arahojkinis limfomis multicentruli Terapiuli oqmi bavSvTa ...arahojkinis limfomis multicentruli Terapiuli oqmi bavSvTa asakSi B-NHL BFM 2004 - 1 - oqmis sinofsi ... imunologia histologia,

arahojkinis limfomis multicentruli Terapiuli oqmi

bavSvTa asakSi

B-NHL BFM 2004

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oqmis sinofsi

1. protokoli gaixsna 2004 wlis ianvarSi2. protokolis dizaini: multidisciplinirebuli

ararandomizirebuli qimioTerapia3. protokolis mkurnalobis Cvenebebi: dadasturebuli arahojkinis

limfoma an mwife B ujredovani mwvave limfoiduri leukemia4. asaki: 0-18 weli5. stratifikacia: standartuli Terapiis jgufs ganekuTvnebian R1-dan

R4-mde riskis jgufis pacientebi. specialur Terapias moiTxoven Semdegi pacientebi:

• pacientebi inicialuri centraluri nervuli sistemis (cns) dazianebiT

• pacientebi pirveladi mediastinaluri arahojkinis limfomiT6. radomizireba aRniSnul oqmSi ar aris gaTvaliswinebuli.

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protokolis dizaini

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standartuli Terapiuli gegma

modificirebuli Terapiuli gegma pirveladi mediastinaluri arahojkinis limfomebisTvis

B-NHL BFM 2004

l.d.h. < 500 erTMTX 1 gr/m2

l.d.h. > 500 erTMTX 5 gr/m2

modificirebuli Terapiuli gegma cns inicialuri dazianebis SemTxvevaSi

lumbaluri punqcia 3 medik. reparatiT

inicialuri diagnostikuri masalis miReba da kvleva

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koncefcia I

Zvlis tvinis, plevris an ascituri siTxe

punqcia

imunologiuri da citomorfologiuri kvleva

mxolod simsivne

biofsia

koncefcia II

histologiuri da imunohistoqimiuri kvleva

imunologia histologia, imunohistoqomia

citomorfologia citogenetika

inicialuri stadirebisTvis saWiro kvlevebi

• dawvrilebiTi anamnezi da fizikaluri gasinjva• gul-mkerdis rendgenografia or proeqciaSi; pozitiuri

pasuxis SemTxvevaSi keTdeba gulmkerdis kompiuteruli tomografia

• muclis Rrus sonografia; pozitiurobis SemTxvevaSi muclis Rrus kompiuteruli tomografia an magnitur-rezonansuli tomografia

• Zvlis tvinis punqcia erTi wertilidan; gamonakliss warmoadgenen pacientebi III stadiiT da l.d.h. > 500 erT-ze, maTTan Zvlis tvinis punqcia tardeba ori wertilidan

• lumbaluri punqcia

• plevris an asceturi siTxis citomorfologia

• imunologiuri da citogenetikuri kvlevebi pozitiuri Zvlis tvinis plevris an asceturi siTxis

• Tavis tvinis magnitur-rezonansuli an kompiuteruli tomografia mxolod im SemTxvevaSi, Tu pacients aReniSneba cns dazianebis klinikuri niSnebi

• ConCxis Zvlebis rendgenografia mxolod im SemTxvevaSi, roca pacients aReniSneba Zvlebis tkivili

• sisxlis saerTo analizi • sruli bioqoimiuri analizi

• eleqtrolituri balansis SeswavlisaTvis sruli analizi

• laqtatdehidrogenazas (l.d.h.) Seswavla

• eleqtrokardiografia

• eqokardiografia

• yvela sxva damatebiTi kvlevebi individualuria da saWiro xdeba gansakuTrebuli klinikuri niSnebis gamovlenis SemTxevvaSi

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organoebis dazianebis definiciebi

• Zvlis tvinis dazianeba definicirdeba im SemTxvevaSi, rodesac Zvlis tvinis nacxebSi gamoyofilia > 5% limfoblastebi.

• cns dazianeba definicirdeba, Tu cerebrospinaluri siTxidan gamoiyofa limfoblastebi; pacients radiologiurad gamouvlindeba intracerebraluri simsivnuri warmonaqmni; pacients aReniSneba klinikurad gamoxatuli cns dazianebis niSnebi, romelsac sxva eqstracerebraluri mizezi ar gaaCnia.

• saTesle parkebis dazianeba saTesle parkebis dazianeba pirveladad diagnostirdeba klinikuri niSnebi mixedviT: mtkivneuloba, SeSupeba. am SemTxvevaSi pacienti ar saWirobs pirvelad orxiqtomias da biofsias. damatebiT tardeba saTesle parkebis ultrasonografiuli kvleva.

• Zvlebis dazianeba definicirdeba im SemTxvevaSi, Tu pacients aReniSneba rendgenologiuri niSnebi Zvlebis dazianebis. Tu Zvlebis dazianeba warmoadgens mxolod erTaderT niSans daavadebis ganviTarebisa, aucileblad tardeba biofsia Semdgomi histologiuri kvleviT.

• filtvebis dazianebadefinicirdeba mxolod gul-mkerdis kompiuteruli tomografiiT da aseve, Tu igi mxolod erTaderT niSans warmoadgens daavadebis gamovlenis, saWiro biofsia Semdgomi histologiiT.

• mediastinaluri dazianeba aseve definicirdeba mxolod kompiuteruli tomografiis monacemebiT. diagnozisas Tu pacients sxva periferiuli limfuri kvanZebis an organoebis dazianeba ar aReniSneba, saWiroa biofsiuri masalis miReba Suasayaridan Torakotomiis saSualebiT. gamonaklis SemTxvevas warmoadgenen pacientebi, romelTac Zalze didi Suasayaris simsivnis gamo aReniSnebaT sunTqvis an gulsisxlZarRvTa sistemis ukmarisobis niSnebi. maT diagnostikuri Torakotomia utardebaT mxolod mdgomareobis dastabilurebis Semdeg (eniSnebaT hormonoTerapia 0,5mg/kg wonaze 3-5 dRis ganmavlobaSi simsivnis dapataravebis mizniT).

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arahojkinis limfomebis stadireba

stadia I • dazianebulia erTi nodaluri an eqstranodaluri adgili

• mediastinaluri da abdominaluri lokalizaciebi, Tundac erTi lokalizaciiT, ar miekuTvnebian pirvel stadias.

stadia II • ramodenime nodaluri an eqstranodaluri dazianeba diafragmis erT mxares

• mediastinaluri epiduraluri lokalizaciebiT meore stadias ar miekuTvnebian.

stadia III • diafragmis orive mxares lokalizacia• yvela Torakaluri manifestaciebi

(mediastinumi, Tinusi, plevra).• epiduraluri da multilokaluri

Zvlebis dazianeba.stadia IV • Zvlis tvinis an cns dazianeba

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mwife B ujredovani leikemiis definicireba

SemTxveva unda akmayofilebdes Semdeg kriteriumebs:

• Zvlis tvinis aspiratSi blastebis raodenoba > 25%• blastebi morfologiurad ganekuTvnebian L3 morfologias• imunologiurad blasturi ujredebis > 20% unda uCvenebdes

mwife B ujredis markerebs (membranuli imunoglobulinebi kappa an lambda).

• blastur ujredebSi aRmoCenil unda iqnes qromosomuli translokaciebi t(8; 14), t(8; 22) an t(2; 8).

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Terapiuli jgufebis definicireba

Terapiuli jgufebis definicireba xorcieldeba stadiis inicaluri l.d.h-s donis da inicaluri operaciis Sedegebis mixedviT.

Terapiuli jgufi

rezeqcia stadia + l.d.h

R1 sruli

R2 arasruli stadia I + IIstadia III da l.d.h. < 500

R3 arasruli stadia III da l.d.h. 500-dan, magram <1000stadia IV/B-ALL da l.d.h. <1000 da cns negatiuria

R4 arasruli stadia III da l.d.h. > 1000stadia IV/B-ALL da l.d.h. > 1000 an cns pozitiuria

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qimioTerapiuli gegma

cxrili 1:

cxrili 2:

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standartuli Terapia B-NHL da B-ALL-Tvis

cxrili 3:

Terapiuli elementebi

1. citoreduqciuli prefaza V

citoreduqtiuli faza ar utardebaT mxolod R1 jgufis pacientebs. yvela sxva pacients qimioTerapia ewyebaT citoreduqtiuli faziT.

citoreduqtiuli fazes dawyebis kriteriumebi:

• pacients ar aReniSneba mZime infeqcia

• pacients ar aReniSneba operaciis Semdgomi sicocxlisaTvis SeuTavsebeli garTulebebi

• diurezi normaluria- pacients Catarebuli aqvs mwvave lizisis sindromis

profilaqtika - pacients ar aReniSneba oligoanuria

dReebi 1 2 3 4 5deqsametazoni ○ ○ ○ ○ ○ ○ ● ● ● ● ● ● ● ● ●ciklofosfamidi ● ●lumbaluri punqcia ●

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pirveladi mediastinaluri B-NHL-Tvis

l.d.h. < 500 erTMTX 1 gr/m2

l.d.h. > 500 erTMTX 5 gr/m2

lumbaluri punqcia 3 medik.

MTX/ARA-C/PRED

deqsametazoni: 5mg/m2/dR oralurad an intravenurad gayofili 3 dozaze. dRe 1 - 2.

10mg/m2/dR oralurad an intravenurad gayofili 3 dozaze. dRe 3, 4, 5.

ciklifosfamidi: 200mg/m2/dR 1 saaTiani infuziiT. dRe 1 – 2.

ciklofosfamidis paralelurad mimdinareobs hidratacia 3000ml/m2/dR diurezis balansis dacviT. cistitis profilaqtikis mizniT intravenurad keTdeba mesna 70mg/m2

ciklofosfamidis dawyebidan 0, 4, 8, sT-ze.

lumbaluri punqcia metotreqsatiT, citozariT da prednizoloniT:keTdeba 1 dRes da dozebi asakobrivia.

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

pacientebs inicialuri centraluri nervuli sistemis dazianebis SemTxvevaSi lumbaluri punqcia sami preparatiT utardebaT pirvel da mesame dRes.

radgan pacientebi NHL -iT da B-ALL-iT warmoadgenen maRal risks simsivnuri ujredebis zalian swrafi daSlisas, LLcitoreduqtiuli prefazis Catarebisas didi yuradReba eqceva lizisis mwvave sindromis profilaqtikasa da mkurnalobas.

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

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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:

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.

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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

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

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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 50–6610 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:

- 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.

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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.

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

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- 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.

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.

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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.

- 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

- 18 -

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 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.

- 19 -

kursi A4

dReebi 1 2 3 4 5

deqsametazoni ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●vinkristini ●citozari ●● ●●etopozidi ● ●metotreqsati ●leikovorini

ifosfamidi ● ● ● ● ●lumbaluri metotreqsati, citozari, prednizoloni

●

deqsametazoni: 10mg/m2/dR oralurad an intravenurad gayofili sam micemaze. dRe 1 – 5.

- 20 -

422

48 54

vinkristini: 1,5mg/m2 intravenurad, maqsimaluri doza 2 mg., neli nakadiT 1 saaTiT adre metotreqsatis dawyebamde.

citozari: 150mg/m2 1 saaTis ganmavlobaSi, yovel 12 saaTSi erTxel. dRe me-4 da me-5. citozari ismxeba vepizidis micemamde.

azidi: 100mg/m2/dR 2 saaTis ganmavlobaSi 24 saaTSi erTxel. dRe me-4 da me-5. medikamenti ixsneba fiziologiur xsnarSi ganzavebiT 1:50. etopozidi pacients eZleva citozaris Semdeg.

gafrTxileba: arteriuli wnevis daqveiTeba, alergiuli reaqciebi, ariTmia, ris gamoc pacienti imyofeba eqimis dakvirvebis qveS medikamentis gadasxmisas da momdevno 5 saaTis Semdeg.

metotreqsati: 1gr/m2 4 saaTis ganmavlobaSi sinjis gareSe. Sardis alkalinizacia mimdinareobs 48-e saaTamde. 42, 48 da 54 saTebze keTdeba gegmiuri leikovorinebi.

ifosfamidi: 800 mg/m2 1 saaTis ganmavlobaSi. dRe 1 – 5. parareluri hidrataciiT 3000ml/m2/dR diurezis balansis dacviT. cistitis profilaqtikis mizniT keTdeba mesna 300mg/m2

0, 4 da 8 saaTze ifosfamidis dawyebidan.

lumbaluri punqcia: keTdeba me-2 dRes sami preparatiT: metotreqsati, citozari da prednizoloni. Semdegi asakobrivi dozebiT:

asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 21 -

kursi A24 mxolod pirveladi mediastinaluri B-NHL pacientebisaTvis

dReebi 1 2 3 4 5



●


- 22 -

422

48 54



etopozidi: 100mg/m2/dR 2 saaTis ganmavlobaSi 24 saaTSi erTxel. dRe me-4 da me-5. medikamenti ixsneba fiziologiur xsnarSi ganzavebiT 1:50. etopozidi pacients eZleva citozaris Semdeg.

gafrTxileba: arteriuli wnevis daqveiTeba, alergiuli reaqciebi, ariTmia, ris gamoc pacienti imyofeba eqimis dakvirvebis qveS medikamentis gadasxmisas da momdevno 5 saTis Semdeg.

metotreqsati: 1gr/m2 24 saaTis ganmavlobaSi. dozis 1/10 30 wT-is ganmavlobaSi, 9/10 – 23 1/2-sT-is ganmavlobaSi. Sardis alkalinizacia mimdinareobs 48-e saaTamde. 42, 48 da 54 saTebze keTdeba gegmiuri leikovorinebi.




asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 23 -

kursi AA24

dReebi 1 2 3 4 5



●


- 24 -

422

48 54









asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 25 -

kursi AAZ1 inicialuri centraluri nervuli sistemis mqone pacientebisaTvis

dReebi 1 2 3 4 5 6

deqsametazoni ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●vinkristini ●citozari ●● ●●etopozidi ● ●metotreqsati ●leikovorini


●● ●


- 26 -

422

48 54








lumbaluri punqcia: keTdeba me-2, me-4 da me-6 dRes sami preparatiT: metotreqsati, citozari da prednizoloni. Semdegi asakobrivi dozebiT:

asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 27 -

kursi AAZ2 inicialuri centraluri nervuli sistemis mqone pacientebisaTvis

dReebi 1 2 3 4 5 6

deqsametazoni ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●vinkristini ●citozari ●● ●●etopozidi ● ●metotreqsati ●leikovorini


●●



- 28 -

422

48 54







lumbaluri punqcia: keTdeba me-2 da me-6 dRes sami preparatiT: metotreqsati, citozari da prednizoloni. Semdegi asakobrivi dozebiT:

asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 29 -

kursi B4

dReebi 1 2 3 4 5

deqsametazoni ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●vinkristini ●doqsorubicini ● ●metotreqsati ●leikovorini

ciklofosfamidi ● ● ● ● ●lumbaluri metotreqsati, citozari, prednizoloni

●


vinkristini: 1,5mg/m2 intravenurad, maqsimaluri doza 2 mg., neli nakadiT 1 saaTiT adre metotreqsatis dawyebamde. vinkristini ar keTdeba R1 jgufis pacientebSi!

- 30 -

422

48 54

doqsorubicini: 25mg/m2/dR 1 saaTis ganmavlobaSi. me- da me-5 dRes.

gafrTxileba: doqsorubicinis gadasxmamde unda Catardes eqokardiografia da eleqtrokardiografia. mniSvnelovani darRvevebis aRmoCenis SemTxvevaSi xdeba dozis reducireba an misi Sewyveta.

metotreqsati: 1gr/m2 4 saaTis ganmavlobaSi sinjis gareSe. Sardis alkalinizacia mimdinareobs 48-e saaTamde. 42, 48 da 54 saTebze keTdeba gegmiuri leikovorinebi.

ciklofosfamidi: 200mg/m2 1 saaTis ganmavlobaSi. dRe 1 – 5. paraleluri hidrataciiT 3000ml/m2/dR diurezis balansis dacviT. cistitis profilaqtikis mizniT keTdeba mesna 70mg/m2 0, 4 da 8 saaTze ifosfamidis dawyebidan.


asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 31 -

kursi B24 mxolod pirveladi mediastinaluri B-NHL pacientebisaTvis

dReebi 1 2 3 4 5



●


vinkristini: 1,5mg/m2 intravenurad, maqsimaluri doza 2 mg., neli nakadiT 1 saaTiT adre metotreqsatis

- 32 -

422

48 54

dawyebamde. vinkristini ar keTdeba R1 jgufis pacientebSi!



metotreqsati: 1gr/m2 24 saaTis ganmavlobaSi. dRe 1. dozis 1/10 30 wT-is ganmavlobaSi, 9/10 – 23 1/2-sT-is ganmavlobaSi. Sardis alkalinizacia mimdinareobs 48-e saaTamde. 42, 48 da 54 saaTebze keTdeba gegmiuri leikovorinebi.



asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 33 -

kursi BB 24

dReebi 1 2 3 4 5



●



- 34 -

422

48 54






asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 35 -

kursi BBZ1 pirveladi centraluri nervuli sistemis dazianebis mqone pacientebisaTvis

dReebi 1 2 3 4 5 6

deqsametazoni ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●●vinkristini ●doqsorubicini ● ●metotreqsati ●leikovorini


●●

●



- 36 -

422

48 54





lumbaluri punqcia: keTdeba me-2, me-4 da me-6 dRes sami preparatiT: metotreqsati, citozari da prednizoloni. Semdegi asakobrivi dozebiT:

asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 37 -

kursi BBZ2 pirveladi centraluri nervuli sistemis dazianebis mqone pacientebisaTvis

dReebi 1 2 3 4 5 6

deqsametazoni ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●●vinkristini ●doqsorubicini ● ●metotreqsati ●leikovorini


● ●



- 38 -

422

48 54





lumbaluri punqcia: keTdeba me-2 da me-6 dRes sami preparatiT: metotreqsati, citozari da prednizoloni. Semdegi asakobrivi dozebiT:

asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 39 -

kursi CC

dRe 1 2 3 4 5deqsametazoni ●●● ●●● ●●● ●●● ●●●vindezini ●citozari ●● ●●etopozidi ●● ●● ●lumbaluri metotreqsati, citozari, prednizoloni

●


vindezini: 3mg/m2 maqsimaluri doza 5 mg., neli nakadiT 1 saaTiT adre citozaris dawyebamde.

citozari: 3gr/m2 erTjeradi doziT. infuzia 3 saaTis ganmavlobaSi. dRe 1 da 2. sumarulad pacients eZleva 4 maRaldozirebuli citozari 12 saaTSi erTxel. maRaldozirebuli citozaris infuziamde 0,5 sT-iT adre pacients ukeTdeba vitamini

- 40 -

B6 150mg/m2; yovel 8 saaTSi erTxel eniSneba deqsametazonis Tvalis wveTebi.

gafrTxileba: ataqsiis da, nistagmis gamovlenisas citozaris infuzia wydeba.

Etopozidi: 100mg/m2 2 saaTis ganmavlobaSi. 3-5 dRe. Yovel 12 saaTSi erTxel. sumarulad pacienti Rebulobs 5 infuzias. pirveli infuzia iwyeba me-3 dRis dilas. medikamenti zavdeba fiziologiur xsnarSi 1:50 ganzavebiT.

gafrTxileba: arteriuli wnevis daqveiTeba, alergiuli reaqciebi, ariTmia, ris gamoc pacienti imyofeba eqimis dakvirvebis qveS medikamentis gadasxmisas da momdevno 5 saaTis Semdeg.


asakiwlebi

MTX(mg)

ARA – C(mg)

PRED(mg)


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

- 41 -

metotreqsatis gadasxmis oqmi 1000mg/m2 da 5000mg/m2/24sT

E HdRe 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

- 42 -

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)

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)

- 43 -

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)

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

- 44 -

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.

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.

SeniSvna: metotreqsati 1gr/m2 4 saaTis ganmavlobaSi – metotreqsatis done sisxlSi isazRvreba 4, 24, 36 (+ anu mxolod im SemTxvevaSi, rodesac 24 saaTianma donem uCvena maRali maCvenebeli) 42, 48 saaTze. am SemTxvevaSic metotreqsatis cudi eliminaciis marTva zustad iseTivea, rogorc zemoT aRniSnul 24 saaTiani infuziebis dros.

- 45 -

damxmare Terapia

damxmare Terapia, romelic moicavs infeqciebis profilaqtikas, neitropeniul cxelebas, dadasturebuli infeqciebis marTvas, Rebinebisa da tkivilis menejments, identuria mwvave limfoiduri leikemiis damxmare Terapiisa. ixileT mwvave limfoiduri leikemiis samkurnalo protokoli.

- 46 -

literatura:

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- 49 -

arahojkinis limfomis multicentruli Terapiuli oqmi bavSvTa ...arahojkinis limfomis multicentruli Terapiuli oqmi bavSvTa asakSi B-NHL BFM 2004 - 1 - oqmis sinofsi ... imunologia histologia,

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