imunofenotipireba unda moxdes standartuli faqs-skanis meTodiT (umjobesia 4 feriani manqana). mwvave leikemiis obligatoruli diagnostikuri meTodebi aris warmodgenili Semdeg cxrilSi:

1. citomorfologia • periferiuli sisxlis saerTo analizi

• Zvlis tvinis nacxebis citomorfologia

• cerebrospinaluri siTxe: ujredebis raodenoba da citologia

• Zvlis tvinis nacxebis citoqimiuri Seswavla

2. gamdinare citometri • Zvlis tvinis da periferiuli sisxlis blastebis imunofenotipireba

3. citogenetika • blasturi ujredebis citogenetika maTSi struqturuli da raodenobrivi aberaciebis SeswavliT

4. molekuluri genetika • Zvlis tvinis da periferiul sisxlSi: PCR meTodiT mxolod SerCeviTi translokaciebis Seswavla (BCR/ABL, MLL,AF4, TEL/MLL1)

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eqtsramedularuli daavadebis diagnostikis ZiriTadi meTodebi

yvela pacienti, romelsac diagnostikis rutinuli meTodebiT daudginda mwvave leikemiis diagnozi, unda gamokvleuli iqnas Semdegi obligaturi kvlevebiT:

1. dawvrilebiTi anamnezi;2. fizikaluri gamokvleva: limfuri kvanZebis, RviZlis, elenTis da

saTesle parkebis (biWebSi) palpacia;3. lumbaluri punqcia aucileblad qimioTerapiis dawyebamde;4. gul-mkerdis rendgenografia pirdapir da gverdiT proeqciaSi;5. marcxena xelis rendgenografia dorsalur proeqciaSi;6. kisris, muclis Rrus ultrasonografia;7. eqokardiografia;8. eleqtrokardiografia;9. encefalografia da nevrologis konsultacia;10. Tvalis fskeris gamokvleva;

sxva damatebiTi kvlevebi mizanSewonilia mxolod spefifiuri situaciebis SemTxvevaSi da is unda gadawydes protokolis adgilobrivi da centralur koordinatorebTan diskusiis Semdeg.

centraluri nervuli sistemis diagnozi da centraluri nervuli sistemis leikemiis definiciebi

rogorc aRvniSneT, lumbaluri punqcia aucilebeli nawilia mwvave leikemiis inicialuri diagnostikuri meTodebis da is yovelTvis unda Catardes qimioTerapiis dawyebamde. lumbaluri punqcia yovelTvis saWiroa centraluri nervuli sistemis inicialuri statusis Sesaswavlad. imavdroulad, intralumbalurad keTdeba metotreqsati (MTX). miRebuli siTxe gamoikvleva, rogorc citologiurad, aseve bioqimiuri maCveneblebis mixedviT. ujredebis raodenobrivi maCveneblebis garda cerebrospinaluri siTxisgan unda damzaddes sul mcire 1 nacxi, romelic Semdgom gamoikvleva morfologiurad. cerebrospinalur siTxeSi ujredebis raodenobis morfologiis da pacientis klinikuri da radiologiuri monacemebis safuZvelze miRebulia centraluri nervuli sistemis inicialuri dazianebis Semdegi definiciebi:

1. centraluri nervuli sistemis uaryofiTi statusi:

• pacients ar aReniSneba centraluri nervuli sistemis klinikuri gamovlinebis arc erTi niSani;

• cerebrospinaluri siTxe aris blastebisagan Tavisufali;

• Tvalis fskeris gamokvlevisas ar aReniSneba paTologiuri cvlilebebi.

2. centraluri nervuli sistemis pozitiuri statusi:

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• cerebrospinalur siTxeSi ujredebis raodenoba metia 5 /l –ze;

• pacients aReniSneba centraluri nervuli sistemis dazianebis klinikuri niSnebi (Tavis nervebis parezi) im SemTxvevaSic ki, rodesac cerebrospinaluri siTxe aris blastebisagan Tavisufali da ar vlindeba radiologiuri cvlilebebi Tavis tvinis kompiuteruli tomografiis an magnitur-rezonansuli kvlevebiT (Ingram LC et al. 1991, Smith M et al. 1996);

• pacients aReniSneba masis efeqti Tavis tvinSi an meningialur garsebSi kompiuteruli tomografiis an magnitur-rezonansuli kvlevebiT;

• paTologiuri cvlilebebi retinaze im SemTxvevaSic ki, rodesac cerebrospinaluri siTxe Tavisufalia blastebisagan da ar gvaqvs masis efeqti kompiuteruli tomografiis an magnitur-rezonansuli kvlevebiT (Smith M et al. 1996).

SeniSvna: amrigad, centraluri nervuli statusis Seswavlis rutinuli meTodebi aris cerebrospinaluri siTxis citomorfologiuri kvleva da Tvalis fskeris Seswavla. sxva yvela danarCeni kvlevebi pacients utardeba mxolod im SemTxvevaSi, rodesac eWvi aris mas efeqtze da igi wydeba protokolis koordinatorTan SeTanxmebiT.

ConCxis statusis Sesaswavli diagnostikuri meTodebi

ConCxis statusis Sesaswavli diagnostikuri meTodebi tardeba mxolod im SemTxvevaSi, rodesac pacients aqvs aRniSnuli sistemis dazianebis klinikuri gamovlinebebi – saxsrebisa da Zvlebis tkivili, moZraobis SezRudva an Zvlebis spontanuri motexiloba diagnozis dasmis momentSi. kvlevebi moicavs gul-mkerdis, xerxemlis rendgenografias 2 proeqciaSi. ConCxis Seswavla ar gansazRvravs mkurnalobis Semdgom taqtikas da igi saWiroa mkurnalobaze pasuxis dinamikaSi Sesaswavlad.

saTesle parkebis statusis Seswavla (biWebSi)

saTesle parkebis statusis Seswavla (biWebSi) keTdeba mxolod im SemTxvevaSi, rodesac pacients aReniSneba saTesle parkebis mktkivneuloba da SeSupeba. rutinuli kvleva aris orive saTesle parkis sonografiuli gamokvleva. inicialuri biofsia rutinulad ar gamoiyeneba, magram im SemTxvevaSi, Tu pacients darCa saTesle parkebis mktkivneuloba da SeSupeba qimioTerapiis remisiis induqciis kursis Semdegac, misi riskis jgufSi Semdgomi stratifikaciis mizniT saWiroa Catardes biofsia Semdgomi citologiuri kvleviT.

hemostazis inicialuri diagnostika

hemostazis inicialuri diagnostika utardebaT mxolod im pacientebs, romlebsac memkvidreobaSi aReniSnebaT Tandayololi hemokuagulopaTiebi an pacientebs, romelTac diagnozisas aReniSnebaT mZime hemoragiuli sindromi. kvleva moicavs srul koagulogramas.

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am TavSi mocemuli diagnostikuri kvlevebi unda Catardes pacientis klinikaSi moTavsebisTanave da ar unda gagrZeldes 48 saaTze met xans.

ALL IC-BFM 2002 mkurnalobis sqema

Sesavali

ALL IC-BFM 2002 samkurnalo protokili eyrdnoba germanuli hematologiuri mimdinareobis 25 wlian sarwmuno statistikur monacemebze dafuZnebul gamocdilebas da misi ZiriTadi mizania, erTis mxriv, gazardos gadarCenis sixSire, xolo, meores mxriv, Seamciros qimioTerapiis toqsiuroba riskis jgufebis zusti stratifikaciis xarjze.

aRniSnuli samkurnalo protokoli ukve bolo aTwleulis ganmavlobaSi gascda germaniis sazRvrebs da masSi monawileobas iRebs evropis mravali qveyana da Sesabamisad marTvis komiteti dakompleqtebulia sx/sx qveynebis warmomadgenlobiT: J.Stary, L .Castilio, M. Schrape, G.Masera, H. Riehm.

ALL IC –BFM 2002 mudmivad ganaxlebadi swavlebaa, masSi monawile qveynebi yovelwliurad ikribebian samuSao viTarebaSi (I - BFM meeting), sadac ganixileba yvela arsebuli problema da mecnieruli siaxle. unda aRiniSnos, rom saqarTvelo bolo ori welia am SexvedrebSi damswris statusis monawileobs, xolo momavali wlidan igegmeba Cveni am did ojaxSi oficialurad gaerTianeba.

yvela qveynis adgilobrivi statistikuri monacemebi sabolood muSavdeba BFM swavlebis samecniero centris mier da 5 wliani analizis Semdeg adgili aqvs protokolSi mniSvnelovani cvlilebebis danergvas. axali samkurnalo protokolis saxelwodeba formdeba mimdinare wlis numeraciiT da xdeba praqtikuli samkurnalo saxelmZRvanelo momdevno 5 wlis ganmavlobaSi.

ALL IC –BFM 2002 oficialurad damTavrdeba 2007 wlis bolos, ris Semdegac gaixsneba axali protokoli.

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protokolis moTxovnebi

1. Pprotokoli oficialurad unda iqnes miRebuli da damtkicebuli qveynis janmrTelobis dacvis organoebis mier, rogorc leikemiis mkurnalobis saxelmwifo standarti.

2. Pprotokolis ganmxorcielebel samedicino dawesebulebas unda gaaCndes:

• BFM tipis Terapiis adeqvaturi gamocdileba:

• Tanmxlebi TerapiisaTvis saWiro infrastruqtura da gamocdileba;

• protokoliT dadgenili yvela diagnostikuri meTodebis Semswavleli aRWurviloba da Sesabamisi samedicino personali;

3. aRniSnuli protokolis mixedviT mkurnaloba utardebaT mxolod im pacientebs, romelTa asaki moicavs 0-dan 18 wlis CaTvliT.

4. Yyvela pacients mkurnaloba utardeba protokoliT dadgenili standartebis farglebSi da individualuri Terapiis SerCeva da gamoyeneba miuRebelia.

5. yvela pacienti pirveli 24 – 74 saaTis ganmavlobaSi registrirdeba, rogorc nacionalur registraciis centrSi, aseve protokolis mmarTvel saerTaSoriso saTavo ofisSi.

6. yvela pacienti da mSobeli informirebuli unda iyos aRniSnuli protokolis ZiriTad mimarTulebaze, naTlad unda iqnas axsnili mkurnalobis intensifikaciis mizezebi ara B uWredovani leikemiebis SemTxvevaSi, mkurnalobis efeqturobis garda mTlianad unda gaecnos mosalodnel adreul Tu Soreul garTulebebebs. aRniSnuli informacia unda gaformdes oficialuri dokumentaciis saxiT.

7. Pprotokolis ganmxorciebeli samedicino dawesebuleba valdebulia uzrunvelyos pacienta anonimuroba pacientTa globalur populaciaSi mimarTebiT.

8. protokols unda yavdes nacionaluri koordinatori, romelsac aqvs adeqvaturi ganaTleba, gamocdileba da pasuxismgebloba, gadawyvitos lokaluri problemuri sakiTxebi pacientis marTvis nebismier etapze saerTaSoriso samecniero IC-BFM centrTan diskusiis da SeTanxmebis safuZvelze.

9. protokolis aRmnusxveli samedicino dokumentacia “istoria” unda iyos srulyofili da unda Sedgebodes Semdegi nawilebisgan:

- pacientis sapasporto monacemebi (gvari, saxeli, dabadebis TariRi, misamarTi)

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- sruli diagnozebi, rogorc mimdinare, aseve ukve arsebuli maTi dasmis zusti TariRebiT (Tanmimdevrobis dacviT). yoveli momdevno diagnozi pacientis aRricxvidan moxsnamde dinamikaSi emateba amave furcels. yoveli Ddiagnozis Semdeg emateba mkurnalobis dasaxeleba da misi Catarebis zusti vadebi (dRe, Tve, weli)

- daavadebis samkurnalo protokolis dizainis da Terapiuli gegmis aslebi, romlebic ivseba konkretuli pacientisTvis. nimuSebi ix. qvemoT. - paTologiuri nawili – citologiuri, histologiuri, genetikuri da imunologiuri kvlevebis daskvnis originalebi, Semsruleblis xelmoweriT.

- klinikuri laboratoriuli kvlevebis nawili.

- daniSnulebis furclis nawili yoveldRiuria, moicavs mxolod Tanmxleb Terapias, pacientis sasicocxlo funqciebis maCveneblebs, wonas, diurezs, defekacias, Rebinebis Sesaxeb informacias da misi meore gverdi eTmoba eqimis yoveldRiur mokle Canawerebs arsebuli problemebis CamonaTvaliT. - sxvadasxva specialistis mier Catarebuli konsultaciebis an manipulaciebis dokumentacia.

- radiologiuri kvlevebis daskvnis originalebi.

- eqimis werilebi: eqimis werilebi msgavsia etapuri epikrizebis da srulad unda asaxavdes informacias daavadebis yvela etapze diagnozis dasmidan da pacientis aRricxvidan moxsnamde:

- diagnozis dasmisas eqimi valdebulia aRweros yvela standatulad damtkicebuli diagnostikuri meTodi da maTi Sedegebis safuZvelze mecnierulad daasabuTos diagnozis siswore.

- mkurnalobis periodSi eqimi wers epikrizebs TiToeuli qimioTerapiuli kursis damTavrebis an, ukidures SemTxvevaSi, misi Sewyvetis dros. aRniSnul werilSi eqimi zustad aRwers mkurnalobis Sedegebs (pasuxs qimioTerapiaze protokoliTve damtkicebuli TariRebiT), garTulebebs, aseve mecnierulad asabuTebs raime tipis cvlilebebs mkurnalobis dros, Tuki mas adgili hqonda da saxavs mkurnalobis Semdgom etaps TariRis miTiTebiT.

- mkurnalobis dasrulebisas iwereba sruli epikrizi. eqimis yvela werili unda iyos dabeWdili saxiT da mas eqimTan erTad xels unda awerdes ganyofilebis xelmZRvaneli da protokolis koordinatori.

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- pacientis an misi MmSobelTan gaformebuli dokumentaciis nawili – Tanxmobis werili, werili Terapiis Sewyvetis Sesaxeb Tu am ukanasknels eqna adgili.

mkurnalobis dizaini

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risk-jgufebis definicia

standartuli riskis jgufi (SR)

- periferiul sisxlSi me-8 dRes blastebis raodenoba < 1000 - /µL.- asaki > 1 welze – < 6 welze- leikocitebis inicialuri raodenoba < 20 000/µL- M1 an M2 Zvlis tvini me-15 dReze- M1 Zvlis tvini 33-e dReze

standartuli riskis jgufis pacienti unda akmayofilebdes srulad yvela zemoCamoTvlil kriteriums.

saSualo riskis jgufi (IR)

1. - periferiul sisxlSi me-8 dRes blastebis raodenoba naklebia 1000 - /µL- asaki < 1 welze an > 6 welze an leikocitebis inicialuri

raodenobs > 20 000/µL- M1 an M2 Zvlis tvini me-15 dReze- M1 Zvlis tvini 33-e dReze

2. – standartuli riskis kriteriumebi magram M3 Zvlis tvini me-15 dRezeda M1 Zvlis tvini 33-e dReze

maRali riskis jgufi (HR)

1. saSualo riskis jgufi da M3 Zvlis tvini me-15 dReze (ara standartuli riski da M3 Zvlis tvini me-15 dReze!)

2. periferiul sisxlSi me-8 dReze blastebis raodenoba > 1000/µL-ze3. M2 an M3 Zvlis tvini 33-e dReze4. translokaciebi t(9;22) [BCR/ABL] an t(4;11) [MLL/AF4]

maRali riskis jgufis pacienti unda akmayofilebdes sul mcire 1 zemoT mocemul kriteriums.

riskis jgufebis definicia asakis inicialuri leikocitebis raodenobis me-8 dReze prednizolonze pasuxis me-15 da 33-e dRis Zvlis tvinSi blastebis raodenobis mixedviT ixileT Semdeg sqemaSi:

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mkurnalobis klasificacia riskis jgufebis dinamikaSi gadanawilebiT

diagnozime-8 dRe

dRe 15

dRe 33

riskis jgufi

jgufebis % 33% 48% 19%recidivebis % 14% 38% 48%5 wliani gadarCena 90.6% 80.9% 47.0%

SeniSvna: M1 - blasturi ujredebi Zvlis tvinSi < 5%M2 - blasturi ujredebi Zvlis tvinSi > 5 - < 25M2 - blasturi ujredebi Zvlis tvinSi > 25

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asaki 1-5; da lieikocitebi 20,000; da blastebi Mme-8 dReze < 1,000

asaki <1-5 an > 6 an lieikocitebi 20,000 an blastebi Mme-8 dReze < 1,000

t (9;22), t(4;11) an blastebi Mme-8 dReze >1,000

M1/M2 M3 M1/M2 M3 M1/M2/ M3

M1 M2 /M3 M1 M2/M3 M1/M2/M3

SR IR HR

Terapiuli strategia riskis jgufebis mixedviT

standartuli riskis pacientebi pre-B ujredovani mwvave limfoiduri leikemiiT remisiis induqciaSi Rebuloben mxolod 2 dozas daunorubicinisa (Protocol 1'), radgan rogorc statistikurma monacemebma aCvena, aseTi reduqcia usafrTxoa da aranairad ar zrdis recidivis sixSires. yvela sxva pacienti, standartuli riskis ara pre-B ujredovani, saSualo riskis da maRali riskis jgufis remisiis induqciaSi miiRebs daunorubicinis 4 dozas (Protocol 1).

induqciis damTavrebidan 2 kviris Semdeg yvela pacientTan iwyeba konsolidaciis faza, romelic efuZneba leikemiis imunologiur tips. T ujredovani pacientebi, sul erTia, romel jgufs ganekiTvnebian isini, standartuls Tu saSualos, unda miiRon protokoli M (MTX 5g/m2/24sT-Si x 4), radgan am populaciaSi Catarebuli farmakodinamiurma da klinikurma statistikam aCvena, rom MTX–is efeqturoba T ujredovani leikemiebis SemTxvevaSi pirdapir proporciulia MTX–is maRal dozasTan (Barredo JC et al. 1994, Belkov VM et al. 1999, Reiter A et al. 1994, Rots MG et al. 1999, Synold TW et al. 1994). maSin, roca standartuli da saSualo riskis pre-B ujredovani leikemiis mqone pacientebi miiReben protokoli mM (saSualo dozis MTX 2g/m2 /24sT-Si x 4).

konsolidaciidan 2 kviris Semdeg yvela pacienti nebismieri riskis jgufidan miiRebs intensifikaciuri Terapiis 2 randomizirebul mxars. standartuli riskis (SR) pacientebi, romlebic miekuTvnebian randomizirebuli mkurnalobis pirvel mxars, miiReben protokol II-s, xolo pacientebi, romlebic miekuTvnebian randomizirebuli mkurnalobis meore mxars, miiReben protokoli III-s x 2 maT Soris 10-Tviani oraluri merkaptopurinisa da MTX-is dacviTi TerapiiT. saSualo riskis pacientebi (IR), romlebis ganekuTvnebian randomizirebuli mkurnalobis pirvel mxars, aseve miiReben protokol II-s x 1 maSin, rodesac pacientebi, romlebic miekuTvnebian randomizirebuli mkurnalobis meore mxars, miiReben protokoli III-s x 3 Semdgomi 4-kviriani oraluri merkaptopurinisa da MTX-is dacviT Terapias protokolebs Soris. sabolood intensiuri Terapiiis damTavrebidan 2 kviris Semdeg yvela pacienti, biWebis CaTliT, miiRebs dacviT Terapias 6 merkaptopuriniTa da MTX-iT 24 Tvis ganmavlobaSi.

pacientebi, romlebic miiReben protokol mM-s kompensatorulad, dacviT Terapiaze miiReben 4 intratekalur MTX-s standartuli da saSualo riskis pirvel mxrebSi da 2 intratekalur MTX-s saSualo riskis meore mxarSi. ra Tqma unda, is ar iqneba saWiro im pacientebisaTvis, romlebic ganekuTvnebian saSualo riskis meore mxars, radgan isini Rebuloben adeqvatur centraluri nervuli sistemis profilaqtikas x 3 protokoli III-is dros. aseve damatebiT punqcias ar saWiroeben T ujredovani

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leikemiis mqone pacientebi, rameTu konsolidaciis dros maRali dozis MTX-s Rebuloben. samagierod, es pacientebi qimioTerapiis damTavrebis Semdeg gadian profilaqtikur Tavis tvinis dasxivebas. pre-B ujredovani leikemiis mqone pacientebi profilaqtikur Tavis dasxivebas ar Rebuloben. gamonakliss warmoadgens mxolod centraluri nervuli sistemis inicialuri dazianebis mqone pacientebi, romelTa asaki >1 welze da isini Rebuloben Tavis tvinis Terapiul dasxivebas.

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protokoli I’ – I

protokoli I' standartuli riskis pre-B ujredovani pacientebisaTvis

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protokoli I standartuli riskis T, saSualo da maRali riskis mqone pacientebisaTvis

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protokoli I da protokoli I’ aRwera

pirveli faza

PRED (prednizoloni): 60 mg/m2/dReSi peroralurad an intravenurad 3 miRebaze.

dRe 1 – 7: daiwye kalkulirebuli dozis 25 % da nel-nela gazarde misi doza. sruli doza pacientma unda miiRos me-4 dRes. im SemTxevvaSi, rodesac pacients aReniSneba inicialuri leikocitebis maRali ricxvi an mniSvnelovani organomegalia, mosalodnelia simsivnis mwvave lizisis sindromis ganviTareba. aRniSnuli sindromis profilaqtikuri da samkurnalo RonisZiebebi ixileT programis protokolebis nawilSi.

dRe 8 - 28: PRED 60 mg/m2/dReSi oralurad gayofili 3 dozaze, radgan prednizolonuri Terapiis dros maRalia wylulovani daavadebis ganviTarebis riski. profilaqtikurad miRebulia H2 blokatoris miReba.

dRe 29: iwyeba PRED dozis kleba, romelic grZeldeba 9 dRis ganmavlobaSi yovel me-3 dRes sawyisi dozis ganaxevrebiT.

VCR (vinkristini): 1,5 mg/ m2/dReSi intravenurad (maqsimaluri doza 2 mg) 8, 15, 22, 29 dRes. saSualo simZimiT gamoxatuli VCR-Tan asocirebuli neiropaTia ar aris mizezi medikamentis Secvlisa an amoRebisa remisiis induqciis fazidan. im SemTxvevaSi, Tu gamoixata mZime neiropaTia, SemTxveva ganxiluli unda iyos protokolis nacionalur koordinatorTan.

VCR iSviaTad xdeba mizezi antidiurezuli hormonis sekreciis Seusabamobis sindromisa (SIADH sindromi), romelsac Tan axlavs neirotoqsiurobis klinikuri niSnebi da safiqrebelia, rom igi gamowveulia VCR-is toqsiuri zemoqmedebiT hipoTalamusis supra optikur birTvebze.

DNR (daunorubicini): 30 mg/m2/dReSi intravenurad 1 saaTis ganmavlobaSi.

• x 2 me- 8 da me-15 dRes protokol I'-Si• x 4 me- 8, 15, 22 da 29-e dReebze protokol I-Si

eqokardiografia iTvleba standartul kvlevad aRniSnuli preparatebis kardiotoqsiurobis Sesamowmeblad da im SemTxvevaSi, rodesac Semoklebis fraqcia (SF) < 30% an gamoxatulia gulis dazianebis klinikuri niSnebi, DNR-is Secvla

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an reducireba ganxilul unda iqnas protokolis nacionalur koordinatorTan.

ASP E.col L-asparaginase: 5 000 U/m2/dReSi intravenurad 1 saaTis ganmavlobaSi me-12, 15, 18, 21, 24, 27, 30, 33 dReebze. im SemTxvevaSi, Tu pacients gamoexata hipersensitiuri reaqcia aRniSnul preparatze, rekomendirebulia misi Secvla EG-ASP 1.000U/m2/dReSi. ASP-s infuziis win yovelTvis keTdeba testi 10-50 erTeuli an 0,2 erTeuli kilogramze intravenurad 15 wuTis ganmavlobaSi. testis Semdeg velodebiT 30 wuTis ganmavlobaSi. Tu testi dadebiTia ASP unda gadaisxas antihistaminuri da steroiduli preparatebis qolgiT.

SeniSvna: testis uaryofiToba 100 %-iT ar gamoricxavs mosalodnel alergiul reaqcias. amitom, pacienti saWiroebs meTvalyureobas uSualod gadasxmis dros da misi damTavrebidan aranakleb 6 saaTisa.

ASP-m erTdroulad SeiZleba gamoiwvios Trombozebis ganviTareba da sisxldenebi. Tu pacients ASP-s infuziebis mimdinareobisas aReniSna koagulopaTiisaTvis saxasiaTo klinikuri niSnebi, saWiroa gakeTdes sruli koagulograma da saWiroebis SemTxvevaSi moxdes plazmuri faqtorebis Sevseba. ASP-s erT-erT garTulebas warmoadgens hiperglikemia. amitom, ASP-iT mkurnalobis periodSi saWiroa sisxlsa da SardSi Saqris kontroli. aRniSnuli garTuleba imarTeba insuliniT. im SemTxvevaSi, Tu gamoixata klinikurad – Rebineba, gulisreva, Zlieri sartyliseburi tkivili welis midamoSi, laboratoriulad – lipazasa da aminazas maRali done da radiologiurad – pankreasis struqturis Secvla dadasturebuli pankreatiti ASP unda amoRebuli iqnas mkurnalobidan.

MTX (IT) intra-tekaluri keTdeba 1, 12, 33, 45 da 59 dReebze. metotreqsatis dozebi asakobrivia da mocemulia Semdeg cxrilSi:

asaki <1 1<2 2<3 >3dozireba (mg) 6 8 10 12

SeniSvna: mkurnalobis pirveli faza maqsimalurad unda iqnas daculi, rogorc medikamentebis dozirebiT, aseve maTi Seyvanis vadebiT. gamonakliss warmoadgens mxolod sicocxlisaTvis SeuTavsebeli garTuleba.

meore faza

meore fazis dawyebis kriteriumebi:

• damakmayofilebeli zogadi mdgomareoba;

• pacients ar aqvs mZime infeqciebi;

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• kreatininis done unda Seesabamebodes asakobriv normas;

• hematologiuri maCveneblebi:- leikocitebis raodenoba =2,000/ì L- granulocitebi =500/ì L- Trombocitebi =50,000/ì L

citozaris blokis dawyebis kriteriumebi:

• leikocitebi =500/ì L• Trombocitebi =30,000/ì L

citozaris blokis gawyveta ar SeiZleba. citozaris bloks Tan unda axldes merkaptopurinis miReba. am ukanasknelis gamotoveba SesaZlebelia blokebs Soris SualedSi ise, rom kumulaciuri doza unda iyos 1.680 mg/m2.

meore ciklofosfamidis (CPM) dawyebis kriteriumebia:

• leikocitebi =1,000/ì L• granulocitebi =300/ì L• Trombocitebi =50,000/ì L• kreatininis done unda Seesabamebodes asakobriv normas

CPM: 1000 mg/m2/dReSi intravenurad 1 saaTis ganmavlobaSi 36-e da 64-e dReze. CPM-is gadasxmis dros unda gatardes Semdegi RonisZiebebi:

• diurezisa da cistitis profilaqtikisTvis intravenurad hidracia 3,000 ml/m2/24sT_Si (glukoza 5%, fiziologiuri xsnari 0,9%, kaliumis qloridi 4% 30 ml)

• gansazRvre diurezis saaTobrivi da sadReRamiso raodenoba da Seadare miRebuli da gadasxmuli siTxeebis raodenobas. Tu gamoyofili siTxis raodenoba miRebuli siTxis raodenobaze metia 400 ml/m2/12 saaTSi, daiwye furosemidis ineqciebi sawyisi doziT 0,5mg/kg (maqsimaluri 20 mg) diurezis aRdgenamde.

• uromiteqsani 400 mg/m2 intravenurad 0, 4 da 8 saaTze ciklofosfamis dawyebidan.

• Tu pacients gamoexata hematuria an mtkivneuli Sardva, saWiroa hidraciis gazrda 4,500-dan 5,000ml/m2/24 saaTSi, furosemidi 0,5 – 1 mg/kg intravenurad yovel 6 saaTSi erTxel. tkivilis SemTxvevaSi gamoiyeneT analgeziuri saSualeba, aseve SegiZliaT gamoiyenoT uromikeqsanis damatebiTi infuzia.

ciklofosfamidma iSviaTad SeiZleba gamoiwvios SIADH sindromi. aRniSnuli sindromis marTvis gaidlaini ixileT programis protokolebis nawilSi.

MP: 6 – merkaptopurini 60mg/m2/dReSi oralurad 36 – 63 dReebi. merkaptopurini unda miiRos saRamos rZis gareSe.

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ARA – C: citozari 75mg/m2/dReSi intravenurad 4 dRis ganmavlobaSi 4 blokis saxiT. dReebi 38 – 41; 45 - 48; 52 - 55 da 59 - 62

MTX IT: intratekaluri metotreqsati imave dRes, roca iwyeba citozaris meore bloki (dRe 45-e) da citozaris meoTxe bloki (dRe 59-e). metotreqsatis dozebi asakobrivia da mocemulia Semdeg cxrilSi:


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konsolidaciuri Terapia standartuli da saSualo riskis mwvave limfoiduri leikemiebisTvis

protokoli mM

dizaini

24

ALL-BFM-95-Tan SedarebiT aRniSnul protokolSi adgili aqvs garkveul siaxles. gansxvaveba exeba metotreqsatis dozas. kerZod, pre-B ujredovani limfoiduri leikemiis standartuli da saSualo riskis pacientebs igi eZlevaT doziT 2g/m2/24sT-Si x4. meores mxriv, centraluri nervuli sisitemis recidivis riskis Sesamcireblad aseT pacientebs reinduqciis an dacviT Terapiaze utardebaT kompensatoruli intra-tekaluri metotreqsati. orive SemTxvevaSi es iqneba 5g/m2 Tu 2g/m2

leikovoriniT dacviTi RonisZiebebi erTnairia. protokoli mM iwyeba protokoli I da protokoli I’ damTavrebidan 2 kviris Semdeg. qimioTerapiis doza axlidan gadaangariSdeba arsebuli simaRlisa da wonis mixedviT dadgenili zedapiris farTze iseve, rogorc TiToeuli metotreqsatis gadasxmis win. ix. protokolis dizaini:

protokoli mM dawyebis kriteriumebi:

• sruli citomorfologiuri remisia (Zvlis tvinis punqcia aucilebelia)

• kargi zogadi mdgomareoba

• pacients ar aReniSneba mZime infeqcia

• kreatinini da kreatininis klirensi asakobrivi normis farglebSi

• pacients ar aReniSneba saSarde gzebis obstruqcia

• RviZlis funqciebi: ALT/AST 5 x asakobrivi norma bilirubini 3 x asakobrivi norma

• sisxlis ujredebis maCveneblebi:leikocitebi =1,500/ì Lgranulocitebi =500/ì LTrombocitebi =50,000/ì L

MP (merkaptopurini) 25mg/m2/dReSi oralurad 1 - 56 dRe saRamos Wamidan 2 saaTis Semdeg.

MD MTX (saSualo dozis metotreqsati): 2,000mg/m2/24sT-Si x 4 yovel me-14 dRes, anu me-8, 22-e 36-e da 50-e dReebze.

HD MTX (maRali dozis metotreqsati): 5,000mg/m2/24sT-Si x 4 yovel me-14 dRes, anu me-8, 22-e 36-e da 50-e dReebze.

TiToeuli metotreqsatis gadasxmis Terapiuli gegma Semdegia:

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maRaldozirebuli metotreqsatis infuziisTerapiuli gegma

E H

dRe 0 ....../...... sruli bioqimiuri analizi (kreatininis klirensiT da Sedardes asakobriv normas).

daigegmos MTX koncentraciis plazmaSi gansazRvra!

infuzia : ........ ml/24 sT. (3000ml /m2) - Gluc. 2,5%/NaCl 0,45% 500 + KCl 4% 30/500ml) +NaHCO 5% 70 /500ml

dRe 1 ..../.... 12.00 ganisazRvros Sardis pH da Tu < 7,0:

NaCHO3 5% 60 ml/m2) i.v. ½ sT-is ganmavlobaSi, ZiriTadi infuziis paralelurad

14.00 Methotrexat (Methotrexat ® ) ........mg (5000mg/m2) 24 sT-Si i.v. 13.30 sT : MTX(10%) .......mg (.......ml) 30 xT -Si. i.v. 14.00 sT : MTX(90%) ....... mg 24 saaTSi . p.i.:

sadReRamiso metotreqsati nawildeba sadReRamiso sainfuzio flakonebSi:24 saaTSi sumaruli siTxis raodenoba (3000ml/m2) ...................... mlTiToeul 500 (NaCl 0,45% + Clucosae 2,5%) + NaCHO 5% 50 +KCl 4% 30 + MTX ( mg) MTX - is dasaSvebi koncentraciiT : 25 mg/ml

xsnarebi mzaddeba erTdroulad, ewereba pacientis gvari, damzadebis TariRi. pirveli idgmeba gadasaxmelad, xolo danarCenebi (N =) inaxeba macivarSi.

infuzomatze mieTiTos ml/sT –Si 15.00 : LP ..... mg MTX i. th. (1 saaTis Semdeg I/V Mmetotreqsatis

dawyebidan)

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saxeli asaki

L = ........... cm

KG = ............ kg

S = ............ m2

metotreqsatisDdawyebis hematologiurikriteriumebi: Leu≥ 1500 /µl; Gran ≥ 500 /µl; Thro ≥ 50 000/µl,

dRe 2 ..../....

14.00 : isazRvreba MTX 24 (yovelTvis!) da keTdeba pataraBbioqimia

Tu MTX 24 = N, iwyeba infuzia Semdgomi 48 saaTis ganmavlobSi

........ ml/24 sT (3000ml/m2) (Gluc2,5%/NaCl 0,45% + KCl 4% 30) + NaCHO3 5% 50 ml pro 500 ml

- Tu MTX 24 maRalia, daiwye saswrafo RonisZiebebi!!! (ix. saswrafo RonisZiebebi 24sT)

02.00: Tu MTX 24 =N , MTX 36 aiReT, SeinaxeT da gansazRvreT diliT 08.00

dRe 3 ..../....

08.00: isazRvreba MTX 42 (yovelTvis) da keTdeba: Leucovorin (42saaTiani) ..... mg i.v. (15 mg/m2) - Tu MTX42 =N, grZeldeba infuzia (3000ml/m2)

- Tu MTX42 done maRalia, iwyeba saswrafo RonisZiebebi (ix. saswrafo RonisZiebebi 36, 42, 48sT)

14.00: isazRvreba MTX 48 (yovelTvis) da keTdeba: Leucovorin (48 saaTiani)....... mg i.v. (15 mg/m2)

- Tu MTX48 = N, grZeldeba infuzia (3000ml/m2)

- Tu MTX48 maRalia, iwyeba saswrafo RonisZiebebi (ix. saswrafo RonisZiebebi 36, 42, 48sT)

20.00: Leucovorin (54 saaTiani) .......mg i.v. (15 mg/m2) MTX 54 isazRvreba mxolod im SemTxvevaSi, Tu pacientma aCvena winamorbedi maRali done da Sesabamisad grZeldeba saswrafo RonisZiebebi 36, 42, 48sT

dRe 4 ..../....

08.00 : bioqimia srulitoqsiurobis SemTxvevaSi isazRvreba MTX 66 da 72 (ix. MTX 54-is maRali done)

27

MTX is normebi : MTX24 < 150 ; MTX36 < 3; MTX42 ≤ 1; MTX48 ≤ 0,4 ; MTX 54 ≤ 0,4 µmol/l

saswrafo RonisZiebebi 24sT

MTX 24 maRali done an mosalodnelia cudi eliminacia arsebuli klinikuri monacemebis (kreatinis mniSvnelovani mateba, diurezis Semcireba, SeSupeba, hipertenzia, saswrafod unda daiwyos Semdegi Ronisziebebi!!!!!siTxis raodenoba gaizardos 45,000 ml/m²/24 saaTSiforsirebuli diurezi 1 – 10 mg/kg Sardis alkalizacia - NaHCO3-40-80 mmol/l (100-200mmol/m²)siTxis balansis kontroli sxeulis masis da gamoyofili SardiT. am SemTxvevaSi unda ganisazRvros MTX 36.

saswrafo RonisZiebebi 36, 42, 48

- izrdeba infuzia 4500 ml 24 saaTSi kargi diurezis SenarCunebiT- leikovoriniT damatebiTi dacva yovel 6 saaTSi erTxel Semdegi sqemiT:

MTX µmol/L LCV mg/m²

4 – 5 75mg/m²

3 - 4 60mg/m²

2 - 3 45mg/m²

1 - 2 30mg/m²

0.25 - 1 15mg/m²

leikovoriniT dacva grZeldeba yovel 6 saaTSi erTxel, sanam metotreqsatis done ar miaRwevs 0.25µmol/L.

Tu Sesayvani leikovorinis doza metia, 20 mg/kg gadaasxi 1 saaTis ganmavlobaSi Ca-iT gamowveuli bradikardiis Tavidan acilebis mizniT.

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karboqsipeptidazes daniSvna xdeba im SemTxvevaSi, Tu:

1 36h-MTX > 10µmol/L2 42h-MTX > 5µmol/L3 48h-MTX > 3µmol/L4 kearatininis done > 1,5 normasTan SedarebiT da gvakvs oliguria

Ddoza: Carboxypeptidase: 50U/kg neli nakadiT (15wT)

MTX IT (intra-tekaluri metotreqsati): x4 yoveli metotreqsatis infuziisas. metotreqsatis dozebi asakobrivia da mocemulia Semdeg cxrilSi:

asaki <1 1<2 2<3 >3dozireba (mg) 6 8 10 12 LCV (leikovorini): 15mg/m2 intra-venurad samjer 42, 48, 54 sT-ze

metotreqsatis infuziis dawyebidan.

29

reinduqciuri Terapiis mxari Istandartuli da saSualo riskis pacientebisaTvis

protokoli II SR-1 / IR-2 / HR-2B

dozebisa da dizainis mixedviT aRniSnuli Terapiuli elementi ALL BFM 95-is Sesabamisi protokolis identuria da Sedgeba 2 fazisgan. is gamoiyeneba standartuli da saSualo riskis mqone pacientebSi erTxel mogvianebiTi reinduqciuri Terapiis saxiT da iwyeba mMMprotokolis damTavrebidan 2 kviris Semdeg. aseve es protokoli gamoiyeneba reinduqciur TerapiaSi maRali riskis mqone pacientebSi meore mxarSi x2 HR 3 blokis damTavrebis Semdeg.

protokoli II dizaini:

30

protokolis dawyebis kriteriumebi:

• sruli remiisiis gagrZeleba (Zvlis tvinis punqcia aucilebelia)

• kargi zogadi mdgomareoba


• sisxlis ujredebis maCveneblebi:leikocitebi =2,500/ì Lgranulocitebi =1,000/ì LTrombocitebi =100,000/ì L

protokoli II faza I:

aRniSnuli fazis regulaciis kriteriumebi:

• mZime neiropaTiis SemTxvevaSi VCR (vinkristini) SeiZleba amoRebul iqnas;

• granulopoeezis ukmarisobis SemTxvevaSi (leikocitebi < 500/ì L an granulocitebi < 200/ì L) doqsorubicinisa da vinkristinis doza SeiZleba iqnas gadatanili.

DEXA (deqsametazoni): 10mg/m2/dReSi oralurad an intra-venurad gayofili 3 dozaze, 1-21 dRe. 22-e dRidan iwyeba misi safexureobrivi Semcireba, yovel mesame dRes dozis naxevriT da grZeldeba 9 dRis ganmavlobaSi.

radgan deqsametazoni aris wylulovani daavadebis ganviTarebis riski, saWiroa H2 lokatoris gamoyeneba. Zlierad gamoxatuli gastritis SemTxvevaSi saWiroa Catardes Sesabamisi RonisZiebebi, romlis marTvis gaidlaini SegiZliaT ixiloT garTulebebis marTvis protokolebis TavSi. sicocxlisaTvis SeuTavsebeli wylulovani daavadebebis dros deqsametazonis moxsnis sakiTxi ganxilul unda iqnas protokolis koordinatorTan ara ugvianes 24 saaTis ganmavlobaSi.

deqsametazonis xangrZlivi miRebisas xSiria hiperglikemia gansakuTrebiT, asparaginazasTan kombinaciaSi. glikemia unda kontrolirdebodes mTlianad II fazis dros. steroiduli diabeti unda imarTos insuliniT. Sesabamisad gagrZeldes deqsametazonis miReba. iseve rogorc prednizoloni, wonis mateba siTxis SekavebiT hipertenziiTa an hipertenziis gareSe xSirad Tan axlavs deqsametazonur Terapias. mas raime specifiuri marTva ar Wirdeba, Tumca hipertenziuri sindromis SemTxvevaSi gamoyenebul unda iqnas anti-hipertenziuri preparatebi.

xasiaTis Secvla eiforiiT, disforiiT an depresiiT aseve Tan axlavs deqsametazonis miRebas. pacients aseve SeiZleba gamouvides mZime, paranoiduri fsiqozuri reaqciebi da depresia Tavis mkvlelobis mcdelobiT. am SemTxvevaSi aucilebelia fsiqiatris konsultacia da Sesabamisi Terapiis daniSvna.

31

mZime garTulebebi ufro xSirad Tan axlavs deqsametazonis moxsnas da igi SeiZleba gamoxatul iqnes nivTierebaTa cvlis moSliT, eleqtrorituli disbalansiT, an Tirkmelzeda jirkvlis ukmarisobis klinikuri niSnebiT. aseT SemTxvevaSi pacienti saWiroebs eqimis mudmiv meTvalyureobas, sasicocxlo funqciebis eleqtrolituri da bioqimiuri maCveneblebis koregirebiT.

VCR (vinkristini): 1,5mg/m2/dReSi intra-venurad (maqsimaluri doza 2mg) me-8, 15, 22 da 29 dRes. saSualo simZimiT gamoxatuli VCR-Tan asocirebuli neiropaTia ar aris mizezi medikamentis Secvlisa an amoRebisa remisiis induqciis fazidan. im SemTxvevaSi, Tu gamoixata mZime neiropaTia, SemTxveva ganxiluli unda iyos protokolis nacionalur koordinatorTan.

VCR iSviaTad xdeba mizezi antidiurezuli hormonis sekreciis Seusabamobis sindromisa (SIADH sindromi), romelsac Tan axlavs neirotoqsiurobis klinikuri niSnebi da safiqrebelia, rom igi gamowveulia VCR-is toqsiuri zemoqmedebiT hipoTalamusis supra optikur birTvebze. aRniSnuli sindromis marTvis gaidlaini ixileT programis protokolebis nawilSi.

DOX (doqsorubicini): 30mg/m2/dReSi intra-venurad 1 saaTis ganmavlobaSi me-8, me-15, 22-e da 29-e dRes. pirveli da mesame infuziebis win aucilebelia gakeTdes eleqtrokardiograma da eqokardiografia. im SemTxvevaSi, Tu gamovlinda gulis dazianebis niSnebi (EF <35% an SF <25%), doqsorubicinis doza SesaZloa reducirebul iqnas 50%-iT.

ASP (asparaginaza): 10,000U/m2/dReSi 1 sT-is ganmavlobaSi me-8, me-11, me-15 da me-18 dRes. im SemTxvevaSi, Tu pacients gamoexata hipersensitiuri reaqcia aRniSnul preparatze, rekomendirebulia misi Secvla EG-ASP 1000U/m2/dReSi. ASP-s infuziis win yovelTvis keTdeba testi 10-50 erTeuli an 0,2 erTeuli kilogramze intravenurad 15 wuTis ganmavlobaSi. testis Semdeg velodebiT 30 wuTis ganmavlobaSi. Tu testi dadebiTia ASP unda gadaisxas antihistaminuri da steroiduli preparatebis qolgiT.


ASP-m erTdroulad SeiZleba gamoiwvios Trombozebis ganviTareba da sisxldenebi. Tu pacients ASP-s infuziebis mimdinareobisas aReniSna koagulopaTiisaTvis saxasiaTo klinikuri niSnebi, saWiroa gakeTdes sruli koagulograma da saWiroebis SemTxvevaSi moxdes plazmuri faqtorebis Sevseba. ASP-s erT-erT garTulebas warmoadgens hiperglikemia. amitom, ASP-iT mkurnalobis periodSi saWiroa sisxlsa da SardSi Saqris kontroli. aRniSnuli garTuleba imarTeba insuliniT. im SemTxvevaSi, Tu gamoixata

32

klinikurad – Rebineba, gulisreva, Zlieri sartyliseburi tkivili welis midamoSi, laboratoriulad – lipazasa da aminazas maRali done da radiologiurad – pankreasis struqturis Secvla dadasturebuli pankreatiti, ASP unda amoRebuli iqnas mkurnalobidan.

MTX IT (intra-tekaluri metotreqsati): keTdeba inicialuri centraluri nervuli sistemis dazianebis mqone pacientebSi 1 da me-18 dRes. metotreqsatis dozebi asakobrivia da mocemulia Semdeg cxrilSi:


protokoli II faza II

dawyebis kriteriumebi:

• kargi klinikuri mdgomareoba


• kreatinini asakobrivi normis farglebSia

• sisxlis ujredebis maCveneblebi:leikocitebi =2,000/ì Lgranulocitebi =500/ì LTrombocitebi =50,000/ì L

citozaris blokis dawyebis kriteriumebi:leikocitebi =500/ì LTrombocitebi =30,000/ì L

citozaris blokis gawyveta ar SeiZleba. citozaris bloks Tan unda axldes merkaptopurinis miReba. am ukanasknelis gamotoveba SesaZlebelia blokebs Soris SualedSi ise, rom kumulaciuri doza unda iyos 840 mg/m2

(14 x 60mg/m2).

CPM (ciklofosfamidi): 1000 mg/m2 intra-venurad 1 sT-is ganmavlobaSi 36-e dRes. CPM-is gadasxmis dros unda gatardes Semdegi RonisZiebebi:

• diurezisa da cistitis profilaqtikisTvis intravenurad hidracia 3,000 ml/m2/24 saaTSi (glukoza 5%, fiziologiuri xsnari 0,9%, kaliumis qloridi 4% 30 ml)

• gansazRvre diurezis saaTobrivi da sadReRamiso raodenoba da Seadare miRebuli da gadasxmuli siTxeebis raodenobas. Tu gamoyofili siTxis raodenoba miRebuli siTxis raodenobaze metia 400 ml/m2/12 saaTSi, daiwye furosemidis ineqciebi sawyisi doziT 0,5 mg/kg (maqsimaluri 20 mg) diurezis aRdgenamde.

• uromiteqsani 400 mg/m2 intravenurad 0, 4 da 8 saaTze ciklofosfamis dawyebidan.

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• Tu pacients gamoexata hematuria an mtkivneuli Sardva, saWiroa hidraciis gazrda 4,500-dan 5,000ml/m2/24 saaTSi, furosemidi 0,5 – 1 mg/kg intravenurad yovel 6 saaTSi erTxel. tkivilis SemTxvevaSi gamoiyeneT analgeziuri saSualeba, aseve SegiZliaT gamoiyenoT uromikeqsanis damatebiTi infuzia.


TAG (Tioguanini): 60mg/m2/dReSi oralurad 36-49 dRe saRamos Wamidan 2 saaTis Semdeg rZis gareSe.

ARA-C (citozari): 75mg/m2/dReSi 4 dRis ganmavlobaSi 2 bloki. 38-41 dRe da 45 – 48 dRe.

MTX IT (intratekaluri metotreqsati): 38 – 45 dReze. metotreqsatis dozebi asakobrivia da mocemulia Semdeg cxrilSi:


34

reinduqciuli Terapia mxari II standartuli riskis pacientebisTis

pacientebma, romlebsac mivakuTvnebT standartuli riskis II mxars, unda miiRon reinduqciuri Terapia protokoliT III, romelic Sedgeba 2 fazisagan (III / 1 da III / 2) da igi meordeba orjer 10 kviris intervaliT da maT Soris tardeba dacviTi Terapiis fazebi. Sualeduri dacviTi Terapia iwyeba protokoli III / 1-is damTavrebidan 1 kviris Semdeg da mTavrdeba 1 kviriT adre, vidre daiwyeba III / 2 da moicavs 10 kviras.

Tavis tvinis dasxiveba xdeba dacviTi Terapiis mimdinareobisas pirveli 1,5 – 2,5 kviris ganmavlobaSi da mas Rebuloben mxolod is pacientebi, romlebsac aqvT T ujredovani leikemia an inicialurad aqvs dazianebuli centraluri nervuli sistema.

35

III/1 Sualeduri dacviTi Terapia

III/2

protokoli III

standartuli riskis II mxrisa da maRali riskis I mxris pacientebisaTvis

protokoli III analogiuria Sesabamisi protokolisa, romelic miRebul iqna ALL-BFM-83 swavlebaSi. Tumca, ALL-IC-BFM-2002 Seicavs ciklofosfamids doziT 500mg/m2 me-15 dRes da damatebiT intra-tekalur metotreqsats pirvel dRes im pacientebSi, romelsac inicialurad qonda dazianebuli centraluri nervuli sistema.

dizaini

36

faza III/1

protokolis dawyebis kriteriumebi:

• sruli remisia grZeldeba


• pacients ar aqvs mZime infeqcia

• sisxlis ujredebis maCveneblebi:leikocitebi =2,500/ì Lgranulocitebi =1,000/ì LTrombocitebi =100,000/ì L

DEXA (deqsametazoni): 10mg/m2/dReSi oralurad an intra-venurad gayofili 3 dozaze. 1- 14 dRe. me-15 dRidan iwyeba misi kleba, romelic grZeldeba 9 dRis ganmavlobaSi.

radgan deqsametazoni aris wylulovani daavadebis ganviTarebis riski, saWiroa H2 lokatoris gamoyeneba. Zlierad gamoxatuli gastritis SemTxvevaSi, saWiroa Catardes Sesabamisi RonisZiebebi, romlis marTvis gaidlaini SegiZliaT ixiloT garTulebebis marTvis protokolebis TavSi. sicocxlisaTvis SeuTavsebeli wylulovani daavadebebis dros deqsametazonis moxsnis sakiTxi ganxilul unda iqnas protokolis koordinatorTan ara ugvianes 24 saaTis ganmavlo baSi.

deqsametazonis xangrZlivi miRebisas xSiria hiperglikemia gansakuTrebiT, asparaginazasTan kombinaciaSi. glikemia unda kontrolirdebodes mTlianad II fazis dros. steroiduli diabeti unda imarTos insuliniT. Sesabamisad gagrZeldes deqsametazonis miReba. iseve rogorc prednizoloni, wonis mateba siTxis SekavebiT hipertenziiTa an hipertenziis gareSe xSirad Tan axlavs deqsametazonur Terapias. mas raime specifiuri marTva ar Wirdeba, Tumca hipertenziuri sindromis SemTxvevaSi gamoyenebul unda iqnas anti-hipertenziuri preparatebi.

xasiaTis Secvla eiforiiT, disforiiT an depresiiT aseve Tan axlavs deqsametazonis miRebas. pacients aseve SeiZleba gamouvides mZime, paranoiduri fsiqozuri reaqciebi da depresia Tavis mkvlelobis mcdelobiT. am SemTxvevaSi aucilebelia fsiqiatris konsultacia da Sesabamisi Terapiis daniSvna.

mZime garTulebebi ufro xSirad Tan axlavs deqsametazonis moxsnas da igi SeiZleba gamoxatul iqnes nivTierebaTa cvlis moSliT, eleqtrolituri disbalansiT, an Tikmelzeda jirkvlis ukmarisobis klinikuri niSnebiT. aseT SemTxvevaSi pacienti saWiroebs eqimis mudmiv meTvalyureobas, sasicocxlo funqciebis eleqtrolituri da bioqimiuri maCveneblebis koregirebiT.

VCR (vinkristini): 1,5mg/m2/dReSi intra-venurad. maqsimaluri doza 2 mg 1 da me-8 dRes.

37

VCR SesaZloa dakavSirebuli iyos mZime neiropaTiasTan an iSviaTad xdeba mizezi antidiurezuli hormonis sekreciis Seusabamobis sindromisa (SIADH sindromi), romelsac Tan axlavs neirotoqsiurobis klinikuri niSnebi da safiqrebelia, rom igi gamowveulia VCR-is toqsiuri zemoqmedebiT hipoTalamusis supra optikur birTvebze. aRniSnuli sindromis marTvis gaidlaini ixileT programis protokolebis nawilSi.

DOX (doqsorubicini): 30mg/m2/dReSi intra-venurad 1 saaTis ganmavlobaSi, dRe 1 da 8. pirveli infuziis win aucilebelia gakeTdes eleqtrokardiograma da eqokardiografia. im SemTxvevaSi, Tu gamovlinda gulis dazianebis niSnebi (EF <35% an SF <25%), doqsorubicinis doza SesaZlo reducirebul iqnas 50%-iT.

ASP (asparaginaza): 10,000 U/m2/dReSi intra-venurad 1 sT-is ganmavlobaSi 1, 4, 8, 11 dRes. im SemTxvevaSi, Tu pacients gamoexata hipersensitiuri reaqcia aRniSnul preparatze, rekomendirebulia misi Secvla EG-ASP 1000 U/m2/dReSi. ASP-s infuziis win yovelTvis keTdeba testi 10-50 erTeuli an 0,2 erTeuli kilogramze intravenurad 15 wuTis ganmavlobaSi. testis Semdeg velodebiT 30 wuTis ganmavlobaSi. Tu testi dadebiTia ASP unda gadaisxas antihistaminuri da steroiduli preparatebis qolgiT.


ASP-m erTdroulad SeiZleba gamoiwvios Trombozebis ganviTareba da sisxldenebi. Tu pacients ASP-s infuziebis mimdinareobisas aReniSna koagulopaTiisaTvis saxasiaTo klinikuri niSnebi, saWiroa gakeTdes sruli koagulograma da saWiroebis SemTxvevaSi moxdes plazmuri faqtorebis Sevseba. ASP-s erT-erT garTulebas warmoadgens hiperglikemia. amitom, ASP-iT mkurnalobis periodSi saWiroa sisxlsa da SardSi Saqris kontroli. aRniSnuli garTuleba imarTeba insuliniT. im SemTxvevaSi, Tu gamoixata klinikurad – Rebineba, gulisreva, Zlieri sartyliseburi tkivili welis midamoSi, laboratoriulad – lipazasa da aminazas maRali done da radiologiurad – pankreasis struqturis Secvla, dadasturebuli pankreatiti, ASP unda amoRebuli iqnas mkurnalobidan.

38

Sualeduri dacviTi Terapiis miRebis sqema:

mxari intensiuri Terapiis

elementebi

Sualeduri dacviTi Terapiafazebi fazebis

xangrZlivoba kvirebiT

interpozicia

SR-2 III x 2 1 10 III IIIIR-2 III x 2 2 4 III III IIIHR-1 III x 2 2 4 III III III

HR-2A II x 2 1 4 II II

mogvianebiTi reinduqciis Terapia yovelTvis intensiuria da pacienti xdeba mniSvnelovnad imunokompromisirebuli. Sesabamisad, saWiro xdeba Pneumocystis carinii pnevmoniis profilaqtika da igi mandatorulia yvela pacientisTvis:

• biseptoli trimetoprinze gaangariSebiT 5mg/kg/dReSi gayofili 2 dozad kviraSi 3 dRis ganmavlobaSi. daicaviT, SeZlebisdagvarad, xangrZlivi periodi biseptolisa da metotreqsatis miRebis dReebs Soris. mag., Tu metotreqsats pacienti Rebulobs samSabaTs, merkaptopurini unda miiRos paraskevs, SabaTs, kviras.

• im SemTxvevaSi, Tu pacients aReniSna hipersensitiuroba biseptolze, alternatiuli medikametis saxiT pacientma unda miiRos pentamidini aerozolis saxiT, inhalacia 20-30 wT-is ganmavlobaSi TveSi erTxel. doza misi asakobrivia: <4 w pacientebSi - 150mg/5ml distilirebul wyalSi. pacienti >4w - 300mg/5ml distilirebul wyalSi. bronxospazmis SemTxvevaSi, pacients eniSneba a2 simpatomimetiki pentamidinis Sesxurebamde da Sesxurebis Semdeg.

dacviTi Terapiis medikamentebis dozireba, modificireba da Sesabamisi gamokvlevebis sqema ixileT zogadad dacviTi Terapiis protokolSi.

39

reinduqciuri Terapia IR-2 da HR-2 pacientebisaTvis

aRniSnuli Terapiis ciklebis raodenoba kvirebis mixedviT gamosaxulia Semdeg sqemaze:

2 4 1 4 1 4 1 4 1 4 2kvirebi

reinduqciuli Terapia iwyeba protokol mM/M-is damTavrebidan 2 kviris Semdeg da me-6 dRidan HR-3 blokis Semdeg. igi moicavs protokol III-s, romelic samjer meordeba da maT Soris orjer 4 kviris ganmavlobaSi iniSneba dacviTi Terapia.

maRali riskis Terapiuli strategia

pacientebi, romlebic moTavsdebian maRali riskis jgufSi, mkurnalobas Rebuloben, rogorc qimio, aseve radioTerapiiT. induqciuri Terapiis damTavrebidan 2 kviris Semdeg grZeldeba konsolidacia 3 maRaldozirebuli blokis monacvleobiT (HR-1; HR-2; HR-3). im pacientebis SemTxvevaSi, romlebic inicialuri monacemebiT miekuTvnen maRal risks, miuxedavad imisa, rom isini 33-e dReze SesaZloa iyvnen remisiaSi, mTavrdeba remisiis induqciis orive faza da mxolod mas Semdeg iwyeba konsolidacia. gamonakliss warmoadgenen pacientebi, romlebmac ver miaRwies remisias 33-e dReze. am pacientebSi induqciis meore faza aRar tardeba da iwyeba blokuri Terapia. TiToeuli axali bloki iwyeba wina blokis dawyebidan 2 kviris Semdeg. ALL IC-BFM 2002-is dizainSi naxavT, rom maRali riskis pacientebisaTvis sami Terapiuli blokis Catarebis Semdeg gamoiyofa reinduqciis 2 randomizirebuli mxare. pirveli mxari moicavs Terapiis gagrZelebas samjer III protokolis micemiT, maT Soris, Sualeduri 4 kviriani dacviTi Terapiebis gamoyenebiT. randomizirebuli mkurnalobis meore mxari ki niSnavs, rom pacients unda mieces 3 maRaldozirebuli bloki (HR-1; HR-2; HR-3) Semdgomi II protokolis damatebiT. sxivuri Terapia orive mxarSi savaldebuloa yvela pacientisTvis, magram is pirvel mxarSi tardeba pirveli III protokolis Semdeg, xolo meore mxarSi qimioTerapiis sruli kursis damTavrebis Semdeg. dacviTi Terapia orive mxris pacientebisTvis erTnairia, moicavs 24 Tves da pacients eZleva 6-MP da MTX. maRali riskis pacientebSi dizainSi aseve miTiTebulia Zvlis tvinis gadanergva, romelic SerCeviTia, ar utardeba yvela pacients da misi gadawyveta SesaZlebelia mxolod kvlevis centralur koordinatorTan, Cvens SemTxvevaSi damatebiT ucxoel eqspertebTan (prof. nimaieri, fraiburgi, germania da prof. kingstoni, londoni, didi britaneTi).

40

III Sual. dacv. Terapia


III

Terapiuli elementebi

induqciis Terapiuli protokoli cnobilia protokoli I-is saxiT da dawvrilebiTi informacia mis Sesaxeb ixileT win.

post-induqciuri remisiis statusis gansazRvra

ALL IC-BFM 2002 kvlevaSi remisiis statusis definicia, originaluri BFM kvlevisagan gansxvavebiT, efuZneba citomorfologiur kriteriumebs. sruli remisiis definicia Semdegia:

1. blastebis raodenoba Zvlis tvinSi naklebia normaluri an mcired daqveiTebuli ujredovnebis fonze;

2. pacients ar aReniSneba lokaluri leikemiuri infiltraciebi / masa klinikuri gasinjviTa da radiologiuri kvlevebiT;

3. cerebrospinaluri siTxe ar Seicavs blastebs 33-e dReze Catarebuli lumbaluri punqciis dros.

im SemTxvevaSi, Tu sruli remisia ver iqna miRweuli mkurnalobis dawyebidan 33-e dRes, Zvlis tvinis punqcia unda Catardes rigiT mesame citozaris blokis dawyebamde, anu 52-e dRes. Tu sruli remisia ar iqna dafiqsirebuli, Zvlis tvinis punqcia unda ganmeordes pirveli HR blokis dawyebis win da saWiroebis SemTxvevaSi meore HR blokis win. pacienti, romelic ar uCvenebs srul remisias, meore HR blokis win, klasificirdeba, rogorc qimioTerapiaze aramopasuxe maSin, rodesac vinc miaRwia srul remisias pirveli HR blokis Semdeg, klasificirdeba, rogorc mogvianebiTi mopasuxe qimioTerapiaze. Semdgomi menejmenti zemoT aRniSnuli orive SemTxvevis pacientebis SemTxvevaSi ganixileba protokolis koordinatorTan da ismeba sakiTxi Rerovani ujredis gadanergvaze.

aseTive midgoma xorcieldeba im pacientebSi, romelTac aReniSnebodaT Suasayaris simsivne an inicialuri testikularuli leikemia. rogorc Suasayaris simsivnis zoma, aseve saTesle parkebis zoma Semowmebuli unda iqnes 33-e dReze radiologiuri gamokvlevebiT (eqoskopia, magnetur-rezonansuli da kompiuterul-tomografiuli kvleva). Tu am kvlevebma gamoavlines mniSvnelovani narCeni simsivne (>30% sawyis simsivnesTan SedarebiT), pacienti gadadis maRali riskis mkurnalobis jgufSi.

SeniSvna: rezidialuri narCeni masis simsivnuri xasiaTis gansazRvrisaTvis aseve saWiroa biofsiis gakeTeba da maTSi blasturi ujredebis aRmoCena.

41

ra cvlilebebi aRiniSneba maRali riskis jgufis pacientebis mkurnalobaSi ALL BFM-95 kvlevasTan SedarebiT

1. ASP:• Asp-s damatebiTi doza 25,000 U emateba yvela maRali riskis

bloks me-11 dRes

• infuziis xangrZlivoba 6 saaTis nacvlad Semcirebulia 2 saaTamde

• im SemTxvevaSi, Tu pacients me-11 dRes aReniSneba infeqcia, ASP-s meore doza amoRebul unda iqnas da ar unda iqnas naxmari mogvianebiT, magram SeZlebisdagvarad unda iyos gamoyenebuli axal blokSi.

2. G-CSF–iT Terapia iwyeba yovel blokSi me-11 dRes.

Terapiis regulacia

• Terapiis realizacia unda moxdes, rac SeiZleba swrafad, radgan dozebis intensifikacia erTmniSvnelovnad zrdis prognozis gaumjobesebas. es gansakuTrebiT exeba pirvel sam HR bloks.

• Tu bloks daiwyebT, igi ar unda gawydes.

• nu SeamcirebT medikamentebis dozebs da aseve nu gadawyvetT maTi amoRebis sakiTxs. sicocxlisaTvis SeuTavsebeli garTulebebis SemTxvevaSi acnobeT protokolis centralur koordinators.

• daicaviT intervalebi sxvadasxva medikamentis gadasxmis Soris.

• yoveli blokis win SeamowmeT sxeulis farTi da Sesabamisad SeadgineT medikamentebis dozireba.

HR blokis dawyebis kriteriumebi



• lorwovani garsebi intaqturia

• saSarde gzebi Tavisufalia

• ar aris organuli disfunqciebis saxasiaTo maCveneblebi:1. kreatinini da kreatininis klivensi asakobrivi normis

farglebSia2. ALT da AST x 5 asakobriv normasTan3. bilirubini x 3 asakobriv normasTan

• koagulaciuri parametrebi ar unda iyos garRveuli:1. aPTT x 1.6 asakobriv normasTan2. fibrinogeni x 0.75 asakobriv normasTan3. AT III x 0.75 asakobriv normasTan

• pacients unda aReniSnebodes hemopoeqzis ganaxlkebis niSnebi:1. granulocitebi 200/iL2. Trombocitebi 50,000/iL

• TC 02 saturacia gansazRvruli puls oqsimetriT unda iyos 94%

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G-CSF HR blokebis Semdeg

maRali riskis pacientebis mkurnalobaSi obligatorulad gamoiyeneba Terapia G-CSF-iT (filgrastini) da igi gamoiyeneba yoveli HR blokis Semdeg, Tumca ara protokoli II / III –is Semdeg. G-CSF micemul unda iqnas doziT 5 mg/kg/dReSi kanqveSa an intravenuri infuziebis saxiT. infuzia unda gagrZeldes 4 saaTis ganmavlobaSi. rogorc wesi, G-CSF-is gamoyeneba iwyeba HR blokis dawyebidan 11-e dReze da grZeldeba manam, sanam neitrofilebis raodenoba ar miaRwevs 5,000 iL. aseTi maRali donis miRweva saWiroa imdenad, ramdenadac neitrofilebis raodenoba xSirad ecema G-CSF-is moxsnasTan erTad.

lokaluri, regionaluri Terapia

HR blokebis mkurnalobis procesSi tardeba IT (intratekaluri) Terapia 3 medikamentiT: metotreqsati, citozari da prednizoloni. aRniSnuli Terapia yovelTvis rutinulia da misi Catarebis dros aucilebelia Semdegi pirobebis dacva:

• 1 wlamde asakis bavSvebs an im bavSvebs, romelTac aReniSnebaT gansakuTrebuli SiSi manipulaciebis win da Sesabamisad ver moxdeba maTi fiqsacia manipulaciis dros, unda CautardeT mokle analgezia / anesTezia

• intratekaluri medikamentebis dozireba asakobrivia. ix. Semdegi cxrili:

asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)

0.9% natri-qlori(ml)

<1 6 16 4 1.51 < 2 8 20 6 2.02 < 3 10 26 8 2.53 12 30 10 3.0

• manipulaciis dros miRebuli cerebrospinaluri siTxe aseve gamokvleul unda iqnas Semdegi maCveneblebis mixedviT:

1. bioqimia (saerTo cila, glukoza, laqtati)2. ujredebis daTvla.3. citospinis ujredebis citomorfologiuri Seswavla

• cvlilebebi, Tu ki es ukanaskneli gamovlinda, yovelTvis unda iqnas Zalian zustad dokumentirebuli;

• wyalSi xsnadi prednizolonis derivati (meTilprednizoloni igivea, rac urbazoni an solu-dekortini) ukeTesia iqnas gamoyenebuli, radgan igi amcirebs gverdiTi movlenebis ganviTarebas;

• radgan MTX da ARA-C qimiurad erTmaneTTan araSeTavsebadia, isini ar unda iqnas amoRebuli erT SpricSi. meores mxriv, ARA-C da

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PRED SeTavsebadia da Sesabamisad SesaZlebelia maTi Sereva erT SpricSi. sammagi intratekaluri Terapiisas saWiroa mivyveT Semdeg gaidlains:1. lumbaluri punqciis mandrenian nemsTan erTad aucilebelia

gqondeT sami 5ml Sprici - erTi MTX-Tvis, meore ARA-C sa da PREd-is narevisTvis da mesame fiziologiuri xsnarisTvis;

2. cerebrospinaluri siTxe, romelsac gaaCnia diagnostikuri mniSvneloba yovelTvis aRebul unda iqnas qimiuri preparatebis Seyvanamde;

3. MTX Seyvanili unda iqnas pirvel rigSi da Semdeg Cairecxos fiziologiuri xsnariT asakisaTvis Sesabamisi moculobiT;

4. Semdeg Segvyavs ARA-C-sa da PRED-is narevi aseve fiziologiuri xsnariT Semdgomi CarecxviT;

5. manipulaciis win winaswar daiTvaleT Sesayvani xsnarebis saerTo moculoba. is yovelTvis toli unda iyos miRebuli cerebrospinaluri siTxis moculobisa;

6. pacienti lumbaluri punqciis Semdeg unda iwves 2 saaTi Tavis dabali mdebareobiT.

HR blokebis Tanmxlebi Terapia

1. intravenuri kristaloiduri xsnarebiT hidracia aranakleb 6 dRisa yoveli blokis dros aucilebelia. hidracia xorcieldeba moculobiT: 3,000 ml/m2/24sT-Si. glukoza 5% / natriqlori 0.9% + 90 mmoli/m2 KCI 7.45%. maRaldozirebuli metotreqsatis gadasxmis dReeebSi hidracias emateba natriumis bikarbonati gatutianebis mizniT (ix. metotreqsatis gadasxmis oqmi).

2. hidraciis mimdinareobisas pacients utardeba siTxis balansis monitoringi. im SemTxvevaSi, Tu siTxis balansi metia 400ml/m2/12sT-Si, saWiroa furosemidis micema.

3. leikovoriniT dacva metotreqsatis infuziis dros.4. uroproteqcia uromiteqsaniT (MESNA) ciklofosfamidis infuziebis

dros.5. toqsiuri keratokoniuqtivitis profilaqtikisaTvis deqsametazonis

Tvalis wveTebis gamoyeneba maRal dozirebuli ARA-C-is infuziebis dros.

6. neirotoqsiurobis riskis Semcirebis TvalsazrisiT vitamini B6

infuziebi maRaldozirebuli ARA-C-s gamoyenebis dros.7. Rebinebis sawinaaRmdego efeqturi Terapia HT3 blokatorebis

standartuli medikamentebis gamoyenebiT.8. vitaluri funqciebis monitoringi yoveli blokis mimdinareobis

dros.

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bloki HR-1

dizaini

bloki HR-1 iwyeba induqciis 1 an 2 fazis Semdeg da misi dawyebisTvis aseve pacienti unda akmayofilebdes zogadad im kriteriumebs, romlebic ukve ganvixileT maRali riskis Terapiis dawyebis dros.

DEXA (deqsametazoni) – 20 mg/m2/dReSi oralurad an intravenurad gayofili 3 dozaze 1-5 dRe.

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VCR (vinkristini) – 1.5mg/m2 (maqsimaluri doza 2mg) 1 da 6 dRes. ALL BFM 95-Tan SedarebiT protokol I-is orive faza gamoiyeneba maRali riskis pacientebSi. Sesabamisad, HR-1 bloksa da induqciis fazaSi gamoyenebul vinkristins Soris xangrZlivi Sualedi amcirebs vinkristiniT gamowveul neiropaTias. vinkristinis pirveli doza pacients eZleva 1 saaTiT adre metotreqsatis dawyebamde. vinkristinis meore doza sasurvelia gamoyenebul iqnas 12 saaTiT adre hepatotoqsiuri asparaginazas gadasxmamde, rac amcirebs vinkristiniT gamowveul neirotoqsiurobas, radgan am periodSi igi srulad axerxebs organizmidan gamoyofas.

HD MTX (maRaldozirebuli metotreqsati) – 5,000mg/m2/dReSi 24 saaTis ganmavlobaSi pirvel dRes. maRaldozirebuli metotreqsatis gadasxmis oqmi ixileT m/M protokolis aRweraSi.

CPM (ciklofosfamidi) – 200mg/m2/dReSi 1 saaTis ganmavlobaSi 2- 4 dRe. ciklofosfamidi sumarulad pacients eZleva 5 doza yovel 12 saaTSi erTxel da iwyeba maRaldozirebuli metotreqsatis damTavrebidan 7 saaTis Semdeg. adekvaturi diurezis / hemoragiuli cistitis profilaqtikis mizniT pacients intravenurad utardeba hidracia 3,000ml/m2/24sT-Si siTxis balansis 12 saaTiani infuziis kontroliT. hidracia alkalinizaciiT, romelic Tan axlavs maRaldozirebuli metotreqsatis gadasxmas, pirveli 41 saaTis ganmavlobaSi aseve gadafaravs ciklofosfamidis Tanmxleb hidracias, ris Semdegadac pacients eZleva infuzia natriumis bikarbonatis gareSe. aRniSnuli hidraciuli Terapia ukve ucvlelad gagrZeldeba me-6 dRemde da aseve, Tavis mxiriv, gadafaravs maRaldozirebuli citozaris Tanmxleb infuzias. zemoaRniSnuli dozis ciklofosfamidis xmarebis dros MESNA gamoiyeneba 70mg/m2 doziT.

Tu pacients gamoexata hematuria an mtkivneuli Sardva, saWiroa hidraciis gazrda 4,500-dan 5,000ml/m2/24 saaTSi, furosemidi 0,5 – 1 mg/kg intravenurad yovel 6 saaTSi erTxel. tkivilis SemTxvevaSi gamoiyeneT analgeziuri saSualeba, aseve SegiZliaT gamoiyenoT uromikeqsanis damatebiTi infuzia.


HD ARA-C (citozari) – 2,000mg/m2 intravenurad 3 saaTis ganmavlobaSi me-5 dRes. aRniSnuli doza pacients eZleva 12 saaTSi erTxel. toqsiuri keratokoniuqtivitis prevenciis mizniT pacients eniSneba Tvalebis higiena deqsametazonis Semcveli Tvalis wveTebiT. TiToeul TvalSi ewveTeba TiTO wveTi samjer dReSi aranakleb 2 dRisa citozaris damTavrebidan. maRadozirebuli citozariT gamowveuli neirotoqsiurobis prevenciis mizniT saWiroa B6 vitaminis maRali dozebiT gamoyeneba: 150mg/m2

intravenurad yovel 12 saaTSi erTxel citozaris infuziamde 0,5

46

saaTiT adre aranakleb 2 dRisa citozaris dawyebidan. maRadozirebuli citozaris infuziis dros neirotoqsiurobis simptomebis gamosavlenad guldasmiT dakvirveba obligatorulia. Tu pacients gamoexata nistagmi an ataqsia, infuzia unda Sewydes. Tu aRniSnuli simptomebi ar gaqra an xelaxla gamovlinda citozaris infuziis ganaxlebisas, medikamenti amoRebuli unda iqnas samudamod. sxva SemTxvevaSi miviRebT purkinies ujredebis Seuqcevad dazianebas.

ASP (E.coli-L-asparaginase) – 25,000 U/m2 intravenurad 2 saaTis ganmavlobaSi me-6 da me-11 dRes. . ASP-s infuziis win yovelTvis keTdeba testi 10-50 erTeuli an 0,2 erTeuli kilogramze intravenurad 15 wuTis ganmavlobaSi. testis Semdeg velodebiT 30 wuTis ganmavlobaSi. Tu testi dadebiTia ASP unda gadaisxas antihistaminuri da steroiduli preparatebis qolgiT.


im SemTxvevaSi, Tu pacients aReniSna mZime alergiuli reaqcia E.coli-L-asparaginase-ze, rekomendirebuliaPpegasparaginazes (Oncaspar) gamoyeneba Semdegi doziT: 1,000 U/m2 erT saaTiani infuziiT erTxel mxolod me-6 dRes. alternatiulia meore preparati ErwinaseEdoziT 10,000 U/m2/dReSi intramuskularulad yovel meore dRes: me-6, me-8, me-10, me-12, me-14, me-16 dReebze. L-asparaginase-s sxva gverdiTi movlenebi da misi Sesabamisi marTviTi RonisZiebebi ixileT protokol I-Si.

MTX/ARA-C/PRED IT: intratekaluri metotreqsati, citozari da prednizoloni keTdeba metotreqsatis dawyebidan 1 saaTis Semdeg. dawvrilebiTi informacia ixileT lokaluri regionaluri Terapiis TavSi.

47

bloki HR-2

dizaini

aRniSnuli Terapiuli elementi Tan axlavs yvela maRali riskis pacientis konsolidaciur mkurnalobas iseve, rogorc HR-2 mxris pacientebisaTvis gankuTvnil reinduqcias. HR-2, rogorc wesi, iwyeba HR-1 damTavrebidan me-6 dRes da misi dawyebis kriteriumebi identuria HR-1 dawyebis kriteriumebisa, magram damatebiT moicavs kardiotoqsiurobis gamovlenas da damatebiTi kriteriumis saxiT gamoiyofa eqokardiografiuli kriteriumebi:

SF asakobrivi normis farglebSia.EF > 35%.ixileT HR-2 blokis dizaini.

48

DEXA (deqsametazoni) - 20 mg/m2/dReSi oralurad an intravenurad gayofili 3 dozad, 1-5 dRe.

HD MTX (maRaldozirebuli metotreqsati) – 5,000mg/m2/dReSi 24 saaTis ganmavlobaSi pirvel dRes. maRaldozirebuli metotreqsatis gadasxmis oqmi ixileT m/M protokolis aRweraSi.

MTX/ARA-C/PRED IT: intratekaluri metotreqsati, citozari da prednizoloni keTdeba metotreqsatis dawyebidan 1 saaTis Semdeg. dawvrilebiTi informacia ixileT lokaluri regionaluri Terapiis TavSi.

• negatiuri centraluri nervuli sistemis pacientebSi is keTdeba mxolod erTxel pirvel dRes metotreqsatis dawyebamde 1 saaTiT adre.

• pozitiur centraluri nervuli sistemis pacientebSi is keTdeba orjer: 1 da me-5 dRes.

ASP (E.coli-L-asparaginase) – 25,000 U/m2 intravenurad 2 saaTis ganmavlobaSi me-6 da me-11 dRes. ASP-s infuziis win yovelTvis keTdeba testi 10-50 erTeuli an 0,2 erTeuli kilogramze intravenurad 15 wuTis ganmavlobaSi. testis Semdeg velodebiT 30 wuTis ganmavlobaSi. Tu testi dadebiTia ASP unda gadaisxas antihistaminuri da steroiduli preparatebis qolgiT.


im SemTxvevaSi, Tu pacients aReniSna mZime alergiuli reaqcia E.coli-L-asparaginase-ze, rekomendirebuliaPpegasparaginazes (Oncaspar) gamoyeneba Semdegi doziT: 1,000 U/m2 erT saaTiani infuziiT erTxel mxolod me-6 dRes. alternatiulia meore preparati ErwinaseEdoziT 10,000 U/m2/dReSi intramuskularulad yovel meore dRes: me-6, me-8, me-10, me-12, me-14, me-16 dReebze. L-asparaginase-s sxva gverdiTi movlenebi da misi Sesabamisi marTviTi RonisZiebebi ixileT protokol I-Si.

VDS (vindezini) – 3mg/m2/dReSi (maqsimaluri doza 5 mg) intravenurad neli nakadiT orjer 1 da 6 dRes. vindezinis neirotoqsiurobis riskis Semcirebis mizniT sasurvelia misi gamoyeneba asparaginazas infuziidan 12 saaTis Semdeg me-6 dRes.

SeniSvna: aRniSnuli preparati standartulia HR blokebSi, magram vinaidan igi saqarTveloSi ar aris daregistrirebuli da aseve mis Semotanas ar uzrunvelyofs germanuli mxare, qarTvel pacientebs alternatiulad ukeTdebaT vinskristini 1,5mg/m2/dReSi erTxel. sasurvelia originaluri preparatis (vindezinis)

49

gamoyeneba, radgan vinkristiniT Canacvlebis SemTxvevaSi qarTveli pacientebis umravlesobas ubrundebaT neirotoqsiurobis niSnebi.

IFO (ifosfamidi) – 800mg/m2/dReSi intravenurad 1 saaTis ganmavlobaSi 2-4 dReebSi. aRniSnuli doza pacients eZleva xuTjer 12 saaTSi erTxel da pirveli doza iwyeba maRaldozirebuli metotreqsatis damTavrebidan 7 saaTis Semdeg. ifosfamidis Tanmxlebi infuzia da garTulebebis marTva identuria ciklofosfamidis infuziisa. ixileT ciklofosfamidis gadasxmis oqmi HR-1-Si.

SeniSvna: zemoaRniSnuli teqnikuri mizezebis gamo qarTvel pacientebs ifosfamidis nacvlad Terapia utardebaT ciklofosfamidiT 200mg/m2 doziT, rac erTmniSvnelovnad amcirebs medikamentis efeqturobas, ris gamoc aseve sasurvelia gamoyenebul iqnas ifosfamidi.

DNR (daunorubicini) – 30mg/m2 intravenurad 24 saaTis ganmavlobaSi me-5 dReze. daunorubicinis win, rogorc aRvniSneT, aucilebelia exokardiografiuli kriteriumebis Seswavla da, Tu individualuri pacientis SemTxvevaSi miRebuli monacemebi ar akmayofilebs aRniSnul kriteriumebs, protokolis koordinatorTan SeTanxmebiT SesaZloa misi sqemidan amoReba.

SeniSvna: qarTvel pacientebSi daunorubicinis nacvlad ixmareba doqsorubicini, romelic gacilebiT kardiotoqsiuria da aseve maRali riskia hemoragiuli sindromis gamowvevisa. aRniSnuli mizezebis gamo aseve sasurvelia originaluri preparatis -daunorubicinis gamoyeneba.

50

bloki HR-3

es Terapiuli elementi aris yvela maRali riskis pacientis konsolidaciis nawili iseve, rogorc HR-2 mxris pacientebisaTvis gankuTvnili reinduqciuli Terapiisa. is iwyeba HR-2 blokis damTavrebidan me-6 dReze. dawyebis kriteriumebi identuria HR-1 blokis dawyebis kriteriumebisa.

dizaini

DEXA (deqsametazoni) - 20 mg/m2/dReSi oralurad an intravenurad gayofili 3 dozaze 1-5 dRe.

ASP (E.coli-L-asparaginase) – 25,000 U/m2 intravenurad 2 saaTis ganmavlobaSi me-6 da me-11 dRes. ASP-s infuziis win yovelTvis keTdeba testi 10-50 erTeuli an 0,2 erTeuli kilogramze intravenurad 15 wuTis ganmavlobaSi. testis Semdeg velodebiT 30 wuTis ganmavlobaSi. Tu testi dadebiTia ASP unda gadaisxas antihistaminuri da steroiduli preparatebis qolgiT.

51


im SemTxvevaSi, Tu pacients aReniSna mZime alergiuli reaqcia E.coli-L-asparaginase-ze, rekomendirebuliaPpegasparaginazes (Oncaspar) gamoyeneba Semdegi doziT: 1,000 U/m2 erT saaTiani infuziiT erTxel mxolod me-6 dRes. alternatiulia meore preparati ErwinaseEdoziT 10,000 U/m2/dReSi intramuskularulad yovel meore dRes: me-6, me-8, me-10, me-12, me-14, me-16 dReebze. L-asparaginase-s sxva gverdiTi movlenebi da misi Sesabamisi marTviTi RonisZiebebi ixileT protokol I -Si.

MTX/ARA-C/PRED IT: keTdeba me-5 dRes. intratekaluri punqciis da intratekaluri Terapiis gaidlaini ixileT lokaluri regionaluri Terapiis TavSi.

HD ARA-C (maRaldozirebuli citozari) – 2,000mg/m2 intravenurad sami saaTis ganmavlobaSi pirvel da meore dRes. aRniSnuli doza pacients eZleva oTxjer yovel 12 saaTSi erTxel. toqsiuri keratokoniuqtivitis prevenciis mizniT pacients eniSneba Tvalebis higiena deqsametazonis Semcveli Tvalis wveTebiT. TiToeul TvalSi ewveTeba TiTO wveTi samjer dReSi aranakleb 2 dRisa citozaris damTavrebidan. maRadozirebuli citozariT gamowveuli neirotoqsiurobis prevenciis mizniT saWiroa B6

vitaminis maRali dozebiT gamoyeneba: 150mg/m2 intravenurad yovel 12 saaTSi erTxel citozaris infuziamde 0,5 saaTiT adre aranakleb 2 dRisa citozaris dawyebidan. maRadozirebuli citozaris infuziis dros neirotoqsiurobis simptomebis gamosavlenad guldasmiT dakvirveba obligatorulia. Tu pacients gamoexata nistagmi an ataqsia, infuzia unda Sewydes. Tu aRniSnuli simptomebi ar gaqra an xelaxla gamovlinda citozaris infuziis ganaxlebisas, medikamenti amoRebuli unda iqnas samudamod. sxva SemTxvevaSi miviRebT purkinies ujredebis Seuqcevad dazianebas.

intravenuri hidracia aRniSnul blokSi, wina blokebis msgavsad, iwyeba pirvel dRes da grZeldeba 6 dRis ganmavlobaSi. hidracia mimdinareobs 3,000ml/m2/24sT-Si moculobiT da Sedgeba: glukoza 5% / natriqlori 0,9% + 90 mmoli/m2/24 sT-Si KCL 7,45%. siTxis balansis 12 saaTiani monitoringiT da aucileblobis SemTxvevaSi furosemidis gamoyenebiT.

VP-16 (etopozidi) – 100mg/m2 intravenurad 1 saaTis ganmavlobaSi 3-5 dReebSi. aRniSnuli doza pacients eZleva xuTjer yovel 12 saaTSi erTxel. medikamenti ixsneba 0,9% fiziologiur xsnarSi ganzavebiT: 1 : 50.

gafrTxileba: etopozidis gadasxmisas pacients SeiZleba aReniSnos ariTmia alergiuli reaqciebi anafilaqsiuri Sokis

52

CaTvliT, bronxospazmi, ris gamoc pacienti saWiroebs eqimis dakvirvebas aranakleb 5 saaTisa infuziis Semdeg.

53

reinduqciuri Terapia maRali riskis pacientebisaTvis

reinduqciuri Terapia maRali riskis I da II mxris pacientebisaTvis

pacientebi, romlebic miekuTvnebian saSualo riskis II mxars da is pacientebi, romlebic ganekuTvnebian maRali riskis I mxars, reinduqciur Terapias Rebuloben 3 protokol III Terapiuli elementebis saxiT. TiToeuli maTgani grZeldeba 4 kviris ganmavlobaSi da maT Soris orjer tardeba Sualeduri dacviTi Terapia oraluri merkaptopurinisa da metotreqsatis miRebiT. Sualeduri dacviTi Terapiebic, Tavis mxriv, grZeldeba 4 kviris ganmavlobaSi. aucilebelia mxedvelobaSi miviRoT gansxvaveba saSualo riskis II mxrisaTvis gankuTvnil da maRali riskis I mxris Terapiebs Soris: profilaqtikuri kranialuri dasxiveba utardebaT: 1. saSualo riskis II mxris pacientebs mxolod T-ujredovani leikemiis formebis SemTxvevaSi; 2. yvela maRali riskis mqone pacients, romelTac gaaCniaT centraluri nervuli sistemis ½ statusi.

yvela SemTxvevaSi, pacientebi, romelTac aqvT inicialurad pozitiuri centraluri nervuli sistemis statusi 3, Rebuloben kranialur dasxivebas samkurnalo dozebiT.

reinduqciuri Terapiis sqema zemoaRniSnuli pacientebisaTvis ixileT Semdeg figuraze:

dasxiveba:IR-T ALL,HR,yvela c.n.s.+

2 4 1 4 1 4 1 4 1 4 2kvireebi

ixileT protokoli III-s dizaini.

54

Sual. dacv. Terapia


IIIIII

Sualeduri dacviTi Terapiis sqema:

56

X X X X

sisxlis saerTo analizi

MTX p.o. 20mg/m2/kviraSi erTxel

6-MP p.o. 50mg/m2/dReSi 1-28 dRe

kvirebi 1 2 3 4

reinduqciuri Terapia maRali riskis II mxris pacientebisaTvis

aRniSnuli pacientebisaTvis reinduqciuri Terapia moicavs 3 blokis HR-1, HR-2, HR-3-is monacvleobas Semdgomi protokol II-is micemiT. ix. sqema:

prof. kr. dasxiveba 12 grei

G-CSF G-CSF G-CSF G-CSF Ter. kr. dasxiveba 12/18 grei

2 1 2 1 2 1 3 7 2

dacviTi Terapia SR, IR, HR pacientebisTvis

qimioTerapiis damTavrebis Semdeg pacientebTan iwyeba dacviTi Terapia 6-MP da MTX-iT. Terapiis mTliani xangrZlivoba induqciis kursis dawyebidan grZeldeba 104 kviris (24 Tvis) ganmavlobaSi yvela pacientisaTvis, romelTac utardeba mkurnaloba ALL-IC BFM 2002-iT. mTliani Terapiis Sejamebuli sqema ixileT Semdeg cxrilSi:

mxareint. Terapia(kvirebi)

dacviTi Terapia(kvirebi)

Terapiis mTliani xangrZlivoba(kvirebi)

SR-1 30 74 104SR-2 43 61 104IR-1 30 74 104IR-2 47 57 104HR-1 46 58 104HR-2A 42 62 104HR-2B 41 63 104

dacviT Terapiaze yvela pacienti Rebulobs oralurad yoveldRiur 6-MP-s da kviraSi erTxel MTX-s. standartuli doza 6-MP da MTX-isa identuria yvela pacientisaTvis.

MP (6 merkaptopurini) – 50mg/m2/dReSi p.o. erTxel dReSi saRamos

MTX (metotreqsati) – 20mg/m2 p.o. kviraSi erTxel (kviris erTsa da imave dRes) saRamos.

57

HR

2’

II

HR

1’

HR

3’

6-MP-isa da MTX-is doza regulirdeba leikocitebis raodenobis mixedviT:

leikocitebi i/L

<1,000 1,000 – 2,000 >2,000 – 3,000 >3,000

limfocitebi i/L

<300

MP / MTX % 0 50 100 150 50

ix. dacviTi Terapiis dizaini

dacviTi terapiis dawyebis kriteriumebi:


• pacients ar aqvs mZime infeqcia

• hematologiuri maCveneblebi:leikocitebi: 1000 i/Lgranulocitebi 200 i/LTrombocitebi 50,000i/L

daciTi Terapiis gawyveta xdeba mxolod Semdeg SemTxvevaSi:

58

• leikocitebi < 1,000 i/L• infeqciebi: RviZlis toqsiurobis III xarisxi: ALT/AST > 5 x asakobriv

normaze; bilirubini > 3 x asakobriv normaze• xangrZlivi diarea

• cvlilebebi filtvebSi klinikurad an radiologiurad (MTX-iT gamowveuli pnevmoniti)

mogvianebiT reinduqciis Terapia yovelTvis intensiuria da pacienti xdeba mniSvnelovnad imunokompromisirebuli. Sesabamisad saWiro xdeba Pneumocystis carinii pnevmoniis profilaqtika da igi mandatorulia yvela pacientisTvis:

• biseptoli trimetoprinze gaangariSebiT 5mg/kg/dReSi gayofili 2 dozad kviraSi 3 dRis ganmavlobaSi. daicaviT SeZlebisdagvarad xangrZlivi periodi biseptolisa da metotreqsatis miRebis dReebs Soris. mag., Tu metotreqsats pacienti Rebulobs samSabaTs, merkaptopurini unda miiRos paraskevs, SabaTs, kviras.

• im SemTxvevaSi, Tu pacients aReniSna hipersensitiuroba biseptolze, alternatiuli medikametis saxiT pacientma unda miiRos pentamidini aerozolis saxiT, inhalacia 20-30 wT-is ganmavlobaSi TveSi erTxel. doza misi asakobrivia: <4w pacientebSi - 150mg/5ml distilirebul wyalSi. pacienti >4w - 300mg/5ml distilirebul wyalSi. bronxospazmis SemTxvevaSi, pacients eniSneba a2 simpatomimetiki pentamidinis Sesxurebamde da Sesxurebis Semdeg.

dacviT Terapiaze myof pacients rutinulad utardeba Semdegi kvlevebi:

• sisxlis saerTo analizi unda Catardes kviraSi erTxel metotreqsatis miRebis dRes da Sesabamisad SeirCes momdevno kviris merkaptopurinisa da metotreqsatis dozireba.

• ALT/AST, bilirubini, albumini, kreatinini da Sardis analizi regularulad Semowmdes yovel 8-12 kviraSi.

• damatebiTi kvlevebi iniSneba mxolod mas Semdeg, rodesac pacientis gasinjvisas eqimi aRmoaCens ama Tu im sistemis dazianebis saxasiaTo klinikur an fizikalur niSnebs.

intratekaluri MTX dacviTi Terapiis dros

pre-B ujredovani pacientebi, romlebic miekuTvnebian SR an IR I mxars, dacviTi Terapiis dros Rebuloben IT MTX-is 4 damatebiT dozas dacviTi Terapiis dawyebidan me-4, me-8, me-12 da me-16 kviras. intratekaluri metotreqsatis dozireba asakobrivia:


pacientebi, romlebic miekuTvnebian pre-B ALL-is standartuli riskis II mxares, iReben IT MTX-is 2 damatebiT dozas me-4 da me-8 kviras.

59

SeniSvna: pacientebi inicialuri centraluri nervuli sistemis dazianebiT, romlebmac ukve miiRes adekvaturi intensiuri Terapia + kranialuri dasxivebiT, dacviT Terapiaze IT MTX-s ar Rebuloben. igive exeba yvela T ujredovan pacients, miuxedavad imisa, Tu romel mxars ganekuTvnebodnen isini.

60

sxivuri Terapia

ALL-BFM-95-Tan SedarebiT ALL IC-BFM 2002 centralur nervul sistemaze orientirebul TerapiaSi moicavs 5 ZiriTad gansxvavebas. es gansxvavebebi exeba IT MTX-is dozebs, raodenobas da sxivur Terapias:

1. centraluri nervuli sistemis (cns) leikemiis definicia gafarTovda da is moicavs izolirebuli retinis CarTvas iseve, rogorc izolirebuli Tavis tvinis nervebis dazianebas, radgan leikemiiT daavadebul pacientebSi diagnozis dasmisas igi ar SeiZleba iyos gamowveuli araleikemiuri procesebiT. cns-is dazianeba am SemTxvevaSi dadebiTad iTvleba maSinac ki, rodesac cerebro spinluri siTxe blastebisagan Tavisufalia.

2. ALL IC-BFM 2002 kvlevis erT-erT mTavar kiTxvas warmoadgens im pacientebis randomizireba, romlebmac miiRes mogvianebiT reinduqciuri Terapia. kiTxvaze pasuxis gasacemad maRali riskis pacientebSi 2 sakontrolo jgufi iyo amorCeuli, romelTa nawili sxivdeba 12/18 greiT, Tumca pacientebi, romlebic <1 w da miiRes mkurnaloba maRali riskis II mxris Tanaxmad, dadebiTi cns-is statusisaTvis, iReben 12 greis, rogorc profilaqtikur dozas, an 12/18 greis, rogorc samkurnalo dozas.

3. maRali riskis pacientebi, romelTac utardebaT Rerovani ujredis gadanergva, iReben neirokraniumis da saTesle parkebis profilaqtikur damatebiT dasxivebas. Tumca, cns-is dazianebisas isini Rebuloben Terapiul lokalur fraqcinirebul dasxivebas erTi kviriT adre mTliani sxeulis dasxivebamde.

4. 2gr/m2 MTX-is sakompensaciod aRniSnul pacientebSi tardeba damatebiTi IT MTX_iT mkurnaloba dacviTi Terapiis dros x4: me-4, me-8, me-12, me-16 kvirebze SR-1, IR-1, BCT-ALL pacientebSi. xolo CR 2, BCP-ALL pacientebSi ki - x2, me-4 da me-8 kviras.

5. SR/IR pacientebi, romelTac aqvT T ujredovani leikemia, konsolidaciuri Terapiis saxiT Rebuloben maRaldozirebul MTX-s. maT aseve unda miiRon Tavis tvinis profilaqtikuri dasxiveba cns-is statusis 1 / 2 SemTxvevaSi maSin, rodesac ALL BFM-95-Si mxolod saSualo riskis pacientebi Rebuloben aseT Terapias. cns-isadmi mimarTuli qimioTerapiis gansxvaveba ALL BFM-95-sa da ALL IC-BFM 2002 Soris ixileT Semdeg cxrilebSi:

c.n.s-is Terapia ALL-BFM -95-is mixedviT

riskis jgufi

sistemuri qimioTerapialokaluri regionaluri

qimioTerapia

HD MTX HD ARA-C #IT MTX† #TIT† #SR 5g/m2/24sT-Si x4 11+(4) 11+(4)MR 5g/m2/24sT-Si x4 11+(4) 11+(4)HR 5g/m2/24sT-Si x4 2g/m2/3sT-Si x12 5+(3) 6+(2) 11+(5)

61

c.n.s-is Terapia ALL IC-BFM -2002-is mixedviT

riskis jgufi

sistemuri qimioTerapialokaluri regionaluri

qimioTerapia

MD/HD MTX HD ARA-C IT MTX†

#TIT†

##

BCP:SR-1BCP:SR-2BCP:IR-1

2g/m2/24sT-Si x4 15+(4) 15+(4)

T: SR-1T: IR-1

5g/m2/24sT-Si x4 11+(4) 11+(4)

T: SR-2 5g/m2/24sT-Si x4 13+(4) 13+(4)BCP: IR-2 2g/m2/24sT-Si x4 15+(5) 15+(5)T: IR-2 5g/m2/24sT-Si x4 15+(5) 15+(5)BCP/T:HR-1 5g/m2/24sT-Si x2 2g/m2/3sT-Si x6 11+(5) 3+(1) 14+(6)BCP/T:HR-2A 5g/m2/24sT-Si x2 2g/m2/3sT-Si x6 9+(6) 3+(1) 12+(7)BCP/T:HR-2B 5g/m2/24sT-Si x4 2g/m2/3sT-Si x12 7+(4) 6+(2) 13+(6)

† intratekaluri metotreqsati da 3 medikamentiT (MTX, ARA-C da PRED) intratekaluri Terapia# damatebiTi intratekaluri dozebi centraluri nervuli sistemis dazianebul pacientebSi (cns statusi 3). es pacientebi Rebuloben Tavis tvinis Terapiul dasxivebas.

dasxivebis winaaRmdeg Cvenebebi

1. <1 w bavSvebi dasxivebas ar Rebuloben; 2. <2 w pacientebi, romelTac utardebaT Rerovani ujredis

gadanergva, ar Rebuloben arc mTeli sxeulis dasxivebas, arc pirveladad dazianebuli areebis lokalur sxivur Terapias;

3. pacientebs, romelTac aReniSneba seriozuli araleikemioduri cns dazianebebi MTX-iT gamowveuli leikoencefalopaTiis CaTvliT, an anamnezSi aReniSnebaT intrakranialuri Trombozebi an sisxlCaqcevebi, ar sxivdebian;

4. pacientebs, romelTac aReniSnebaT Tandayolili qromosomuli sindromebi, aseve ar unda iqnen dasxivebuli. aqve unda gaviTvaliswinoT, rom pirveladi imunodeficitis mqone pacientebi, romelTac TavisTavad aReniSnebaT sistemuri mukozitebi, konsolidaciis dros unda miiRon 1gr/m2 MTX nacvlad 5gr/m2-isa. maT mkurnalobaSi aseve reducirebul an amoRebul unda iqnas iseTi qimiuri preparatebi, rogoricaa ciklofosfamidi, ifosfamidi da vepizidi. reducireba SesaZlebelia 20-80%-mde individualuri tolerantobis mixedviT (Irsfeld H et al. 2000, Seidemann K et al. 1999 & 2000);

5. dasxiveba aseve winaaRmdeg naCvenebia im pacientebSi, romlebsac aReniSnebaT bazalur-ujredovani karcinoma – gorlinis sindromi;

6. dasxivebamde pacients ar unda aReniSnebodes cns infeqciis Tundac erTi simptomi an niSanic ki.

62

dasxivebis dro

sxivuri Terapia pacientebis umravlesobaSi sistemuri qimioTerapiis damTavrebis Semdeg tardeba. Tumca, pacientebSi, romlebic miekuTvnebian HR-2B-s, sxivuri Terapiis Catareba xdeba bolo intensiuri Terapiuli elementis Semdeg (protokoli II). pacientebs, romelTac utardebaT Rerovani ujredis gadanergva, mTliani sxeulis dasxiveba utardebaT gadanergvis wina qimioTerapiis (kondicirebis) paralelurad.

teqnikuri procedurebi

kranialuri dasxiveba unda Catardes maRali energiuli sxivebiT (6 mv) sxivuri aqseleratoris saSualebiT. dasxivebamde dgeba Terapiuli gegma, romelic moicavs:

1. Tavis individualuri niRbis SerCeva da damzadebaж2. sxivis moculobis gansazRvra da misi mimarTulebis dagegmareba

ise, rom SesaZlebeli gaxdes intrakranialuri struqturebis orive – retrobulbaruli areebis da fuZis mTlianad moxvedra sxivur velSi;

3. ZiriTadi yuradReba gadatanil unda iyos dozis homogenurad miwodebaze da mis gavrcelebaze orive mxris kontralateralur velebze;

4. dRiuri doza standartulad aris 1.5 grei da pacienti kviraSi sxivdeba 5 dRis ganmavlobaSi manam, sanam ar Sesruldeba sxivuri Terapiis sumaruli doza.

5. pacientebSi, romelTa asaki 1-2 meryeobs, aucilebelia hiperfraqcionaluri dasxiveba (0.8 grei x2 dReSi an 1.0 grei x2 dReSi aranakleb 6 saaTis Sualedisa).

63

sxivuri Terapiis dozebi, xangrZlivobariskis jgufebis, asakis da cns statusis mixedviT

riskis jgufi:mxare

asaki *

(wlebi)

pCRT: cns statusi 1 an 2† tCRT: cns statusi 3†

dozireba(grei)

vadebidozireba(grei)

vadebi

SR-1 1<2 12‡ pirveli 1.5 kv prot. II-is Semdeg

12 pirveli 1.5 kv prot. II-is Semdeg

2 12‡ pirveli 1.5 kv prot. II-is Semdeg


SR-2 1<2 12‡ pirveli 1.5 kv Sual. dacviTi Terapiis dros

12 pirveli 1.5 kv Sual. dacviTi Terapiis dros

2 12‡ pirveli 1.5 kv Sual. dacviTi Terapiis dros

18 pirveli 2.5 kv Sual. dacviTi Terapiis dros

IR-1 1<2 12‡ pirveli 1.5 kv prot. II-is Semdeg


2 12‡ pirveli 1.5 kv prot. II-is Semdeg


IR-2 1<2 12‡ pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros

12 pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros

2 12‡ pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros


HR-1 1<2 12 pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros


2 12 pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros


HR-2A 1<2 12 pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros


2 12 pirveli 1.5 kv pirveli Sual.dacv. Ter-is dros


64

HR-2B 1<2 12 pirveli 1.5 kv pirveli prot II-is Semdeg

12 pirveli 1.5 kv pirveli prot II-is Semdeg

2 12 pirveli 1.5 kv pirveli prot II-is Semdeg

18 pirveli 2.5 kv pirveli prot II-is Semdeg

† SemTxvevebi definicirebulia, rogorc cns status 2 da es pacientebi iReben damatebiT IT MTX me-18 da 27-e dRes protokoli I dros, magram ara Terapiul dasxivebas. Tumca, SR / IR T ujredovani leikemiis mqone pacientebi da maRali riskis jgufis pacientebi, romlebic ar gadian Rerovani ujredis gadanergvas da aqvT cns statusi 1/2, Rebuloben profilaqtikur dasxivebas.

‡ mxolod T ujredovani leikemiis mqone pacientebi.

* <1 w pacientebi dasxivebas ar Rebuloben.

sxivuri Terapiis gverdiTi movlenebi

1. yvelaze xSir gverdiT movlenas warmoadgens Tavis tkivili. mokle xangrZlivobis deqsametazoni 15 mg/m2/dReSi efeqturia aRniSnuli simptomis mosaxsnelad.

2. apaTia/somnolencia SesaZloa gamovlindes Tavis dasxivebidan 4 – 6 kviris Semdeg. aseTi pacientebi saWiroeben hematologisa da nevrologis dakvirvebas simptomebis moxsnamde. adeqvaturi Zili da sinaTlis sxivebisagan dacva aris damxmare RonisZieba aseT pacientebSi.

3. specifiuri inteleqtualuri deficiti aseve SeiZleba gamovlindes Tavis dasxivebis Semdeg. aseT SemTxvevaSi pacients esaWiroeba fsiqologiuri da pedagogiuri daxmareba.

4. individebi, romlebsac dasxivebamde aReniSnebodaT cerebraluri dazianeba, warmoadgenen riskis jgufs meoradi Tavis tvinis simsivneebis ganviTarebisa. aseTi pacientebi saWiroeben specifiur midgomas sxivuri Terapiis win da mis nacvlad ukeTesia gamoyenebul iqnas intratekaluri metotreqsatebiT mkurnaloba, rogorc alternatiuli gza.

65

qimioTerapiis dros arsebuli da mosalodneli garTulebebis marTva

Sesavali

pediatri-hematologi da onkologi qimioTerapiis dawyebamde srulad unda iyos informirebuli yvela mosalodneli garTulebis marTvis Sesaxeb. Cven SemogTavazebT ZiriTadi garTulebebis Terapiul gaidlainebs, romlebic warmoadgens bazisur samoqmedo gegmas eqimisaTvis. magram masSi cvlilebebis Setana pacientis individuluarobis gaTvaliswinebiT, rasakvirvelia, SesaZlebelia.

Cveni rekomendaciebi ar aris mxolod erTi klinikis an centris gamocdilebaze damyarebuli da mas safuZvlad udevs evropis da amerikis Sesabamisi klinikebis da samecniero centrebis utyuar statistikur meTodebze SemuSavebuli faqtebi.

66

simsivnis mwvave lizisis sindromi

bazisuri aspeqtebi

1. blasturi ujredebis intensiuri lizisi iwvevs ujredSida nivTierebebis masiur gamoyofas sistemur cirkulaciaSi. iseTi ujredSida nivTierebebis, rogoricaa purinis metabolitebi – hipoqsanTini, qsanTini da SardmJava, potasiumi da fosfatebi, gamoTavisufleba pirdapir kavSirSia mwvave lizisis sindromis paTofiziologiasa da klinikur niSnebTan. Tirkmelebi asruleben gadamwyvet rols aRniSnuli nivTierebis eliminaciaSi.

2. laboratoriuli da klinikuri niSnebi da simptomebi mwvave lizisis sindromisa variabeluria da damokidebulia ujredebis daSlis sixSireze, simsivnur masaze, pacientis organoebis funqciaze.

3. aRsaniSnavia, rom mwvave lizisis sindromis WeSmariti gamovlena ar aris cnobili, magram arsebobs faqtorebi, romlebic erTmniSvnelovnad zrdian aRniSnuli sindromis ganviTarebis risks:

• simsivnis tipi: mwvave da qronikuli leikemiebi, simsivnuri limfopoliferaciuli daavadebebi, romlebsac axasiaTebs maRali avTvisebianoba – arahojkinis limfomebi, B ujredovani mwvave leikemia da T ujredovani mwvave leikemia.

• simsivnuri ujredebis maRali mgrZnobeloba antineoplaziuri Terapiis mimarT.

• inicialuri simsivnuri masis da gavrcelebis xarisxi: hiperleikocitozi (leikocitebis raodenoba > 100,000i/L), limfoma – leikemiuri sindromi, Zliergamoxatuli organomegalia, mediastinaluri didi simsivne, abdominaluri an retroperitonialuri simsivnuri masa.

• simsivnuri ujredebis maRali proliferaciuli sixSire.

• laqtadehidrogenaza (LDH) > 1,500

• Sardis gamoyofis Semcireba

• Tirkmlis paTologiebi an obstruqciuli uropaTia

• Tirkmlebis infiltracia simsivnuri ujredebiT

• sxva faqtorebmac SeiZleba moaxdinon mwvave lizisis sindromis provocireba: sefsisi, disiminirebuli intravaskularuli koagulopaTia, nefrotoqsiuri medikamentebis xmareba, aseve im agentebis gamoyeneba, romlebic iwveven hiperkalemiis efeqts.

4. purinuli katabolizmi damokidebulia individis mJava-tutovan wonasworobaze, kerZod ki, pH. ixileT Semdegi cxrili:

67

purinuli metabolitebis xsnadobis limiti pH-is mixedviT

pH Sard-mJava (mg/l) qsanTini (mg/l) hipoqsanTini (mg/l)5.0 150 50 1157.0 2,000 130 1,500

5. purinuli metabolitebi, maRali koncentraciis SemTxvevaSi, kristalebis saxiT gvxvdebian Tirkmlis distalur milakebSi, rac, Tavis mxriv, iwvevs glomerulebis filtraciis sixSiris daqveiTebas Tirkmlis mwvave ukmarisobis ganviTarebiT.

6. aseve fosfatebis SeboWva kalciumTan sabolood kalciumis fosfatis warmoqmniT gvxvdeba, rogorc Tirkmlis milakebSi, aseve mis rbil qsovilSi da Sesabamisad xdeba mizezi nefrokalcinozis, Tirkmlis ukmarisobis an disfunqciis da hipokalcenumis. meores mxriv, maRali proliferaciuli simsivneebis dros mkurnalobamde fosforis done SeiZleba iyos normaluri an dabali, radgan mas intensiurad moixmars axlad warmoqmnili simsivnuri ujredebi.

7. qsanTinisa da Sard-mJavasagan gansxvavebiT, kalciumis fosfatis xsnadoba tutovan garemoSi Zalian dabalia.

8. gansxvavebuli xsnadoba purinuli metabolitebisa da kalciumis fosfatebis sxvadasxva pH-is pirobebSi iZleva rekomendacias, Seiqmnas Sardis pH 7–7.5 im periodSi, rodesac Zalian maRalia mwvave lizisis sindromis ganviTarebis riski (24-48 sT, magram ara didxans, vidre 72-96 sT). ramdenadac es SesaZlebeli SeiZleba iyos, qimioTerapis ukeTesia daiwyos pacientis alkalinizaciis Semdeg. ra Tqma unda, qimioTerapiis micema ar unda dagviandes.

9. hiperkalemia xSiria mwvave lizisis sindromis dros da mas SeuZlia gamoiwvios sicocxlisaTvis saSiSi garTulebebi.

10. cilovani katabolizmis momateba Zalian xSiria pacientebSi diagnozis dros, rac Tavis mxriv, xels uwyobs sisxlis Sardovanas donis gazrdas. Tirkmlis funqciis daTrgunva am SemTxvevaSi vlindeba azotemiiT da Sesabamisad yuradRebas ipyrobs misi klinikuri niSnebi da simptomebi. azotemia ZiriTadad qreba hiperfosfatemiis paralelurad.

11. pacienti antileikemiuri Terapiis dawyebamde saWiroa iqnes dastabilirebuli. im SemTxvevaSi, rodesac Sard-mJava, kaliumi, fosfori an kreatinini qimioTerapiis dawyebamde ukve momatebulia, RonisZiebebi mimarTul unda iqnas metaboluri darRvevebis gamosworebisaken, risTvisac SesaZloa gamoviyenoT pirveli 24 saaTi citoreduqtiuli fazis dawyebamde.

12. yvelaze mniSvnelovan RonisZiebas warmoadgens Sardis gamoyofis maRali donis iniciacia ise, rom Sardis xvedriTi wona 1,010-is farglebSi meryeobdes.

13. pacientTan iwyeba Sesabamisi hidratacia diuretikebis paraleluri gamoyenebiT da im SemTxvevaSi, Tu Sardis gamoyofa Semcirda gazrdis nacvlad, eqimi droulad emzadeba dializis dasawyebad.

hiperurikemiis menejmenti

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hiperurikemia definicirdeba maSin, rodesac plazmis Sard-mJavas done aris 7 mg% (420 mmoli/l). medikamentebi, romlebic ixmareba hiperurikemiis kontrolisaTvis, aris alopurinoli. bolo dros rekomendirebuli medikamentia rasburikaze (fasturteki).

alopurinoli

1. alopurinoli ganicdis daJangvas RviZlis qsanTinoqsidazes mier da gadadis oqsipurinolSi, romlis aqtiuroba, rogorc inhibiciuri enzimis, ufro maRalia, ris Sedegadac xdeba misi plazmaSi akumulacia da SardiT qsanTinisa da hipoqsanTinis masiuri eqskrecia. alopurinolis naxevargamoyofis periodi 300mg dozis SemTxvevaSi aris 1,3 sT misi peroraluri micemisas da 1,2 sT intravenurad xmarebisas, roca oqsipurinolisaTvis is aris daaxloebiT 24 sT da damokidebulia dozaze (100/300mg).

2. alopurinolis rekomendirebuli doza peroraluri an intravenuri aris 200-400mg/m2/dReSi (300mg/m2/dReSi = 10mg/kg/dReSi). doza unda gadanawildes 3 miRebaze, xolo medikamentis miRebis xangrZlivoba aris 3-8 dRe. alopurinolis doza unda SeirCes da ganisazRvros purikemiis donisa da Tirkmlis funqciis gaTvaliswinebiT.

alopurinolis dozireba Tirkmlis funqciis korelaciasTan

Tirkmlis filtraciis sixSire = klirensi

doza(%)

>20 10020 50–66 10 10-25-33<3 10-25

3. intravenuri alopurinoli (apurini, aloprimi) gamoiyeneba im SemTxvevaSi, rodesac pacienti ver Rebulobs oralur medikamentebs. intravenuri formulacia unda gaixsnas 5% glukozaSi an 0.9% fiziologiur xsnarSi koncentraciiT 6mg/ml. gaxsnili medikamenti stabiluria 10 saaTis ganmavlobaSi, ar unda gaiyinos. medikamenti SeuTavsebadia natriumis bikarbonatTan.

4. pacientebi alopurinolis mimarT ZiriTadad tolerantuli arian. magram Zalian iSviaTad (1%) SeiZleba ganviTardes kanis gardamavali gamonayari an urtikaria. aseve gamovlindes Tavis tkivili, Rebineba, diarea.

5. im pacientebSi, visac citoreduqtiuli qimioTerapiuli mkurnalobis dawyebamde aReniSnebaT Tirkmlis ukmarisobis niSnebi an anamnezSi aReniSnebaT Tirkmlis qronikuli daavadebebi, alopurinoli dawyebul unda iqnas qimioTerapiamde.

rasburikaze (fasturteki)

1. rasburikazes gamoyeneba ganapiroba misma ramodenime ufro efeqturma Tvisebam, vidre es alopurinols gaaCnia:

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- mas gaaCnia ufro swrafi urikulizuri moqmedeba;- qsanTinisa da hipoqsanTinis akumulacia nefropaTiis

ganviTarebiT ufro naklebad xdeba rasburikazes gamoyenebisas;

- misi gamoyenebis SemTxvevaSi alkalinizacia ar aris aucilebeli, rac Tavis mxriv, prevencias uwevs mniSvnelovani metaboluri alkalozis ganviTarebas, aseve xels uwyobs kalciumis fosfatis xsnadobas da misi Tirkmlidan Seuyovnebliv gamoyofas;

- misi gamoyenebis dros ar aris gamovlenili medikamentTan interaqciuri efeqtebi.

2. rasburikaze saWiroa gamoyenebul iqnas im pacientebSi, romlebic warmoadgenen mwvave lizisis sindromis ganviTarebis maRal risks.

3. medikamenti gamodis liofizirebuli xsnaris saxiT, romelic inaxeba 2-80 pirobebSi. medikamenti xmarebis win ixsneba 50 ml fiziologiur xsnarSi da maSinve iwyeba misi gadasxma doziT 0.15 an 0.20mg/kg 30 wT-is ganmavlobaSi 24 saaTSi erTxel da infuzia grZeldeba 5-7 dRis ganmavlobaSi.SeniSvna: medikamentis gadasxmisas gamoiyeneba calke vena. medikamenti ar unda gaixsnas an Seerios deqstrozas.

4. gverdiTi movlenebis saxiT pacients SeiZleba gamouvlindes Tavis tkivili, cxeleba, gulisreva, Rebineba, qavili, saxis an tuCebis SeSupeba, respiratoruli diskomforti an distre-sindromis ganviTareba. aRniSnuli garTuleba nanaxia pacientebis mxolod 2 %-Si. unda gaviTvaliswinoT, rom pacients, romelsac anamnezSi aqvs glukoza-6-fosfatdehidrogenazas deficiti, ar miecema aRniSnuli preparati.

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mwvave lizisis sindromis prevencia

1. eliminacia an minimumamde dayvana yvela im faqtoris, romelmac SeiZleba gamoiwvios aRniSnuli sindromi;

2. alopurinoli 10mg/kg/dReSi oralurad an intravenurad gayofili 3 dozaze 3-5 dRis ganmavlobaSi;

3. intravenuri hiperhidratacia: 3,000 – 5,000ml/m2/dReSi 5% glukozisa da 0,45% fiziologiuri xsnariT;

4. xsnarebs ar daematos kaliumis qloridi. hipokalemia nu SegaSinebT;

5. intravenuri gatutianeba Sardis, natriumis bikarbonati 40–80 mmoli/l (100-200 mmoli/m2/dReSi);

6. Terapiis monitoringi da regulacia:- muclis Rrus ultrabgeriTi gamokvleva:

? Tirkmlebis infiltracia blasturi ujredebiT? saSarde gzebis obstruqcia simsivnuri ujredebiT? kalci-fosfatebiT gamowveuli nefrofatia? saSarde gzebis anomaliebi

- balansis kontroli: gamoyofili = miRebuls gamoklebuli respiratoruli

- gaakontroleT sxeulis wona x2 dReSi- daaregulire Sardis gamoyofa 100-250 ml/m2/sT-Si - araadeqvaturi gamoyofis SemTxevvaSi furosemidi

intravenurad 1-10 mg/kg/dReSi (gafrTxileba: ar moxdes siTxis cirkulatoruli gadaWarbeba)

- awarmoeT natriumis bikarbonatis miwodebis kontroli: Sardis optimaluri pH 7.0 – 7.5

- SeinarCuneT Sardis xvedriTi wona < an = 1,010- laboratoriuli testebidan isazRvreba leikocitebi,

kalciumi, fosfori, Sard-mJava da kreatinini yovel 12 saaTSi erTxel. kritikuli SemTxvevebisas aRniSnuli maCveneblebi isazRvreba ufro xSirad.

7. mwvave lizisis sindromis riskis gamovlenisas daiwyeT fasturtekis gamoyeneba 0,15-0,20 mg/kg/24sT-Si naxevarsaaTiani infuziiT 5-7 dRis ganmavlobaSi. rogorc ukve zemoT aRvniSneT, am dros gatutianeba aRar aris saWiro.

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mwvave lizisis sindromis Terapia

prevenciuli RonisZiebebi faqtiurad warmoadgens ukve Camoyalibebuli lizisis sindromis baziss, magram Terapia unda gaZlierdes da yuradReba mieqces sicocxlisaTvis saSiSi garTulebebis drouli diagnostikiTa da marTviT.

hiperurikemia

hiperurikemiis menejmenti iwyeba hiperhidrataciiT 5,000ml/m2/24sT-Si Sardis pH-is 7.0 – 7.5 farglebSi SenarCunebiT. sxva danarCeni RonisZiebebi igivea, rac prevenciis SemTxvevaSi. ix. zemoT.

hiperkalemia

RonisZiebebi saswrafoa da ar iTvaliswinebs mocdis taqtikas. kaliumis donis mixedviT RonisZiebebi iyofa Semdegnairad: Tu kaliumis done ar aRemateba 6 mmoli/l, pacienti mzaddeba dializisaTvis, xolo Tu misi done aris 7 mmoli/l, iwyeba saswrafo hemodializi.

urgentuli RonisZiebebi im SemTxvevaSi, rodesac pacients aReniSneba cvlilebebi eleqtrokardiogramaze (gaxangrZlivebuli QRS da maRali T kbili), moicavs kalciumis glukonatis intravenur gamoyenebas – 10% Ca gluconate 0,5–1,0 ml/kg neli nakadiT 5-10 wuTis ganmavlobaSi. SeniSvna: gaiTvaliswineT bradikardia da pacienti imyofebodes monitoringze.

urgentuli RonisZiebebis sxva meTodebi aseve moicavs forsirebul diurezs hidrataciiTa da furosemidiT, xolo damatebiT SesaZloa Semdegi RonisZiebebis gamoyeneba:

- 0,9% fiziologiuri xsnari 10-20ml/kg 1 saaTis ganmavlobaSi + furosemidi 1-3mg/kg wonaze nakadurad an 15-30 wT-iani infuziiT

- salbutamoli: inhalacia 0,1 mg/kg 4-6sT-Si. intravenurad 1-2 mikrogrami/kg neli infuziiT

- glukoza 20-50%: 1gr/kg glukoza + 0,3 U insulini/kg 0.5 sT infuziiT.

- im SemTxvevaSi Tu cvlilebebia eleqtrokardiogramaze (farTe QRS da maRali T kbili), saWiroa kalciglukonatis 10% xsnaris gamoyeneba doziT 0,5 – 1 – 2 ml/kg 10-15 wuTis ganmavlobaSi. gaiTvaliswineT bradikardia da pacienti iyos eleqtrokardiogramis monitoringze.

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- Tu gamoixateba metaboluri acidozi, gamoiyeneT natriumis bikarbonati 1-2 mmoli/kg intravenurad neli nakadiT.

hiperfosfatemia

• gamovricxoT egzogenuri fosfori dietis saSualebiT. aluminis hidroqsidi an kalciumis karbonati SegviZlia gamoviyenoT oralurad 4 X dReSi doziT 0,5 – 0,15 gr/kg.

• maqsimaluri hiperhidratacia (5 000 ml/m2/24 sT-Si) forsirebiT.

• Sardis pH ar unda aRematebodes 7-s.• hipertonuli glukoza 20-50% ise, rom 1 gr/kg glukozas unda

ematebodes 0,3 erTeuli/kg regularuli insulini. am ukanasknelis infuzia grZeldeba 0,5 saaTis ganmavlobaSi.

• Tu fosforis raodenoba metia 5 mmoli/l-ze + P x Ca > 6,4 saWiroa hemodializi.

• maqsimalurad gamovricxoT Ca-is gamoyeneba, Tu es SesaZlebeli iqneba. Tumca, Tu hipokalcemia iwvevs eleqtrokardiogramis cvlilebebs mxolod maSin viyenebT Ca glukonatis 10% xsnars.

hipokalcemia da hipomagnezemia

• koregirebas moiTxovs mxolod simptomuri hipokalcemia da aseve misTvis saxasiaTo cvlilebebi eleqtrokardiogramaze. gamoiyeneba kalciglukonatis 10% xsnari doziT 0,5 – 1 – 2 ml/kg 10-15 wuTis ganmavlobaSi. gaiTvaliswineT bradikardia da pacienti iyos eleqtrokardiogramis monitoringze.

• hipomagnezeumis SemTxvevaSi gamoiyeneba MgSO4 0,2 – 0,8 mmoli/kg-ze neli nakadiT intravenurad.

oliguria / anuria

• definicia oliguria/anuria termini gamoiyeneba im SemTxvevaSi, rodesac Sardis gamoyofa < 5 ml/m2/sT-Si. aRniSnuli sindromi upiratesad uviTardebaT pacientebs antineoplaziuri mkurnalobis dawyebis dros da igi ZiriTadad grZeldeba 7-10 dRis ganmavlobaSi. mas mizezad, rogorc wesi, udevs lizisis mwvave sindromi. Tu am periodSi pacients ar Cautarda saswrafo saTanado RonisZiebebi, maSin SesaZloa sikvdili ganviTardes hiperkalemiis mizeziT. aseT konteqstSi oliguria definicirdeba Semdegnairad: Sardis gamoyofa < 5 ml/m2/sT-Si maSin, rodesac pacients miewodeba hidratacia 130 – 200 ml/m2/sT-Si intravenurad da forsirebisTvis gamoiyeneba furosemidi iseTi maRali doziT, rogoricaa 10mg/kg/dReSi.

• Tu pacients maqsimaluri hiperhidrataciis da forsirebuli diurezis fonze ar gamoexata dadebiTi dinamika, mowmdeba Semdegi

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maCveneblebi: kaliumi, fosfati, kreatinini, SardmJava da keTdeba saSarde gzebis ultrasonografia. im SemTxvevaSi, Tu:

- Ka > 7 mmoli/l an > 6 mmoli/l, magram izrdeba hiperhidrataciis da forsiurebuli diurezis miuxedavad

- P > 5 mmoli/l an Ca x P > 6,4- kreatinini 10-jer > asakobriv normaze- SardmJava > 600 mkmoli/l- Sardis gamoyofa < 50ml/m2/sT-Si maSin, rodesac hidratacia

mimdinareobs 130-200 ml/m2/sT-Si da forsireba 10mg/kg/dReSi furosemidiT

- saSarde gzebis obstruqcia orive mxares

pacients utardeba hemodializi. specifiuri dializis protokoli unda ganaxorcielos pediatrma-nefrologma da marTos pacienti zemoT aRniSnuli maCveneblebisa da klinikuri mdgomareobis gaumjobesebamde hematologTan erTad.

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hiperleikocitozi

leikocitozi xSirad Tan axlavs mwvave leikemiis prezentacias, magram igi yovelTvis ar aris dakavSirebuli garTulebebTan. termini hiperleikocitozi ZiriTadad asocirebulia im mdgomareobasTan, rodesac leikocitebis saerTo raodenoba = an > 100 000/l.

mwvave lizisis sindromi, metaboluri problemebi, Tirkmlis ukmarisoba aris dakavSirebuli hiperleikocitozTan.

hiperleikocitozis menejmenti

problema RonisZiebebimwvave lizisis sindromi - citoreduqtiuli fazis intensiobis

Semcireba: prednizoloni 0,1-0,2 mg/kg/dReSi

- mwvave lizisis sindromis prevencia da Terapia

leikostazi - intravenuri hidratacia 5% G/0.45% NaCl aa 3,000 – 5,000 ml/m2/dReSi

- intravenuri alkalinizacia: NaHCO3 100 – 200 mmoli/m2/dReSi

- alopurinoli: 300 + 100 mg/m2/dReSi oralurad an intravenurad

- davicvaT siTxis balansi - pH = 7 – 7,5 da Sardis xvedriTi wona <

1,010- ar gadaasxaT eriTrocitebi manam, sanam

ar ganviTardeba mZime anemia (Hb < 80g/l)

- SenacvlebiTi transfuzia an leikoferezi

hemoragia- Trombocitebis

raodenoba < 20,000 - koagulopaTia

- Trombocitebis transfuzia

- axlad gayinuli plazmis transfuzia

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hemoTerapia

eriTrocitebis transfuzia

leikemiiT daavadebul pacientebs, rogorc diagnozisas, aseve mkurnalobis periodSi, xSirad uviTardebaT anemia, romelic ZiriTadad meoradia da moiTxovs eriTrocitebis transfuzias.

- anemiis xarisxi ganisazRvreba Hb doniT. eWvi ar aris, rom rodesac Hb < 70 – 80g/l, pacienti saWiroebs eriTrocitebis transfuzias. rodesac Hb meryeobs 80-100g/l-mde da pacienti aris asimptomaturi, pediatrma-hematologma-onkologma Tavi unda Seikavos transfuziisagan.

- eriTrocitebis aragegmiuri saswrafo transfuziebi utardebaT im pacientebs, romlebsac aReniSnaT mwvave sisxldena.

- pacientebi, romelTac aReniSnebaT iseTi komorbiduli mdgomareobebi, rogoricaa gulis daavadebebi, cudad itanen anemias da maT xSirad uviTardebaT kardiovaskularuli gadatvirTva. aseT pacientebs transfuzia unda miewodoT dabali doziT da, Tu saWiroa, fraqcionalurad 3 – 5 ml/kg 3-4 saaTis ganmavlobaSi.

- eriTrocitebis transfuziisas misi dozireba eyrdnoba imas, rom 1ml/kg eriTrocitebis koncentratma hematokriti unda gazardos 1 %-iT da aseTi gaangariSebiT pacientebs, romlebic 20kg-mde iwonian, unda gadaesxaT 10-15 ml/kg, xolo pacientebi, romelTa wona metia 20 kg-ze, SesaZloa gadaesxaT 300 ml-mde.

- eriTrocitebi pacients unda gadaesxas ABO identuri da Rd SeTavsebadi donorisagan.

plazmis transfuzia

- SenacvlebiTi Terapiisa da leikoferezis dros- masiuri hemoragiebis dros: 20-30 ml/kg wonaze- disiminirebul sisxlZarRvTa Sida koagulopaTiis, sefsisis

drosa aseve 20-30 ml/kg wonaze- perikardiumis drenaJis Semdeg: 20-30 ml/kg wonaze

Trombocitebis transfuzia

Trombocitebis transfuziis Cvenebebi da rekomendaciebi:Trombocitebis raodenoba situaciebi< 10 yovelTvis aucilebelia< 20 - infeqcia, T > 38,5 C

- sefsisi- disiminirebuli sisxlZarRvTa Sida

koagulopaTia

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- mniSvnelovani hemoragiebi: kuW-nawlavis traqtidan urogenitaluri lorwovani retinuli

- mZime mukozitebi- meqsnikuri ventilacia- fibroskopia- Trombolizuri / antikoagulaciuri

Terapia- leikocitebi > 100 000 + sisxldenaintravenurad amfotericini B

< 30 - 40 - disiminirebuli sisxlZarRvTa Sida koagulopaTia

- lumbaluri punqcia- centraluri venis kaTeterizacia- biofsia

< 50 - 60 - hemoragia cntralur nervul sistemaSi- perikardiumis drenaJi- qirurgiuli Careva

< 100 - neiroqirurgiuli Careva

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qimioTerapiis dros mosalodneli infeqciebis profilaqtika

1. Pneumocystis carinii – iT gamowveuli pnevmoniis profilaqtikayvela pacientma, romelic imyofeba qimioTerapiis qveS, unda miiRos trimetoprimi 5mg/kg kviraSi sami momdevno dRis ganmavlobaSi.mxedvelobasi unda miviRoT metotrexatis gadasxma an oraluri miReba, am periodSi trimetoprimis miReba ar unda emTxveodes metotreqsatis dReebs.

im SemTxvevaSi Tu pacients trimetoprimze aReniSna alergiuli reaqcia kanze gamonayariT an bronqospazmiT, trimetoprimi icvleba pentamidinis izeTionatiT: 150mg/5ml dReSi.2. fungaluri infeqciis profilaqtikis mizniT yvela im pacients romelsac utardeba maRaldozirebadi qimioTerapia, oralurad eZlevaT amfotericin B suspenzia : < 3welze 100mg yovel 6 saaTSi erTxel; >3welze 200mg. alternativaa natamicini 12.5 -25 mg yovel 6 saaTSi erTxel. B 3. virusuli infeqciebis profilaqtika bolo wlebis gamokvlevebiT ar dadasturda rogorc aucilebeli,gamonaklisia is SemTxvevebi roza pacients aqvs kontaqti romelime bavSvTa infeqciebTan.4. aseve ar dadasturda granulocitebis mastimulirebeli faqtoris GG-CSF(filgastrimi) profilaqtikuri gamoyenebis efeqturoba.

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neitropeniuli cxeleba da misi marTva

definicia: neitropeniuli cxeleba definicirdeba im SemTxvevaSi, Tu pacients aReniSneba cxeleba 38,5 C erTxel an 38 C erTi saaTis ganmavlobaSi da periferiul sisxlSi neitrofilebis absolituri ricxi < 500/l.

diagnozi – ikvleva:

• sisxlis, ganavlis da Sardis baqteriologia;

• Tu SesaZlebelia, keTdeba kandidas da aspergilozis antigenebi;

• gulmkerdis rendgenografia an muclis Rrus sonografia emateba, Tu pacients aReniSneba pulmonaruli an abdominaluri simptomebi; im SemTxvevaSi, Tu rendgenologiurad filtvSi gamovlinda cvlilebebi, unda gakeTdes gulmkerdis kompiuteruli tomografia.

• C reaqtiuli cila

Terapia:

Terapia iwyeba aminoglikozidis da mesame Taobis cefalosporinis kombinaciiT. 48 saaTis Semdeg Tu pacientis ar aReniSna dadebiTi dinamika (anTebis parametrebis da klinkuri niSnebis erToblioba) antibiotikoTerapia unda gafardovdes, mesame Taobis cefalosporini icvleba imipenemiT an meronemiT.

vankomocini antibaqteriuli Terapiis nebismier safexurs emateba im SemTxvevebSi roca: mosalodnelia an dadasturebuli BBlaqtam rezistentuli stafilokoki, kaTeterTan asocirebuli infeqcia an miRebuli aqvs maRaldozirebuli citozari.

miuxedavad mimdinare antibiotikoTerapiisa, Tu cxeleba da neitropenia persistirebs me-5, me-7 dRidan, mkurnalobas emateba amfotericini B infuziebi.

antibiotikoTerapiis xangrZlivoba

Terapia ixsneba roca:- pacienti afebriluria bolo 24 saaTis ganmavlobaSi;- aqvs kargi zogadi mdgomareoba;- anTebis markerebi normaa an daqveiTebuli- neitrofilebis saerTo raodenoba > 500/l

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dabali riskis neitropeniuli epizodis (pacients ar utardeba remisiis induqcia da mosalodneli neitropeniis xangrZlivoba ar aRemateba 7 dRes da ar aReniSneba kerovani infeqciebis niSnebi) imarTeba oraluri antibiotikebis kombinaciiT:

ciprofloqsacini 20mg/kg/dRamoqsacilini 50mg/kg/dR

neotropeniis gaRrmavebis an klinikuri mdgomareobis gauaresebis SemTxvevaSi, isini gadadian maRali riskis jgufSi da ewyebaT intravenuri antibioptikoTerapia.

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dadasturebuli infeqciebis marTva

baqteriemia dadasturebuli baqteriemiis SemTxvevaSi pacients dauyovnebliv ewyeba antibiotokoTerapia sensitiurobis mixedviT. aseve xdeba inicialuri antibiotikebis modifikacia. Terapiis xangrZlivoba unda moicavdes 10 -14 dRes.

fungaluri infeqciebiinicialuri diagnostikuri RonisZiebebi emsaxureba, dadgindes infeqciis lokalizacia. Kkompiuteruli tomografia irCeva imis mixedviT, Tu ra klinikuri Civilebi aqvs pacients: otiti, sinusiti, pneomoniti, hepatiti, meningiti an encefaliti.

Tu SesaZlebelia kompiuterul kvlevas emateba aspergilozis da kandidad antigenebis gamoyofa.

fungaluri infeqciebis mkurnalobis standartul medikaments warmoadgens amfotericini. Mmisi uefeqtobis an toqsiurobis SemTxvevaSi gamoiyeneba vorikonazoli an kaspofungini. itrakonazoli SesaZloa gamoviyenoT dacviTi Terapiis saxiT.

virusuli infeqciebiZiriTadad gvxdeba martivi herpesi, herpes zosteri da citomegalovirusuli infeqciebi. maTi diagnostika emyareba antisxeulebis aRmoCenas sisxlSi da Sesabamis klinikur monacemebs. dadasturebuli martivi herpesisa da herpes zosteris infeqciebis SemTxvevaSi pacients eniSneba acikloviri, varicela zosteris SemTxvevaSi 500 mg/m2 yovel 8 saaTSi erTxel peros an intravenurad, xolo martivi herpesis SemTxvevaSi 250 mg/m2 yovel 8 saaTSi erTxel. mkurnaloba grZeldeba manam, sanam sruliad ar alagdeba kanze arsebuli gamonayari. rodesac pacients acikloviri eZleva intravenurad, pacienti saWiroebs damxmare hidrataciul Terapias Tirkmlis toqsiurobis profilaqtikis mizniT. orive SemTxvevaSi oraluri Tu intravenuri Terapiis dros kviraSi erTxel mowmdeba kreatitininis done sisxlSi.

citomegalovirusuli infeqcia klinikurad vlindeba sxvadasxva lokalizaciebiTa da Sesabamisi simptomebiT. pacinets SeiZleba aReniSnos koliti, ezofagiti, hepatiti, pnevmonia, retiniti, encefaliti. diagnozi emyareba sisxlSi citomegalovirusis antisxeulebis titris aRmoCenas, klinikur niSnebs da radiologiur kvlevebs. dadasturebis SemTxvevaSi iniSneba gancikloviri 5 mg/kg/dReSi intravenurad an oralurad. mkurnalobis xangrZlivoba minimum 14 dRea. 14 dRis Semdeg sasurvelia gadamowmdes virusis Tvisobrivi maCveneblebi PCR –iT da Sesabamisad gadawydes mkurnalobis Sewyveta an gaxangrZliveba.

81

gancikloviris xmarebisas pacienti Rebulobs adekvatur hidratacias, kreatinini da kreatininis klirensi mowmdeba yovel meore dRes.

Pneumocystis Carinii-iT gamowveuli pnevmonia

Pneumocystis Carinii aris mniSvnelovani oportunistuli infeqcia imunokompromisirebul pacientebSi. leikemiiT daavadebul pacientebSi igi SesaZloa 5-10%-Si ganviTardes da upiratesad gamoixateba mZime pnevmoniisaTvis damaxasiaTebeli klinikuri niSnebiT. diagnostikuri kriteriumebi emyareba:

• uecari respiratoruli simptomebis ganviTareba taqipnoeTi da cxelebiT

• progresirebadi respiratoruli distres sindromi cxviridan gamonadeniTa da interkostaluri SeboWilobiT Semdegomi sunTqvis ukmarisobiT.

• pacienti unda ganekuTvnebodes mZime imunokompromisirebul jgufs

• auskutaciuri monacemebi mwiria axali gulmkerdis rendgenogramaze. vlindeba bilateraluri difuzuri infiltratebi.

• naxvelSi paTologiuri organizmis demonstrireba an filtvis bioftatSi Pneumocystis Carinii–is aRmoCena.

Terapia iwyeba trimetopriniT 20/100 mg/kg/dReSi intravenurad an oralurad. mkurnalobis xangrZlivoba moicavs 21 dRes klinikuri simptomebis srul gaumjobesebamde. im SemTxvevaSi, Tu pacients aReniSneba alergiuli reaqcia trimetoprinze, alternatiulad gamoiyeneba pentamidinis izeTionati 4 mg/kg/dReSi intravenuri infuziiT 3 saaTis ganmavlobaSi. specifiuri mkurnalobis paralelurad pacients sunTqcisukmarisobis SemTxvevaSi utardeba Sesabamisi reanimaciuli RonisZiebebi.

82

qimioTerapiiT gamowveuli Rebinebisa da gulisrevis prevencia da mkurnaloba

qimioTerapiuli agentebi Rebinebasa da gulisrevas iwveven maTi pirdapiri an arapirdapiri moqmedebiT trigeruli zonis qemoreceptorebze (5-HT3) da Sesabamisad Terapia moicavs aRniSnuli receptorebis antagonist preparatebs. qimioTerapiuli agentebi dayofilia 5 jgufad imis da mixedviT Tu, rogori emetogenuri done gaaCniaT. done Rebinebis

sixSire %qimioTerapiuli agentebi da dozebi

5 > 90 Carmustine>250mg/m²Cisplatini>50mg/m²Ciclophosphamide>1500mg/m²dacrbazine;mechlorethamine;

4 60 - 90 CarboplatinCarmustine< 250mg/m²cisplatin<50mg/m²Cyclophosphamide>750mg7m-2Cytarabine>1g/m²doxorubicin>60mg/m²MTX> 1 000mg7m²procarbazin(oral)

3 30 - 60 Cyclophosphamide>750mg/m² or oralDoxorubicin in 20 to 60 mg/m²Epitubicin<90mg/m².Idarubicin,ufosfamide; MTX250 to 1000mg/m²:Mitoxantrone<15mg/m2

2 10 – 30 capecitabine;Docetaxel; Etoposide;5-Fluroracil<100mg/m²;MTX>50mg/m² to250mg/m²;Mitomicin;Paclitaxel:Topotecan,

1 <10 leomycin;busulfan;Chlorambucil(oral)2-chlorodeoxyadenosine;fludarabine;Hydroxyurea;MTX<50mg/m²; Thioguanine(oral),Vicristine;vinblastine;

• done 1 < 10 ar saWiroebs profilaqtikas

• done 2; 10-30 rutinulad gamoiyeneba deqsametazonisa da fenoTiazinis kombinacia

• done 3-4; 30-90 saWiroebs 5HT3 receptorebis antagonistebs + deqsametazoniT.

• done 5; >90 5HT3 receptorebi + deqsametazoni

83

5HT3 receptorebis antagonistebidan klinikurad uxSiresad gamoiyeneba ondasteroni (zofrani, emetroni) intravenurad 0,15 mg/kg an 5 mg/m2 samjer dReSi. sadReRamiso maqsimaluri doza sasurvelia ar aRematebodes 32 mg-s. deqsametazonis kombinaciis SemTxvevaSi pacients eZleva 4-8 mg yovel 8 saaTSi erTxel.

tkivili da misi menejmenti

tkivili simsivniT daavadebul pacientebSi SesaZloa gamowveuli iqnas mTeli rigi faqtorebiT: simsivnis masis zewoliT an infiltraciiT sxvadasxva qsovilebSi da igi cnobilia simsivnesTan asocirebuli tkiviliT. qimioTerapiasTan da radioTerapiasTan dakavSirebuli tkivili asocirebulia qsovilebis dazianebasTan, infeqciebTan, nekrozebsa da obstruqciebTan.

tkivilis samarTavad gamoiyeneba analgeziuri saSualebebi, romelic dayofilia 2 ZiriTad jgufad:

1. araopioiduri analgeziuri medikamentebi - ZiriTadad isini ganekuTvnebian arasteroidul anTebis sawinaaRmdego preparatebs da gamoiyenebian msubuqi simZimis tkivilis dros. aRniSnuli medikamentebis tipebi da dozireba ixileT Semdeg cxrilSi:

medikamentis tipi tipiuri standartuli dozebi

Acetaminophen 10 - 15 mg/kg oralurad yovel 4 saaTSi erTxel maqs. doza 650 mg

Aspirin 10 - 15 mg/kg oralurad yovel 6-8 saaTSi erTxel maqs. doza 650 mg

Ibuprofen 10 mg/kg oralurad yovel 6-8 saaTSi erTxel maqs. erTjeradi doza 800 mg

Naproxen 5-7,5 mg/kg oralurad yovel 12 saaTSi erTxel maqs. doza 500 mg

Ketorolac 0,5 - 1 mg/kg oralurad yovel 6 saaTSi erTxel maqs. erTjeradi doza 30 mg xangrZlivoba maqsilamalurad 5 dRe

2. opioidebi boWavs centralur receptorebs centralur nervul sistemaSi da periferiul qsovilebSi Semdgomi analgeziuri efeqtis miRweviT da isini gamoiyenebian saSualo da Zlieri tkivilebis dros.

84

opioidebis dozebi da tipebi

medikamenti oraluri sawyisi dozireba

medikamentis formebi

intravenuri sawyisi dozireba

Codeine 0,5 – 1 mg/kg yovel 6 saaTSi erTxelmaqs. doza 60 mg

tableti 30 mg da xsnari 3 mg/ml

0,5 – 1 mg/kg yovel 6 saaTSi erTxelmaqs. doza 60 mg

Morphone 0,3 – 0,6 mg/kg yovel 12 saaTSi erTxel

ampulebi: 2mg/ml, 5mg/ml, 10mg/ml, 15mg/mltabletebi: 1tabletebi: 15mg, 30mg, 60mg, 100mg, 200mgxsnari: 2mg/ml

0,1 mg/kg 2-4 saaTSI erTxelmaqs. doza 15 mg

Fentanyl < 15 kg ukuCvenebaa> 2 welze da iwonis 15-40 kg, 5-15 mkg/kg wonazemaqs. doza 400 mkg> 40 kg: 5mkg/kg

ampulebi: 50mkg/mlkapsulebi: 100, 200, 300, 400mkg

1-2 mkg/kgmaqs. doza 50 mgfentanilis infuzia gaxangrZlivebulia: 1mkg/kg/sT

85

invaziur procedurebTan dakavSirebuli tkivili da maTi marTva

invaziuri procedurebi (Zvlis tvinis aspiracia, Zvlis tvinis biofsia endolumbaluri punqcia) yvelaze mtkivneuli da tramvuli manipulaciaa simsivniT daavadebul pacientebSi. amisaTvis, manipulaciis Catareba unda moxdes anesTeziis gamoyenebiT. anesTezia moklea da SesaZloa Catardes, rogorc intravenurad, aseve niRbis (inhalaciuri) saSualebebiT. anesTezias atarebs specialisti-anesTeziologi, romelsac gaaCnia sakmarisi gamocdileba da flobs codnas anesTeziis mosalodneli garTulebebis marTvaSi. saanesTezio oTaxi aRWurvili unda iyos saanesTezio gaidlainiT mowodebuli yvela saWiro medikamentiT, monitoriT, defibrilatoriT.

sxva ufro nakleb tramvuli manipulaciebi intravenuri, kanqveSa da intramuskularuli ineqciebi unda Catardes lokaluri anesTeziiT adgilobrivad lidokainis an lidokainis malamos anesTeziuri diskis aplikaciis gamoyenebiT.

86

parenteraluri kveba

xSirad qimioTerapiis fonze ganviTarebuli garTulebebis (mZime stomatiti, ezofagiti, gastriti, enterokoliti) gamo SeuZlebeli xdeba enteraluri kveba, ris gamoc saWiro xdeba parenteraluri kvebis dawyeba.

parenteraluri kvebis gaidlaini:

kaloriebis procentuli Semadgenloba faqtiurad iseTive unda iyos, rogorc oraluri dietis SemTxvevaSi: 30 % cximi, 50 – 60% naxSirmJavebi da 10-20 % cilebi.

cximis 30% -iani kaloria miiRweva cximovani emulsiebiT – intralipidi, lipozini 10-20%. cximis sadReRamiso raodenoba ar unda aRematebodes 4 g/kg.

naxSirwylovani kaloriebisaTvis gamoiyeneba 20-25% deqstroza.

Cilovani kaloriebisTvis gamoiyeneba 10-20%-iani aminomJaveebis krebuli gaangariSebuli sxeulis wonaze. axalSobilebsa da bavSvebSi cilis rekomendirebuli dozebia:

0-05 w --------------------- 2,2 g/kg0,5 – 1 w ------------------2 g/kg1-3 w ----------------------- 1,8g/kg4-6 w ------------------------1,5 g/kg7-10 w -----------------------1,2 g/kg11-14 w -------------------- 0,8 g/kg

sadReRamiso siTxis kaloriebis da eleqtrolitebis dozireba ixileT Semdeg cxrilSi:

asaki siTxe (ml/kg)

kaloriebi eleqtrolitebi (milieqvi/kg)

0-1 130 100-2001-8 80-120 75-909-5 50-75 60-75>15 50 45-55

yvela asakisaTvis:Sodium 2.0-4.0Potassium 1.5-2.0Calcium phosphate 0,15-0.20Magnezium 0.1-0.25

• faqtorebi, romlebic zrdis kaloriul reJims aris: cxeleba (12% TiToeul gradusze, qirurgiuli Careva (20-30%), zrdis naklovaneba 50-100%)

• faqtorebi romlebic zrdis siTxis raodenobas moicavs: cxelebas, diareas, hiperventilacias, Rebinebas da poliurias.

87

• totaluri parenteraluri kvebis dros SesaZloa ganviTardes metaboluri darRvevebi, ris gamoc saWiroa frTxili monitoringi RviZlis fermentebis, sisxlSi glukozisa da eleqtrolitebis balansis.

qimioTerapiuli sqemebis dokumentacia

88

faza 1

wona kg simaRle= sm

s/f= m2

(1 sT)

60 mg/m2/d

1.5 mg/m2/d

30 mg/m2/d

5,000 U/m2/d

maqs.: 2.0 mg/dR

mg

mg

mg

dawy. Tar. dasr. Tar.

centri:

saxeli:

dab/Tar.:

TariRi

faza 2

wona kg simaRle = sm

s/f = m2

(1 sT) 1,000mg/m2/d+ MESNA: 400 mg/m2 i/v x3 0, 4, 8 sT-ze

75 mg/m2/d

(28d) 60 mg/m2/d mg

mg

mg

mgasakobrivi doza:

(mg)w Zv/t

dRe

dozis modifikacia? citostatikuri agentebis damateba Tu amoReba? ki – aramodifikaci(eb)is da mizez(eb)is aRwera:

SeavseT damatebiTi toqsiurobis forma 1 da 2 fazebisTvis! xelmowera gaugzavneT Sevsebuli asli kvlevis nacionalur

koordinators

dRe 33: remisia?

ki

ara


protokoli I

(1sT)

c.n.s.-2, c.n.s-3 statusis, an travmuli lumbaluri punqciis SemTxvevaSi: damatebiTi MTXIT me-18/27 dReebze

Zv/t-Si > 5% blastebic.s.s-Si blastebiSuasayris simsivne >30% sawyis zomaze

89

faza 1

wona= kg simaRle= sm

s/f= m2

(1 sT)

60 mg/m2/d

1.5 mg/m2/d

30 mg/m2/d

5,000 U/m2/d

maqs.: 2.0 mg/dR

mg

mg

mg


centri:

saxeli:

dab/Tar.:

TariRi

faza 2

wona kg simaRle= sm

s/f= m2

(1 sT) 1,000mg/m2/d+ MESNA: 400 mg/m2 i.v. x3 0, 4, 8 sT-ze

75 mg/m2/d

(28d) 60 mg/m2/d mg

mg

mg

mgasakobrivi doza:

(mg)w Zv/t

dRec.n.s.-2, c.n.s-3 statusis, an travmuli lumbaluri punqciis SemTxvevaSi: damatebiTi MTXIT me-18/27 dReebze


SeavseT damatebiTi toqsiurobis forma 1 da 2 fazebisTvis! xelmowera gaugzavneT Sevsebuli asli kvlevis nacionalur

koordinators

dRe 33: remisia?

ki

ara Zv/t-Si > 5% blastebic.s.s-Si blastebiSuasayris simsivne >30% sawyis zomaze


risk jgufi:

: protokoli

(1 sT)

90

protokoli mM centri:

saxeli:

dab/Tar.:

wona

simaRle

s/f

kg

sm

m2

risk jgufi:

25 mg/m2/d

2,000 mg/m2(24 sT)

mg/d

mg

mg

xelmowera gaugzavneT Sevsebuli asli kvlevis nacionalur koordinators

TariRi

(saRamos, rZis gareSe)

(10% 0.5 sT-Si, 90% 23.5 sT-Si)

(1 sT MTXinf. dawy-dan) =

asakobrivi doza:

mg; mg; mg; mg;w:

Zv/t

dRe


SeavseT damatebiTi toqsiurobis forma TiToeuli saSualo dozis MTX-Tvis!

dacva

w: w: w:

15 mg/m2 i.v. saaTebze: 42, 48, 54

92

protokoli Mwona

simaRle=

s/f=

kg

sm

m2

5,000 mg/m2

mg/d

mg/dR

asakobrivi doza:

mg

mg; mg; mg; mg;w: w: w: w:

Z/t

dRe


xelmowera

SeavseT damatebiTi toqsiurobis forma TiToeuli maRali dozis MTX-Tvis!

gaugzavneT Sevsebuli asli kvlevis nacionalur koordinators

TariRi

centri:

saxeli:

dab/Tar.:

25 mg/m2/d(saRamos, rZis gareSe)

(10% 0.5 sT-Si, 90% 23.5 sT-Si)

(24 sT)

15 mg/m2 i.v. saaTebze: 42, 48, 54dacva

(mg)sT

sT

sT

sT

sT

gaxangrZlivebuli dacva

ki ara

sT-mde

(mg)sT

sT

sT

sT

sT

ki ara

sT-mde

(mg)sT

sT

sT

sT

sT

ki ara

sT-mde

(mg)sT

sT

sT

sT

sT

ki ara

sT-mde

CF-dacva

gaxangrZlivebuli dacva gaxangrZlivebuli dacva

CF-dacva

gaxangrZlivebuli dacva

CF-dacva CF-dacva

risk jgufi:

(1 sT MTXinf. dawy-dan)

(56 d)

93

faza 1

wona= kg simaRle= sm

s/f= m2

protokoli IITerapiis mxari: centri:

saxeli:

dab/Tar.:

(1 sT)

10 mg/m2/d

30 mg/m2/d

10,000U/m2/d

mg

mg

mg

(1sT)

(maqs.: 2.0mg/SD)

faza 2

TariRi

wona kg simaRle= sm

s/f= m2

(1 sT) 1,000mg/m2/d + MESNA: 400 mg/m2 i.v. x3 0, 4, 8 sT-ze

75 mg/m2/d

(14d) 60 mg/m2/d mg

mg

mg

mgasakob. doza:

(mg)w Zv/t

dRedadebiTi c.n.s –is SemTxvevaSi: damatebiTi MTXIT 1 da 18 dReebzedozis modifikacia? citostatikuri agentebis damateba Tu amoReba? ki – aramodifikaci(eb)is da mizez(eb)is aRwera:

SeavseT damatebiTi toqsiurobis forma 1 da 2 fazebisaTvis! xelmowera


Tavis dasxiveba:

ki

ara -dan:-mde

sruli doza:

fraqciebis #

grei

6-MP/MTX-is dawyeba:

1.5 mg/m2/d

94

faza 1

faza 2

wona kg simaRle= sm

s/f= m2

wona kgsimaRle= sm

s/f= m2

Terapiis mxari: centri:

saxeli:

dab/Tar.:

(1 sT)

10 mg/m2/d

1.5 mg/m2/d

30 mg/m2/d

mg

mg

mg

(1sT)

(maqs.: 2.0mg/dR)

TariRi

(1 sT) 500 mg/m2/d + MESNA: 200 mg/m2 i.v. x3 0, 4, 8 sT-ze

75 mg/m2/d

60 mg/m2/d mg

mg

mg

mgasakob. doza:

(mg)w

dadebiTi c.n.s –is SemTxvevaSi: damatebiTi MTXIT 1 da 18 dReebze

Zv/t

dRe


SeavseT damatebiTi toqsiurobis forma 1 da 2 fazebisaTvis!

xelmowera


6-MP/MTX-is dawyeba:

Tavis dasxiveba:

ki

ara -dan:-mde

sruli doza:

fraqciebis #

grei

10,000U/m2/d

protokoli III

95

wona

simaRle=

s/f

kg

sm

m2

Terapiis mxari: HR-1’ bloki

centri:

saxeli:

dab/Tar.:

Zv/t

dRe

TariRi

monacemebi blokis dawyebamde:

pacienti remisiaSia? ki ara

dozis modifikacia? citost. agentebis damateba Tu amoReba? ki – ara

modifikaci(eb)is da mizez(eb)is aRwera:

(mg)

ki ara

-mdexelmowera

SeavseT damatebiTi toqsiurobis forma!

sT

sT

sT

sT

sT


mgmg

mgmg

asakobrivi doza

www

w

maR/doz. MTX-is dawy-dan 1 sT

gaxangr. dacva

20 mg/m2/d

1.5 mg/m2/d

mg/d

mg(maqs.: 2.0 mg/SD)

(3sT)(x 12sT-Si)

mg

(24sT) 5,000mg/m2

mg

mg

mg

mg

15 mg/m2x3 (sT: 42, 48, 54)

(1sT) 200mg/m2 x5 (q 12sT)(+ MESNA: 70 mg/m2 i.v. x3 0, 4, 8 sT-ze)

(2sT) 25,000 U/m2/d

dacva

dacva

bloki

2,000mg/m2 x2

96

wona

simaRle

s/f

kg

sm

m2

Terapiis mxari:

bloki HR-2’bloki

centri:

saxeli:

dab/Tar.:

Zv/t

dRe

TariRi



dozis modifikacia? citost. agentebis damateba Tu amoReba? ki – aramodifikaci(eb)is da mizez(eb)is aRwera:

(mg)

ki ara

-mdexelmowera

SeavseT damatebiTi toqsiurobis forma!sT

sT

sT

sT

sT


mxolod dadebiTi c.n.s. mqone pacientebSi

mgmg

asakobrivi doza

www maR/doz. MTX-is dawy-dan 1 sT

20 mg/m2/d

3 mg/m2/d

mg/d

mg(maqs.: 5.0 mg/SD)

(24sT) 30 mg/m2 mg

(24sT)5,000 mg/m2 mg

30 mg/m2x3 (sT: 42, 48, 54)mg

(1sT) 800 mg/m2 x5 mg

(1sT) 25,000 U/m2/d(+ MESNA: 300 mg/m2 i.v. x3 0, 4, 8 sT-ze)

mg

gaxangr. dacvadacva

wmgmg

dacva

97

wona

simaRle

s/f

kg

sm

m2

Terapiis mxari:

bloki HR-3’bloki

centri:

saxeli:

dab/Tar.:

dRe

TariRi



dozis modifikacia? citost. agentebis damateba Tu amoReba? ki – aramodifikaci(eb)is da mizez(eb)is aRwera:

xelmowera


SeavseT damatebiTi toqsiurobis forma!

mgmgmgmg

asakobrivi doza

www

w

20 mg/m2/d mg/d

mg(3sT)2,000mg/m2 x4x (12sT)

(1sT) 100 mg/m2 x5x (12sT)

mg

(2sT) 25,000 U/m2/d

mg

98

dacviTi Terapia

cikli saxeli: dab/Tar: wona: kg simaRle: sm s/f: m2

TariRi

kvira

mg/kv

mg/d

eriT trans (#)

motexil (?kv)

osteonekrozi(ki/ara)

xelmowera

* sisxlis bioqimia:

mg/kg3 kumulaciuri dRe kviraSi

doza:

dRe:

mg

sisxlis bioqimia*

20 mg/m2/kv

50 mg/m2/d(dReebi: 1-70)

Tr. trans (#)

antibiot(dReebis #)

99

mwvave limfoiduri leikemiis recidivis sawinaaRmdego mkurnalobis protokoli

ALL-REZ BFM 2002

ALL-REZ BFM 2002 protokoli warmoadgens optimizirebul Terapias bavSvTa asakis mwvave limfoiduri leikemiis recidivebis SemTxvevaSi. aRniSnuli protokoliT mkurnaloba tardeba germaniisa da avstriis yvela klinikaSi da Sveicariis zogierT onko-hematologiur centrebSi. dizaini

SeniSvna: aRniSnul dizainSi ar aris naCvenebi randomizirebuli mkurnalobis 2 mxare, romelic moicavs protokol II-sa da idarubicinebs. qarTveli pacientebisaTvis SerCeulia protokolis mxolod 2 mxare.

riskis jgufebis definicia

imunofenotipi: ara T imunofenotipi: Tadgili

droizolir. eqstramed.

kombinir. Zvlis tvin

izolirebuli Zvlistvinovani

izolir. eqstramed

kombinir. Zvlis tvin

izolirebuli Zvlistvinovani

Zalian adreuli

adreuli

gviani

S2

S2

S1

S4

S2

S2

S4

S3

S2

S2

S2

S1

S4

S4

S4

S4

S4

S2

GG

R1R1 R2R2

29282726252420 23222119181716151410 131211987654321

CC F1F1 F2F2 R1R1 R2R2 R1R1 R2R2 R1R1 R2R2

D /VD /V2424

DD 1212

CC F1F1 F2F2 R1R1 R2R2

CC F1F1 F2F2 R1R1 R2R2

II SS SS SS

Rerovani ujredis gadanergvaRerovani ujredis gadanergva

Rerovani ujredis gadanergvaRerovani ujredis gadanergva

R1R1 R2R2 R1R1 R2R2

G?G?

G?G?

GG

G?G?

G?G?

G?G?

G?G?

GG GG

jgufi kvira

RR

RR

S1

S4

S3

S2

100

recidivis ganviTarebis drois definiciebi:

dro diagnozis dasmis Semdeg Terapiis damTavrebis Semdeg

gviani

adreuli

Zalian adreuli

> 18 Tve da

< 18 Tve da

> 6 Tve

< 6 Tve

< 6 Tve

Terapiuli gegma S1 jgufis pacientebisaTvis

citoreduqtiuli prefaza, romelic mimdinareobs deqsametazonis gamoyenebiT, grZeldeba induqciis 2 blokiT: F1 da F 2. Semdgomi Terapia grZeldeba 6 R1 da R2 blokebis monacvleobiT. aRniSnuli jgufis pacientebSi dacviTi Terapia moicavs 12 Tves.

Terapiuli gegma S2 jgufis pacientebisaTvis

citoreduqtiuli prefaza, romelic mimdinareobs deqsametazonis gamoyenebiT, grZeldeba induqciis 2 blokiT: F1 da F 2. Semdgomi Terapia grZeldeba 8 R1 da R2 blokebis monacvleobiT. aRniSnuli jgufis pacientebSi dacviTi Terapia moicavs 24 Tves.

Terapiuli gegma S3 da S4 jgufis pacientebisaTvis

citoreduqtiuli prefaza, romelic mimdinareobs deqsametazonis gamoyenebiT, grZeldeba induqciis 2 blokiT: F1 da F 2. Semdgomi Terapia grZeldeba 3 R1 da R2 blokebis monacvleobiT da myari remisiis miRebis SemTxvevaSi pacients utardeba Rerovani ujredis gadanergva.

101

Terapiuli elementebi

citoreduqtiurli prefaza citoreduqtiuli prefazis daniSnulebas warmoadgens miRweul iqnas kargad kontrolirebadi reduqcia inicialuri leikemiuri ujredebis masisa. pacientebi Rebuloben deqsametazons doziT 6mg/m2 5 dRis ganmavlobaSi. citoreduqtiuli fazis mimdinareobisas yuradsaRebia simsivnis mwvave lizisis sindromis ganviTareba, ris gamoc pacients utardeba yvela prevenciuli RonisZieba. (ix. mwvave lizisis sindromi)

citoreduqtiuli prefazis dawyebisas yvela pacients ukeTdeba endolumbaluri punqcia 3 qimiuri preparatis kombinaciiT. xolo is pacientebi, romelTac aReniSnebaT centraluri nervuli sistemis dazianeba, ganmeorebiT intralumbalur punqcias Rebuloben me-6 dRes.

medikamentebis dozireba da maTi intralumbalurad gamoyenebis wesebi ixileT mwvave limfoiduri leikemiis samkurnalo protokolSi.

qimioTerapiuli blokebis sqemebi

bloki F1

medikamenti miRebis forma doza dReebi

DEXA p.o. 20 mg/m2/dR 1 2 3 4 5

VCR i.v. 1.5mg/m2/dR 1 6

MTX infuzia 36 sT 1mg/m2 1 4

ASP infuzia 6 sT 10 000 U/m2

MTX lumbalurad asakobrivi 1

ARA-C lumbalurad asakobrivi 1

PRED lumbalurad asakobrivi 1

bloki F2


DEXA p.o. 20 mg/m2/dR 1 2 3 4 5

VCR i.v. 1.5mg/m2/dR 1

ARA-C infuzia 3 sT 2 X 3mg/m2/dR 1 2

ASP infuzia 6 sT 10 000 U/m2 4




102

bloki R2


DEXA p.o. 20 mg/m2/dR 1 2 3 4 5

6-TG p.o. 100 mg/m2/dR 1 2 3 4 5

VDS i.v. 3 mg/m2/dR 1

MTX infuzia 36 sT 1 g/m2 1

IFO infuzia 1 sT 400 mg/m2/dR 1 2 3 4 5

DNR infuzia 24 sT 35 mg/m2/dR 5

ASP infuzia 6 sT 10,000 U/m2 6




SeniSvna: centraluri nervuli sistemis dazianebis SemTxvevaSi lumbaluri punqcia gaimeoreT me-5 dResac.

bloki R1


DEXA p.o. 20 mg/m2/dR 1 2 3 4 5

6-MP p.o. 100 mg/m2/dR 1 2 3 4 5

VCR i.v. 1.5 mg/m2/dR 1 6

MTX infuzia 36 sT 1 g/m2 1

ARA-C infuzia 3 sT 2 X 2g/m2 5

ASP infuzia 6 sT 10.000 U/m2 6




SeniSvna: TiToeuli qimioTerapiuli blokis mimdinareobisas pacients esaWiroeba Tanmxlebi infuzuri Terapia, romelic identuria maRali riskis blokuri Terapiis infuzuri Terapiisa (ix. maRali riskis blokebis Terapiuli sqemebi); metotreqsatis Tanmxlebi Terapia ixileT metotreqsatis gadasxmis Terapiul gegmaSi.

103

recidivis lokalizaciis definiciebi

1. izolirebuli Zvlis tvinis recidivi – Tu Zvlis tvini Seicavs > 25% limfoblastebs da eqstramedularuli leikemiis niSnebi ar aris gamoxatuli.

2. kombinirebuli Zvlistvinovani recidivi – Zvlis tvini Seicavs > 5 % limfoblastebs da gamoxatulia Tundac erTi adgilis eqstramedularuli manifestacia.

3. cns recidivi – cerebrospinaluri siTxe Seicavs >5/mikro l birTvian ujredebs. cns recidivi SesaZloa gamoixatos simsivnuri masis ganviTarebiT cerebrospinalur siTxeSi blasturi ujredebis ararsebobisas. kompiuteruli an magnetur-rezonansuli tomografiiT aRmoCenili simsivnuri masa Seswavlili unda iqnas histologiurad.

4. testikularuli recidivi – adgili aqvs calmxrivi an orive mxris saTesle parkebis gadidebas da mtkivneulobas. maTSi limfoblastebis infiltracia unda dadasturdes biofsiiT.

104

ALL IC-BFM 2002 - მედპორტალი · blasturi ujredebis imunologia - mll leikemiis...

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Transcript of ALL IC-BFM 2002 - მედპორტალი · blasturi ujredebis imunologia - mll leikemiis...