bavSvTa asakis mwvave mieloiduri leikemiis samkurnalo protokoli · 2015. 1. 23. · mieloiduri an...

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bavSvTa asakis mwvavemieloiduri leikemiissamkurnalo protokoli

AML – BFM 2004

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mwvave mieloiduri leikemia

Sesavali

mwvave mieloiduri leikemia defincirdeba rogorc Rerovani ujredis simsivnuri transformaciiT gamowveuli klonaruli darRveva. diferencirebisa da apoptozis normaluri riTmis darRvevis fonze Zvlis tvinsa da eqstramedularul organoebSi adgili aqvs simsivnuri mieloiduri ujredebis akumulacias.mwvave mieloidur leikemiad iwodeba mdgomareoba, rodesac Zvlis tvini Seicavs 20%-ze met leikemiur blastebs. klonaluri daavadebas safuZvlad udevs mravlobiTi mutaciebi da qromosomuli cvlilebebi multipotentur Rerovan ujredSi.

epidemiologia

bavSvTa asakis leikemiebis 20% warmoadgens. Tanabari gadanawileba fiqsirdeba mdedrobiT da mamrobiT sqesSi. saqarTveloSi wlis ganmavlobaSi daaxloebiT fiqsirdeba 8-10-12 SemTxveva.

etiologia

mwvave mieloiduri leikemiis gamomwvevi mizezi zustad ar aris dadgenili, xelSemwyob faqtorebad miCneulia ekologiuri faqtorebi – maRali radiaciuli foni, garemos navTobis produqtebid dabinZureba; nayofis Casaxvis periodSi mSoblebis mier alkoholis da narkotikuli nivTierebebis gamoyeneba; mozardebSi marixuanas moweva;

mwvave mieloiduri leikemiis ganviTrebis mniSvnelovan faqtors warmoadgens genetikuri riski. Ddadgenilia misi ganviTarebis maRali albaToba identur tyupebSi; aseve gamoyofilia mTeli rigi qromosomuli sindromebi, romlebic asocirebulia mieloiduri leikemiis ganviTarebis maRal riskTan. Aam mimarTulebiT gamoyofen Tandayolil da SeZenil genetikur sindromebs:

Tandayolili sindromebia:

daunis sindromi; ojaxuri monosomi 7 sindromi; fankonis anemia; blumis sindromi; neorofibromatozi; noonansis sindromi: kostmanis sindromi; daimond- blekfanis anemia; dandayolili amegakariocituli Trombocotopenia:

SeZenili sindromebia:

mZime aplastiuri anemia; Ramis paroqsizmuli hemoglobinuria; amegakariocituli Trombocotopenia; SeZenili monosomi 7.

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mwvave mieloiduri leikemiis klasifikacia

mwvave mieloiduri leikemiis klasifikacia eyrdnoba FAB (French-American-British) klasifikacias da ZiriTadad masSi gamoyenebulia blasturi ujredebis morfologiuri daxasiaTeba, Tumca emateba blasturi ujredebis citoqimiuri da imunologiuri maxasiaTeblebi.

• M0 – mwvave mieloiduri leikemia minimaluri diferencirebiT

am SemTxvevaSi Zvlis tvini umetesad ujredovania da Seicavs blasturi ujredebis 90%, romlebsac ar aReniSnebaT citoplazmuri granulacia, birTvakebi an aueris Cxirebi. MPO (mieloperoqsidaza) maTSi uaryofiTia. imunofenotipirebiT SesaZloa gamovlindes mieloiduri an monocituri antigenebi: CD13, CD14, CD33 an CD34, zogierTma M0 blastebma SesaZloa uCvenon TDT, romelic asocirebuli mwvave limfoidur leikemasTan.

• M1 – mwvave mieloiduri leikemia momwifebis gareSe

Zvlis tvinis aspirati avlens maRalujredovnebas upiratesad mieloblastebis siWarbiT. blastebis umetesoba iRebeba mieloperoqsidaziT. morfologiurad isini Seicaven mwir moruxo-mocisfro citoplazmas ramodenime araazurofiluri granulebiT an aueris CxirebiT. gamdinare citometriT vlindeba HLA-DR, CD13, CD33 da CD34-is eqspresia.

• M2 – mwvave mieloiduri leikemia momwifebiT

Zvlis tvini uCvenebs blasturi ujredebis garkveulwilad momwifebas. mieloblastebi warmodgebian 30%-ze meti raodenobiT. Blasturi ujredebi uxSiresad Seicaven granulebis grovebs, ris gamoc mieloperoqsidaza maTSi yovelTvis dadebiTia. M2 variantis SemTxvevaSi aueris Cxirebi da birTvakebi Zalian xSiria. imunofenotipirebiT blastebi aCveneben HLA-DR, CD13, CD33, CD11 da CD15-is eqspresias.

• M3 – mwvave promielocituri leikemia

ganasxvaveben 2 tips, romelTa Soris ufro xSirad gvxvdeba hipergranularuli varianti, romlis drosac 30%-ze meti blastebis aris promielocitebi da mieloblastebi. promielocitebis didi raodenoba Seicavs uxv granulacias, aueris Cxirebs. ufro iSviaTi mikrogranularuli variantis dros citoplazmis granulacia ufro nazia da SesaZloa ver moxdes maTi aRmoCena sinaTlis mikroskopiT. irive SemTxvevaSi blasturi ujredebi myarad avlenen mieloperoqsidazaze dadebiTobas.

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blasturi ujredebi avlenen CD13, CD33, CD11 da CD15-is eqspresias, magram uaryofiTi arian HLA-DR-ze da CD14-ze.

• M4 – mwvave mielomonocituri leikemia

M4 definicirdeba maSin, rodesac adgili aqvs, rogorc granulocituri, ise monocituri blasturi ujredebis arsebobas. blasturi ujredebi pleomorfuli arian zomiT, citoplazmis raodenobiT, granulaciiT da birTvakebiT. SesaZloa zogjer aueris Cxirebis naxva. blasturi ujredebis garkveuli nawili pozitiuria mieloperoqsidazaze, xolo darCenili nawili neirospecifiur enolazaze (NSE). mcire nawili pacientebisa M4Mvarianti SemTxvevaSi uCveneben eozinofilias Zvlis tvinSi da aRniSnuli forma definicirdeba, rogorc mielomonocituri leukemia eozinofiliiT.

blasturi ujredebi uCveneben CD13, CD15, CD33, CD14, CD11c, CD64 da HLA-DR antigenebis eqspresias.

• M5 – mwvave monocituri leikemia

araeriTroiduli ujredebis 80% warmodgenilia monocitebiT. arCeven 2 variants: M5a (aradiferencirebuli) da M5b (diferencirebuli). pacientebi M5a-s dros avlenen 80% monoblastebs, arian ufro dabali asakis da aReniSnebaT maRali leikocitozi da cudi prognozi. M5b-s dros 80%-ze meti monocituri ujredebi warmodgenilia, rogorc monocitebiT, aseve promonocitebiT da periferiul sisxlSi Warbobs mwife monocitebi. orive tipis SemTxvevaSi blasturi ujredebi avlenen mkveTr dadebiTobas NSE-ze.

imunologiurad blasturi ujredebi avlenen CD13, CD15, CD33–is eqspresias.

• M6 – mwvave eriTrocituli leikemia

bavSvebSi Zalian iSviaTia. igi definicirdeba maSin, rodesac Zvlis tvinSi aReniSneba 50%-ze meti eriTroblastebi. imunologiurad uCveneben pozitiurobas glikoforin A (GlykoA) mimarT.

• M7 – mwvave megakarioblasturi leikemia

Zvlis tvinSi Warbobs pleomorfuli megakarioblastebi, romlebic morfologiurad Znelad sadiferenciacioa, radgan xSirad emsgavsebian limfoblastebs. megakarioblastebi uaryofiTia mieloperoqsidaze da avlenen aqtiurobas PAS reaqciaze. aRniSnuli variantis diagnosis dadgenisas gadamwyveti mniSvneloba eniWeba blastur ujredebSi IIb/IIIa antigenebis aRmoCenas.

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blastebis diferencireba histoqimiuri SeRebvia mixedviT

saRebavi M0 M1/M3 M4 M5 M6 M7 ALL

Mmieloperoqsidaza- + + - - - -

Aaraspecifiuri esTeraza

Qqloracetati- + + ± - - -

Aalfa naftol acetati- - + + - ± -

sudanis Savi- + + - - - -

glikogeni - - ± ± + - +

blastebis diferencireba imunologiuri markerebis mixedviT

antigenebi M0 M1 M2 M3 M4 M5a M5b M6 M7MPO +/- +/- + + + -/+ -/+ - -

CD7 -/+ -/+ - - - + - - -

CD11c - - - - +/- +/- + - -

CD15 - -/+ + +/- + + + - -

CD20 - - - - - - - - -

CD33 + + + + + + + -/+ -/+

CD34 + + +/- - -/+ -/+ -/+ - -

CD61 - - - - - - - - +

Cd68 - - - + +/- + + - -

TdT -/+ -/+ -/+ - - - - -/+ -

GlikoA - - - - - - - + -

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mwvave mieloiduri leikemiis qromosomuli analizi

blasturi ujredebis qromosomuli analizi unda Catardes yvela SemTxvevebSi, radgan isini warmoadgenen mniSvnelovan diagnostikur da progzoul faqtors. klonaluri qromosomuli darRvevebi aRmoCenialia bavSvTa asakis Mmwvave mieloiduri leikemiebis 75% -Si.

specifiuri citogenetikuri da molekuluri darvevebi moicavs:

• AML t (8; 21) translokaciiT: asocirebulia M2 qvetipTan da granulocitur sarkomasTan. pacientebi am tranclokaciiT gamoirCevian ufro kargi gamosavliT, vidre romelime sxva qvetipi mieloduri leikemiebisa.

• AML inv (16) – iT: me-16 qromosomis inversia asocirebuli translokaciaa MM4Eo qvetipTan da aseve warmoadgens karg prognosul faqtors, rogorc bavSvebSi, ise mozrdilebSi.

• AML t (15; 17) translokaciiT: dakavSirebulia mwvave promielocitur leikemiasTan, gansazRvravs mis metad gansxvavebul paTogenezs da mkurnalobis specifiurobas. Tumca M3 variantis dros iSviaTad gvxvdeba translokacia (11;17). maTi identifikacia mniSvnelovania maTi atras mimarT dabali sensitiurobis gamo.

• AML 11q23 iT: gvxvdeba M4 da M5 formebis dros da ZiriTdad axasiaTebT arakeTilsaimedo prognozi.

• AML t(1;22) : gamoyofilia mwvave megakarioblasturi leikemiis dros. igi uxSiresad gvxdeba adreul asakSi da iSviaTd daunis sindromTan ganvuTarebul M7 formebSi. translokacia xasaiTdeba cudi prognoziT.

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mwvave mieloiuduri leikemiis prognozuli faqtorebi.

• asaki: ar warmoadgens prognizul faqtors im pediatriul pacientebSi, romlebsac mkurnaloba utardebaT multiagenturi intensiuri qimioTerapiiT.

• rasa :kavkasiuri rasis warmomadgenlebs aqvT ufro kargi gamosavali, vidre afrikul-amerikuls.

• leikemiuri ujredis maxasiaTeblebi: moicavs leikocitebis inicialur raodenobas, Bmorfologiur klasifikacias, citogenetikur da molekulur darRvevebs (ix zemoT).

• pasuxi Terapiaze: kargi da naadrevi pasuxi qimioTerapiaze dakavSirebulia karg prognozTan.

daavadebisGgamosavali da gadarCenis sixSire

miuxedavad Tanamedrove qimioTerapiuli reJimebis danergvisa da Tanmxlebi Terapiis daxvewisa, uSemTxvevo gadarCenis sixSire mwvave mieloidur leikemiiT davadebul bavSvebSi ar aRemateba 50- 60%s.

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mwvave mieloiduri leikemiis diagnozi

rutinuli procedurebi:

1. sisxlis saerTo analizi2. Zvlis tvinis aspiratis gamokvleva:

- blasturi ujredebis citomorfologia da citoqimia- blasturi ujredebis citogenetikuri kvleva- blasturi ujredebis molekulur-genetikuri kvleva- blasturi ujredebis imunofenotipireba

mwvave mieloiduri leikemiis eqstramedularuli daavadebis gavrcelebisa da identificirebis mizniT gamoiyeneba Semdegi diagnostikuri gaidlaini:

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

saTesle parkebis (biWebSi) palpacia;3. lumbaluri punqcia;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 adgilobriv da centralur koordinatorebTan diskusiis Semdeg.

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mkurnalobaAML-BFM 2004 multicentruli optimizirebuli mkurnalobis protokoli bavSvTa asakis mwvave mieloiduri leikemiebisaTvis.

aRniSnuli protokoliT mkurnaloba utardebaT germaniis, avstriis da Sveicariis klinikebSi myof pacientebs mwvave mieloiduri leikemiis diagnoziT, romelTa asaki moicavs 0 – 18 wels.

protokolis gaxsnis TariRi - 01.03.2004damTavrebis TariRi - 28.02.2014.

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protokolis dizaini

AML-BFM 2004induqcia 1 induqcia 2 konsolidacia intensifikacia

▼ ▼ ▼ ▼ ▼ ▼ ▼dRe 1 15 21-28 42-56 88 ~112 ~140

randomizireba stratificirebaA: ARA-C citozari HAE: maRaldozirebuli citozari / etopozidiDx: liposomaluri daunorubicini; L-DNR SR: standartuli riskis jgufiI: idarubicini HR: maRali riskis jgufiE: etopozidi * im pcientebSi hyavT HLA identuri da-Zma2CDA: 2 – qloro-2-dezoqsiadenoziniHA: maRaldozirebuli citozariM: mitoqsantroniha: saSualo dozis citozari

ADxE1

R1

AIE1

SR

HR

S

Al1

HAM

haM1

Al/2-CDA

Al

R2

HAE

haM HAE

R3

12 grei 1

18 grei 1

intralumbalurad citozari;dacviTi Terapia 1 wlis ganmavlobaSi

Rerovani ujredis gadanergva*R1

S

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riskis jgufebis stratifikacia

riskis jgufebi

standartuli riski

AML FAB M3t (15;17)AML in daunis sindromian pacientebSi

maRali riski

AML FAB M0AML FAB M1/2aueris Cxirebis gareSeAML FAB M4AML FAB M5AML FAB M6AML FAB M7

AML FAB M1/2 aueris CxirebiT

AML FAB M4 eoAML t (8; 21)AML inv (16)

> 5% blastebi me-15 dRes (1 induqciis Semdeg) gadayvanil unda iqnas maRal riskSi

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citoreduqtiuli prefaza

citoreduqtiuli prefazis dros gansakuTrebuli mniSvneloba eniWeba inicialuri leikocitebis raodenobas da, Tu is naklebia 50 000/mkl-ze, pacients eniSneba remisiis induqciis kursi. im SemTxvevaSi, Tu leikocitebis sawyisi raodenoba metia 50 000/mkl-ze an gamoxatulia mniSvnelovani organomegalia, iniSneba specifiuri prefaza 6-TioguaniniT (40mg/m2/dR oralurad) da citozari (40mg/m2/dR intravenurad). alternatiulad SesaZloa hidroqsiureas gamoyeneba. aRniSnuli mkurnaloba mimarTulia blasturi ujredebis TandaTanobiT da neli ganadgurebisken. im SemTxvevaSi, Tu 3 dRis Semdeg blasturi ujredebis reduqcia ar SeiniSneba, pacients saswrafod ewyeba induqciuri Terapia. hiperleikocitozis SemTxvevaSi pacients eniSneba alopurinoli an rasburikaze Sesabamisi hidrataciis fonze. es ukanaskneli mimdinareobs fiziologiuri 0,9% da glukozis 5% xsnarebis gamoyenebiT 1:1, 3 000ml/m2

raodenobiT. hiperleikocitozis SemTxvevaSi pacients inicialuri diagnostikuri lumbaluri punqcia ar ukeTdeba. igi tardeba mas Semdeg, rac pacientTan miiRweva blastebis reduqcia.

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remisiis induqcia

AML-BFM 2004-is mixedviT remisiis induqcia tardeba 2 randomizirebuli qimioTerapiuli blokiT: ADxE1 da AIE1.

induqciuri qimioTerapia ADxE1

dizaini

citozari 100mg/m2/dR infuzia 48 sT-s ganmavlobaSi 1 dRis dilidan me-3 dRis dilamde

citozari 100mg/m2 yovel 12 saaTSi erTxel intravenurad, infuzia 30 wT-is gamvalobaSi, me-3 dRis dilidan me-8 dRis saRamomde (12 gadasxma)

liposomaruli daunorubicini 80mg/m2/dR intravenurad me-3, me-5, me-7 dReebze

citozaris infuziamde

etopozidi 150mg/m2/dR me-6, me-7, me-8 dRes 60 wT-is ganmavlobaSi. misi infuzia iwyeba 6 saaTiT adre citozaris infuziamde (anu me-8, me-10 da me-12 citozaris miRebamde). infuziis xangrZlivoba 60 wT.

citozari intralumbalurad 1 dRes an me-8 dRes im pacientebSi, romelTac inicialuri hiperleikocitozis gamo lumbaluri punqcia ar gaukeTda. dozebi asakobrivia: <1 w – 20mg; 1–2w – 26mg; 2-3w – 34mg; >3w – 40mg. im SemTxvevaSi, Tu Trombocitebis raodenoba naklebia 30 000-ze,

dRe

l.p.

Zvt.p.

ARA-C: 100mg/m2/dR. dReE1, 2.48 saaTiani infuzia

ARA-C: 100mg/m2. dRe 3 – 8. 12sT-Si x infuzia 30 wT

L-DNR: 80mg/m2/dR. dRe 3, 5, 7. infuzia 120 wT

Etopozid: 150mg/m2/dR. dRe 6, 7, 8. infuzia 60 wT.

ARA-C: lumbalurad. dRe 1 da 8.

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intralumbaluri punqciis win pacienti saWiroebs Trombocitebis gadasxmas.

Terapiaze pasuxis gansazRvra tardeba me-15 dRes da, Tu blastebis raodenoba < 5%, Terapia grZeldeba 28-e dRes, xolo rodesac > 5%, me-16 dRidan iwyeba axali Terapiuli bloki. sayuradReboa, rom pacients ar aReniSnebodes mZime infeqciebi an neitropeniuli cxeleba.

remisiis induqciis ADxE1–is paralelurad sruldeba Semdegi Terapia:

- hidratacia 3000ml/m2/dR. dRe 1-8

hidratacia sruldeba NaCl 0,9% + Glucosae 5% + NaHCO3 20mmoli yovel 500ml-ze.

- alopurinoli - balansirebuli diurezi laziqsis gamoyenebiT (1-2mg/kg/dR)- eleqtrolituri balansis kontroli yoveldRiurad da Sesabamisi

koregireba - Rebinebis sawinaaRmdego Terapia 5HT3 receptorebis antagonistebi

+ deqsametazoni

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induqciuri Terapia AIE

randomizirebis me-2 mxars induqciur TerapiaSi warmoadgens AIE.

dizaini

citozari 100 mg/m2/dR. 48 saaTiani gaxangrZlivebuli infuzia. 1 dRis dilidan me-3 dRis dilamde.

citozari 100mg/m2 yovel 12 saaTSi – 12x 30 wuTis ganmavlobaSi. me-3 dRis dilidan me-8 dRis saRamomde.

etopozidi 150mg/m2/dR. dRe 6-8. 24 sT-Si erTxel. Misi infuzia iwyeba 6 saaTiT adre citozaris infuziamde (me-8, me-10, me-12 citozaris gadasxmebamde). infuzia 60 wT-is ganmavlobaSi.

idarubicini 12mg/m2. dRe 3, 5, 7 citozaris gadasxmamde. infuzia 4 sT

citozari intralumbalurad 1 dRes an me-8 dRes im pacientebSi, romelTac inicialuri hiperleikocitozis gamo lumbaluri punqcia ar gaukeTda. dozebi asakobrivia: <1 w – 20mg; 1–2w – 26mg; 2-3w – 34mg; >3w – 40mg. im SemTxvevaSi, Tu Trombocitebis raodenoba naklebia 30 000-ze, intralumbaluri punqciis win pacienti saWiroebs Trombocitebis gadasxmas.

Terapiaze pasuxis gansazRvra tardeba me-15 dRes da, Tu blastebis raodenoba < 5%, Terapia grZeldeba 28-e dRes, xolo rodesac > 5%, me-16

dRe

l.p.

Zvt.p.

ARA-C: 100mg/m2/dR. dRE1, 2.48 saaTiani infuzia


IDR: 12mg/m2/dR. dRe 3, 5, 7. infuzia 4 sT

Etopozid: 150mg/m2/dR. dRe 6, 7, 8. infuzia 60 wT.ARA-C: lumbalurad. dRe 1 da 8.

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dRidan iwyeba axali Terapiuli bloki. sayuradReboa, rom pacients ar aReniSnebodes mZime infeqciebi an neitropeniuli cxeleba.

remisiis induqciis ADxE1–is paralelurad sruldeba Semdegi Terapia:

- hidratacia 3000ml/m2/dR. dRe 1-8

hidratacia sruldeba NaCl 0,9% + Glucosae 5% + NaHCO3 20mmoli yovel 500ml-ze.

- alopurinoli - balansirebuli diurezi laziqsis gamoyenebiT (1-2mg/kg/dR)- eleqtrolituri balansis kontroli yoveldRiurad da Sesabamisi

koregireba - Rebinebis sawinaaRmdego Terapia 5HT3 receptorebis antagonistebi

+ deqsametazoni

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induqciuri Terapia HAM mxolod maRali riskis pacientebisaTvis

standartuli riskis pacientebi HAM Terapias ar Rebuloben, xolo maRali riskis pacientebi remisiis induqciis I kursis Semdeg hematopoezis ganaxlebisasRebuloben meore remisiis induqcias HAM TerapiiT. maT Soris, im pacientebs, visac hqondaT kargi Terapiuli pasuxi me-15 dRes, HAM-is dawyebis win leikocitebis raodenoba unda hqondeT > 1000/ml. xolo pacientebs, romelTac me-15 dRes blastebis raodenoba rCebaT 5%-ze meti, HAM Terapia ewyebaT dauyovnebliv. aRniSnul pacientebSi Rrma neitropeniis dros sasurvelia granulocitebis transfuzia.

dizaini

citozari 3gr/m2. yovel 12 sT-Si erTxel. 1 dRidan me-3 dRemde. infuziis xangrZlivoba 3 sT. citozaris infuziisas pacients utardeba Tvalis sanacia deqsametazonis Tvalis wveTebiT yovel 6 saaTSi erTxel. Citozaris infuziamde 0,5 saaTiT adre intravenurad keTdeba vitamini B6 doziT 150 mg/m2. maRaldozirebuli citozaris dozebi ganicdis reducirebas asakebis mixedviT: >24 Tve – 100%; 20-24 Tve – 90%; 17-19 Tve – 80%; 14-16 Tve – 70%; 11-13 Tve – 60%; 8-10 Tve – 50%; 6-7 Tve – 40%; 4-5 Tve – 30%; <3 Tve – 20%. maRaldozirebuli citozaris gadasxmisas pacients rutinulad utardeba eleqtroencefalografia, eqokardiografia, ofTalmologis konsultacia. gadasxmisas pacienti saWiroebs sasicocxlo funqciebis monitorings da eqimis meTvalyureobas aranakleb 6 saaTisa. im SemTxvevaSi, Tu gamoixata mxedvelobis gaoreba an krunCxva, infuzia unda Sewydes da pacients unda

ARA-C: 3gr/m2. dRe 1-3. 12 sT-Si x. infuzia 3 sT.

Mitox: 10mg/m2/dR. dRe 3, 4. infuzia 30 wT.

ARA-C: lumbalurad. dRe 1l.p.

Zvt.p.

dRe

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davakvirdeT 1 saaTis ganmavlobaSi. Tu aRniSnuli simptomebi ukuganviTarda, infuzia grZeldeba. Tu pacients infuziis gagrZelebis Semdeg zemoT aRniSnuli simptomebi kvlav ganumeorda, citozaris infuzia ixsneba da misi gameoreba SeuZlebelia. maRaldozirebuli citozaris infuziisTvis gamoyenebuli unda iyos ampulebi 500 an 1000mg formebiT.

Tanmxlebi infuzuri Terapiis saxiT pacients intravenurad unda gadaesxas 2500ml/m2 siTxe fiziologiuri xsnarisa da glukozis monacvleobiT. siTxis raodenoba SesaZloa Semcirdes an gaizardos pacientis klinikuri mdgomareobis mixedviT.

Sardis disbalansis SemTxvevaSi gamoiyeneba laziqsi 0,5-1mg/kg/dR. yoveldRiurad mowmdeba eleqtrolituri balansi da xdeba Sesabamisi koregireba.

yvela pacienti Rebulobs 5HT3 receptorebis antagonists + deqsametazonTan.

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konsolidacia AI/2CDA mxolod maRali riskis pacientebisaTvis

- Terapia iwyeba HAM-is damTavrebidan 4 kviris Semdeg- pacients aReniSneba kargi klinikuri mdgomareoba da ar aqvs

infeqciebi- periferiul sisxlSi granulocitebi > 1000/mkl, Trombocitebi >

80 000/mkl.

dizaini

citozari 500 mg/m2/dR. infuzia grZeldeba 4 dRis ganmavlobaSi.

2-qloro-2-dezoqsiadenozini 6mg/m2. dRe 1, 3. infuzia 30 wT-is ganmavlobaSi.

idarubicini 7mg/m2. 60 wT-iani infuziiT. dRe 3, 5.

citozari intralumbalurad. dRe 1, 6. citozaris dozireba xdeba asakobrivad.



ARA-C: 500mg/m2/dR. dRe 1-4. 96 sT-iani uwyveti infuzia

2DCA: 6mg/m2. dRe 1, 3. infuzia 30 wT.

IDR: 7mg/m2/dR. dRe 3, 5. infuzia 60 wT.

l.p.

Zvt.p.

dRe

- 20 -


- 21 -

konsolidacia AI

- Terapia iwyeba induqciidan 4 kviris Semdeg.- pacients aReniSneba kargi klinikuri mdgomareoba da ar aqvs


80 000/mkl.

dizaini

citozari 500 mg/m2/dR. infuzia grZeldeba 4 dRis ganmavlobaSi.

idarubicini 7mg/m2. 60 wT-iani infuziiT. dRe 3, 5.

citozari intralumbalurad. dRe 1, 6. citozaris dozireba xdeba asakobrivad.




ARA-C: 500mg/m2/dR. dRe 1-4. 96 sT-iani uwyveti infuzia.

IDR: 7mg/m2/dR. dRe 3, 5. infuzia 60 wT.

ARA-C: lumbalurad. dRe 1, 6.

l.p.

Zvt.p.

dRe

- 22 -

konsolidacia hAM

- Terapia iwyeba AI/AI/2-CDA 4 kviris Semdeg.- pacients aReniSneba kargi klinikuri mdgomareoba da ar aqvs


80 000/mkl.

dizaini

citozari 1gr/m2. yovel 12 saaTSi erTxel. dRe 1-3. infuzia 3 sT-is ganmavlobaSi. citozaris infuziisas pacients utardeba Tvalis sanacia deqsametazonis Tvalis wveTebiT yovel 6 saaTSi erTxel. Citozaris infuziamde 0,5 saaTiT adre intravenurad keTdeba vitamini B6 doziT 150 mg/m2. maRaldozirebuli citozaris dozebi ganicdis reducirebas asakebis mixedviT: >24 Tve – 100%; 20-24 Tve – 90%; 17-19 Tve – 80%; 14-16 Tve – 70%; 11-13 Tve – 60%; 8-10 Tve – 50%; 6-7 Tve – 40%; 4-5 Tve – 30%; <3 Tve – 20%. maRaldozirebuli citozaris gadasxmisas pacients rutinulad utardeba eleqtroencefalografia, eqokardiografia, ofTalmologis konsultacia. gadasxmisas pacienti saWiroebs sasicocxlo funqciebis monitorings da eqimis meTvalyureobas aranakleb 6 saaTisa. im SemTxvevaSi, Tu gamoixata mxedvelobis gaoreba an krunCxva, infuzia unda Sewydes da pacients unda davakvirdeT 1 saaTis ganmavlobaSi. Tu aRniSnuli simptomebi ukuganviTarda, infuzia grZeldeba. Tu pacients infuziis gagrZelebis Semdeg zemoT aRniSnuli simptomebi kvlav ganumeorda, citozaris infuzia ixsneba da misi gameoreba SeuZlebelia. maRaldozirebuli citozaris

HD ARA-C: 1gr/m2. dRe 1-3. 12 x. 3 sT-iani infuzia

Mitoxantron: 10mg/m2/dR. dRe 3, 4. infuzia 30 wT.

ARA-C: lumbalurad. dRe 1, 6. l.p.

Zvt.p.

dRe

- 23 -

infuziisTvis gamoyenebuli unda iyos ampulebi 500 an 1000mg formebiT.

mitoqsantroni 10mg/m2/dR. dRe 3-4. infuzia 30 wT-is ganmavlobaSi.

citozari intralumbalurad. dRe 1, 6. citozaris dozireba xdeba asakobrivad




- 24 -

intensifikacia HAE

yvela pacienti intensifikacias Rebulobs HAE TerapiiT. gamonakliss warmoadgenen pacientebi, romelTac utardeba alogenuri Rerovani ujredebis gadanergva.

- Terapia iwyeba 2-4 kviris Semdeg hAM-is Semdeg.- pacients aReniSneba kargi klinikuri mdgomareoba da ar aqvs


80 000/mkl.

dizaini

citozari 3gr/m2. yovel 12 sT-Si erTxel. 1 dRidan me-3 dRemde. infuziis xangrZlivoba 3 sT. citozaris infuziisas pacients utardeba Tvalis sanacia deqsametazonis Tvalis wveTebiT yovel 6 saaTSi erTxel. Citozaris infuziamde 0,5 saaTiT adre intravenurad keTdeba vitamini B6 doziT 150 mg/m2. maRaldozirebuli citozaris dozebi ganicdis reducirebas asakebis mixedviT: >24 Tve – 100%; 20-24 Tve – 90%; 17-19 Tve – 80%; 14-16 Tve – 70%; 11-13 Tve – 60%; 8-10 Tve – 50%; 6-7 Tve – 40%; 4-5 Tve – 30%; <3 Tve – 20%. maRaldozirebuli citozaris gadasxmisas pacients rutinulad utardeba eleqtroencefalografia, eqokardiografia, ofTalmologis konsultacia. gadasxmisas pacienti saWiroebs sasicocxlo funqciebis monitorings da eqimis meTvalyureobas aranakleb 6 saaTisa. im SemTxvevaSi, Tu gamoixata mxedvelobis gaoreba an krunCxva, infuzia unda Sewydes da pacients unda

HD ARA-C: 3gr/m2. dRe 1-3. 12 x. 3 saaTiani infuzia

Etopozid: 125mg/m2/dR. dRe 2, 3, 4, 5. infuzia 60 wT.

ARA-C: lumbalurad. dRe 1. l.p.

Zvt.p.

dRe

- 25 -

davakvirdeT 1 saaTis ganmavlobaSi. Tu aRniSnuli simptomebi ukuganviTarda, infuzia grZeldeba. Tu pacients infuziis gagrZelebis Semdeg zemoT aRniSnuli simptomebi kvlav ganumeorda, citozaris infuzia ixsneba da misi gameoreba SeuZlebelia. maRaldozirebuli citozaris infuziisTvis gamoyenebuli unda iyos ampulebi 500 an 1000mg formebiT.

etopozidi 125mg/m2/dR. infuzia 1 sT-is ganmavlobaSi. dRe 2, 3, 4, 5. citozaris infuziamde 6 saaTiT adre (daiwye me-3 citozaris gadasxmamde!).

citozari intralumbalurad. dRe 1. citozaris dozireba xdeba asakobrivad.




- 26 -

centraluri nervuli sistemis Terapia

centraluri nervuli sistemis Terapiisas, rogorc citostatiuri agenti, gamoiyeneba citozari. Sruli Terapiis mimdinareobisas pacienti intralumbalur punqcias Rebulobs 12-jer. gamonakliss warmoadgenen pacientebi daunis sindromiT, romlebic dacviT Terapiaze intralumbalur Terapias ar Rebuloben.

1. inicialuri lumbaluri punqcia – pacientebs utardebaT diagnozis dasmisas, 1 dRes an me-8 dRes.

2. HAM blokSi - pirveli dRe3. blokebSi AI an AI/2CDA - 1, me-6 dRes da blokSi hAM - 1 da me-6

dRes. 4. blokSi HAE pirvel dRes.5. sxivuri Terapiisas an misi damTavrebis Semdeg 1, me-8, me-15 da 22-e

dRes.

centraluri nervuli sistemis profilaqtikuri dasxiveba moicavs 2 randomizirebul mxars da pirveli mxris Tanaxmad pacientebi sxivdebian 12 greiT, xolo meore mxris Tanaxmad - 18 greiT. pacientebi, romelTa asaki 11/4–dan 2 wlamdea, Terapias Rebuloben 12 an 15 greiT.

pacientebi, romlebic ar sxivdebian (asaki < 15 Tve), damatebiT Rebuloben intralumbalur citozars 4 kviraSi erTxel.

pacientebi, romlebsac aReniSnebaT cns dazianeba da maTi asakia 11/4–dan 2 wlamde, sxivur Terapias Rebuloben 15 greiT. danarCeni yvela pacienti, romelTa asaki > 2 welze da aReniSnebaT inicialuri cns dazianeba, sxivur Terapias Rebuloben 18 greiT. gamonakliss warmoadgenen pacientebi, romelTac utardebaT Rerovani ujredebis gadanergva.

citostatiuri Terapia intralumbaluri citozariT inicialurad dazianebuli cns-is mqone pacientebSi tardeba yovelkvireulad manam, sanam cerebrospinaluri siTxe blastebisagan ar iqneba Tavisufali.

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;

- 27 -

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

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

- 28 -

dacviTi Terapia

dacviTi Terapia iwyeba intensifikaciis damTavrebidan 4 kviris Semdeg cns-is dasxivebis paralelurad. igi grZeldeba 1 wlis ganmavlobaSi.

dizaini

Tioguanini 40mg/m2/dR yoveldRiurad saRamos Wamidan 2 saaTis Semdeg.

citozari 40mg/m2 kanqveS. yovel 4 kviraSi erTxel 4 dRis ganmavlobaSi.

citozari lumbalurad x 4 (kviraSi erTxel). daiwyeT sxivuri Terapiis paralelurad. citozaris dozebi irCeva asakobrivad.

dacviTi Terapiis aRniSnuli sqema icvleba daunis sindromian pacientebSi, isini ar Rebuloben intralumbalur Terapias. pacientebi, romelTac aqvT promielocituri leikemia, dacviT Terapiaze Rebuloben atras. ixileT Terapiuli sqema M3.

dacviTi Terapiis kriteriumebi:

TG:leikocitebi >3 000/mkl 150% dozis

>2 000/mkl 100% dozis>1 000-2 000/mkl 50% dozis<1 000/mkl 0% dozis

ARA-C:leikocitebi >2 000/mkl daTrombocitebi >80 000/mkl

TG: 40mg/m2. p.o.

ARA-C: 40mg/m2. kanqveS. 4 dRis ganmavlobaSi yovel 4 kviraSi erTxel.

ARA-C: intralumbalurad. pirveli 4 kviris ganmavlobaSi – kviraSi erTxel

dRe

1 weli

- 29 -

aRniSnuli kriteriumebis ararsebobisas erTi kviriT wydeba TioguaniniT Terapia.

- 30 -

Rerovani ujredis gadanergva AML-BFM 2004 protokolis mixedviT

qarTveli pacientebisaTvis Rerovani ujredebis gadanergvis Cvenebebi yovelTvis ar xdeba protokolis mixedviT da igi SeTanxmebulia kvlevis centralur koordinatorTan, Cvens SemTxvevaSi damatebiT ucxoel eqspertebTan (prof. nimaieri, fraiburgi, germania da prof. kingstoni, londoni, didi britaneTi).

- 31 -

mwvave promielocituri leikemia – AML FAB M3

pacientebs promielocituri leikemiiT AML-BFM 2004-is mixedviT utardebaT gansxvavebuli Terapia:

• pacientebi Rebuloben atras

• pacientebi ar Rebuloben HAM TerapiasA

• G-CSF atrasTan erTad ar gamoiyenebaM

dizaini ixileT qvemoT:

- 32 -

randomizireba HAE: maRaldozirebuli citozari/etopozidiA: ARA-C citozariDx: liposomaluri daunorubicini; L-DNRI: idarubiciniE: etopozidiHA: maRaldozirebuli citozariM: mitoqsantroniha: saSualo dozis citozari

R

induqcia 1 konsolidacia intensifikacia

12 grei18 grei

dacviTi Terapia 1 weli;lumbaluri citozari

dRe -2/-1 14 dRe dRe 18-31 dRe 38-51

HAE-s paralelurad

14 dRe yovel 3 TveSi 14 dRe

Zvt

dRe -3 dRe 1

- 33 -

- 34 -

RonisZiebebi qimioTerapiis dawyebamde

diagnozis dasmisTanave pacients eZleva atra 25mg/m2/dR oralurad gayofili 2 dozaze.

qimioTerapiis dawyeba

iwyeba remisiis induqciiT AIE/ADExE da, Tu inicialuri leikocitebis raodenoba 5000/mkl-ze dabalia, atra iwyeba me-4 dRes. Tu inicialuri leikocitebis raodenoba 5000/mkl-ze metia, qimioTerapia iwyeba atrasTan erTad.

- 35 -

AML BFM 2004FAB M3

atra 25 mg/m 2 /dR oralurad, 2 miRebaze

dRe -3/-1 14 dRemde(qimioTerapiamde 3 dRiT adre) = mg/d toqsiuroba dawyeba dasruleba dRe 18 – 31(ADxE/AIE-s dawyebidan me-18 dRes)= mg/d toqsiuroba dawyeba dasruleba dRe 38 – 51(AdxE/AIE-s dawyebidan 38-e dRes) = mg/d toqsiuroba dawyeba dasruleba

HAE-s paralelurad 14 dRe = mg/d toqsiuroba (HAE-sTan erTad dawyeba) dawyeba dasruleba

3 Tve dacviTi Terapia 14 dRe = mg/d toqsiuroba dawyeba dasruleba



- 36 -

atras gverdiTi movlenebi

- Tavis tkivili (Tavis tvinis fsevdotumori), - piris simSrale, - eriTema, - daRliloba, - arTralgiebi, - hipertriglicedemia.

retinis mJavis sindromi (atras sindromi)

- cxeleba,- pulmonaluri infiltracia,- plevris da perikardiumis simptomatika.

aRniSnuli simptomebis gamovlenisas pacients eniSneba deqsametazoni 0,5 – 2mg/kg mdgomareobis dastabilirebamde. pacientis mZime klinikuri mdgomareobis dros atras miReba SesaZlebelia droebiT Sewydes.

- 37 -

Terapia daunis sindromis mqone pacientebisaTvisdizaini

randomizirebaA: ARA-C, citozari HAE: maRaldozirebuli citozari / etopozidiDx: liposomaluri daunorubicini; L-DNR M: mitoqsantroniI: idarubicini E: etopozidi

induqcia 1

AML daunis sindromis dros

citozaris dozis reducireba

asaki/TveebSi

%/m2

Zvt

dRe

konsolidacia intensifikacia

dacviTi Terapia 1 weli

- 38 -

ha: saSualo dozis citozari

- 39 -

daunis sindromiT daavadebuli pacientebisaTvis, rogorc sqemis dizainidan sCans, miRebulia ramodenime gansxvaveba:

- induqciis TerapiaSi antraciklinebis doza Semcirebulia- pacientebis daunis sindromiT ar Rebuloben HAM blokur Terapias- konsolidaciur AI blokSi idarubicini reducirebulia 5mg/m2-mde

iseve, rogorc mitoqsantromi hAM blokSi 7mg/m2-mde- pacientebi daunis sindromiT Rebuloben mxolod 7 intralumbalur

punqcias- ar utardebaT centraluri nervuli sistemis dasxiveba

daunis sindromis mqone pacientebis mkurnalobisas gansakuTrebuli mniSvneloba eniWeba infeqciebis, mZime mukozitebis da kardiotoqsiurobis droul Sefasebas, aRmoCenas da adeqvatur mkurnalobas. Pacientebs, romlebsac gamouvlindaT aseTi garTulebebi, Semdgomi qimioTerapiuli bloki ewyebaT mas Semdeg, rac ganviTardeba hemopoezis kargi regeneracia. zemoT aRniSnuli garTulebebis gamo SesaZloa dadges sakiTxi qimioTerapiuli preparatebis dozis reducirebisa.

tranzitoruli mieloproliferaciuli sindromi

axalSobilebs daunis sindromiT, SesaZloa, gamouvlindeT tranzitoruli mieloproliferaciuli sindromi. aRniSnuli sindromi vlindeba, rogorc periferiul sisxlSi, aseve Zvlis tvinSi blastebis tranzitoruli matebiT. im SemTxvevaSi, rodesac axalSobils ar aReniSneba klinikuri simptomebi, mas Terapia ar utardeba da, rogorc wesi, yvela aseT pacients aReniSneba spontanuri gaumjobeseba. klinikuri simptomatikis gamovlenisas, SesaZloa, daeniSnos citozari doziT 0,5 – 1mg/kg 4 dRis ganmavlobaSi. aseTi axalSobilebi warmoadgenen gansakuTrebiT maRal risks imisa, rom 1-4 wlis asakSi ganuviTardeT mwvave mieloiduri leikimia.

mielosarkoma

sinonimebi:

- granulocitaruli sarkoma- qloroma- eqstramedularuli leikemia

mielosarkoma aseve saWiroebs protokoliT gaTvaliswinebul mkurnalobas. mielosarkoma warmoadgens mwvave mieloiduri leikemiis lokalur formas, ZiriTadad warmodgenilia M5 an M4 morfologiis blastebiT, mielosarkomasTan yvelaze xSirad asocirebulia translokacia t(8; 21). diagnozis dasmisas, miuxedavad imisa, pacients Zvlis tvinSi aReniSneba Tu ara blasturi ujredebis arseboba, ewyeba qimioTerapia AML-BFM 2004-is mixedviT.

- 40 -

statistikurma monacemebma, romelic eyrdnoba BFM jgufis mier Catarebul analizs 1987 wlidan dRemde, uCvena, rom pacientebs izolirebuli mielosarkomiT qimioTerapiis fonze unviTardebaT mwvave mieloiduri leikemia (Zvlis tvinis doneze). aRniSnulma analizma aseve aCvena, rom mielosarkomiT daavadebul pacientebs aqvT cudi prognozi da warmoadgenen recidivis ganviTarebis maRal risks. pacientebis 70%-ma aCvena lokaluri an kombinirebuli recidivi.

mielosarkomiT daavadebul pacientebs, sistemuri qimioTerapiuli mkurnalobis Semdeg, utardebaT lokaluri radioTerapia doziT 20-30 grei.

mwvave mieloiduri leikemia da mielodisplaziuri sindromi

mwvave mieloiduri leikemia mielodisplaziuri sindromisagan gansxvavdeba biologiuri maxasiaTeblebiT da Zvlis tvinSi blasturi ujredebis procentuli SemadgenlobiT. Mwvave mieloiduri leikemiis diagnozi definicirdeba mxolod maSin, rodesac pacients Zvlis tvinSi aReniSneba >20% blastebis raodenoba maSin, rodesac mielodisplaziuri sindromis dros blastebis raodenoba meryeobs 10%-dan 20 %-mde. yuradsaRebia morfologiuri maxasiaTeblebi, romlebic mielodisplaziis dros gamovlindeba erTi an samive hemopoezuri ganStoebis displaziiT, romelic axali mieloiduri leikemiebis SemTxvevaSi iSviaTia. mesame mniSvnelovani ganmasxvavebeli maxasiaTebelia molekuluri translokaciebi blastur ujredebSi.

yoveli pacientis Sefaseba, saboloo diagnozi da Casatarebeli Terapiis strategia unda SeTanxmdes mielodisplaziuri sindromis samecniero centrTan, sadac aseve igzavneba Zvlis tvinis aspiratis da periferiuli sisxlis nacxebi. aRniSnuli samecniero centri cnobilia EWOG-MDS-Studie-s saxelwodebiT. misi saTao ofisi imyofeba q. fraiburgSi prof. nimaieris xelmZRvanelobiT.

- 41 -

Sereul ujredovani leikemia da bifenotipuri mwvave leikemiebi

mwvave Sereul ujredovani da bifenotipuri leikemiebis marTvis menejmenti AML-BFM 2004-Si warmodgenilia Semdeg cxrilSi:

zemoT aRniSnuli gadawyvetilebebis miReba xdeba protokolis centralur koordinatorTan SeTanxmebiT.

AML-BFM-Terapia

pasuxi Terapiaze

Acudi

remisia

ALL-BFMTerapia

PpasuxiTerapiaze

cudi

remisia

cudi/parcialurida/ant(9; 22)

MPO, EST (-) cytCD3, CD79a, CD22MPO EST (+)aueris Cxirebi

CD34/CD19/CD10 CD34/CD3/CD8CD13/CD33/7.1CD34/CD13/CD33

M morf.limfoiduri

morf.mieloiduri

AML TerapiaHR Terapia

ALL TerapiaprotokoliIIAML Terapia/ALL HR Terapia

Rerovani ujredis gadanergva

roca ver xdeba saboloo diferencireba

roca ver xdeba saboloo diferencireba

- 42 -

citostatiuri preparatebi da maTi daxasiaTeba

2-CDAwarmoadgens antimetabolits, kerZod, pirimidinis antagonists. 2-CDA iSifreba, rogorc 2 qloro-2-deoqsiadenozini da warmoadgens deoqsiadenozinis analogs. misi komerciuli saxeli aris litaki (Litak). medikamenti gamodis 2mg/ml da 10mg/5ml ampulebis saxiT. infuziis win igi ixsneba NaCl 0,9%-Si.

gverdiTi movlenebi: Rrma mielosupresia da kumulaciuri Trombocitopenia, granulocitopenia, cxeleba, infeqciebi, sisuste, Rebineba, egzanTema, Tavis tkivili, lokaluri reaqciebi, Seqcevadi hepaTopaTia.

ARA-Canalogebia: aleqsani, citozari, citarabini. igi warmoadgens antimetabolits, kerZod, pirimidinis antagonists. medikamenti gamoiyeneba, rogorc intravenurad, aseve intramuskularulad, intralumbalurad da kanqveS. medikamenti gamodis 100, 500 da 1000mg flakonebis saxiT.

gverdiTi movlenebi: mielosupresia, mukozitebi, enteriti, eriTema, cxeleba, mialgia, Zvlebis da saxsrebi tkivili, RviZlis funqciebis darRveva, Zlieri Rebineba da gulisreva.

maRaldozirebuli citozaris xmarebis SemTxvevaSi gansakuTrebiT vlindeba Semdegi gverdiTi movlenebi:

koniuqtiviti, gulis gamtarebel sistemaSi darRvevebi upiratesad taqikardia, somnolencia, cerebraluri ataqsia, afazia, nistagmi, periferiuli neiropaTia.

nistagmis gamoxatvis SemTxvevaSi citozaris infuzia wydeba, raTa pacienti davicvaT Tavis tvinis mZime dazianebisagan (purkinies ujredebis nekrozi).

L-DNR (Liposomal Daunorubicin)miekuTvneba antraciklinebis jgufs (citostatiuri antibiotiki). liposomaluri daunorubicini warmoadgens daunorubicinis ZiriTad formulas damatebuli liposomaluri transportirebuli sistema. Misi komerciuli saxelwodebaa Daunoxome da gamodis 50mg flakonis saxiT.

gverdiTi movlenebi: gadasxmis momentSi SesaZloa gamovlindes welis tkivili da alergiuli temperatoruli reaqcia. Zogadad ki mas axasiaTebs sisuste, Tavis tkivili, Tmis cvena, pancitopenia,

- 43 -

transaminazebisa da tutefosfatazebis momateba. medikamentis xmarebisas SesaZloa gamovlindes mwvave da qronikuli kardiotoqsiuroba kardiomiopaTiiT, ris gamoc medikamentis xmarebisas aucilebelia gulis funqciebis Seswavla eleqtrokardiogramiTa da eqokardiografiiT. gansakuTrebuli mniSvneloba eniWeba gulis kumSvadobis funqciis Seswavlas.

medikamentis xmarebisas yuradsaRebia misi eqstravazacia flebitebis da nekrozis ganviTarebiT, ris gamoc medikamenti gadasxmul unda iqnas centraluri venis kaTeteriT.

liposomaluri daunorubicinis xmarebisas yovelTvis isazRvreba kumulaciuri doza iseve, rogorc sxva antraciklinebis gamoyenebisas da igi ar unda aRematebodes 240mg/m2-s. liposomaluri daunorubicinis dozis reducireba an misi Sewyveta xdeba mxolod im SemTxvevaSi, rodesac pacients gamoexateba mZime mwvave kardiomiopaTia. msubuqad gamoxatuli ariTmiebi ar aris Cveneba medikamentis moxsnis an reducirebisa.

Etopozidwarmoadgens podofilotoqsins. gamodis 100mg an 50mg ampulebis saxiT.

gverdiTi movlenebi: medikamentis uSualod gadasxmisas pacients SeiZlebagamoexatos alergiuli reaqciebi anafilaqsiuri reqciis saxiT, mZime flebitiT, kanze gamonayariT. zogadad ki medikaments axasiaTebs mielosupresia, Rebineba da gulisreva, alopecia. iSviaTad vlindeba periferiuli neiropaTia, mukoziti, cxeleba, Tavis tkivili da qolestazi.

Idarubicin (IDR)miekuTvneba citostatiuri antibiotikebis – antraciklinebis jgufs. gamodis 5 an 10mg flakonebis saxiT. misi komenrciuli saxelia Zavedos.

gverdiTi movlenebi: mwvave da qronikuli kardiotoqsiuroba kardiomiopaTiiT. aRniSnuli garTulebis gamo pacients utardeba kontroli ZiriTadad gulis kumSvadobis funqciisa. mielosupresia, flebitebi, mukoziti, Rebineba, alopecia, RviZlis funqciebis darRveva SesaZloa moyves medikamentis xmarebas.

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Mitoxantron (Mitox)warmoadgens antracinoderivats. gamodis 20, 25, 30mg flakonebis saxiT. sinaTlis mimarT aramdgradia misi gaxsna SesaZlebelia 50ml an 100ml 0,9% NaCl-Si an 5% glukozaSi.

gverdiTi movlenebi: igivea, rac sxva antraciklinebis.

6-Thioguanin (TG)miekuTvneba antimetabolitur preparatebs da warmoadgens purinis antagonistebs. gamodis 40mg abis saxiT da ixmareba oralurad.

gverdiTi movlenebi: Rebineba, gulisreva, mukoziti, diarea, hepatotoqsiuroba.

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qimioTerapiis mogvianebiTi garTulebebimwvave mieloiduri leikemiiT daavadebul pacientebs qimioTerapiis mogvianebiTi garTulebis saxiT uxSiresad aReniSnebaT:

- qronikuli kardiomiopaTia- qronikuli hemoragiuli cistiti- ganayofierebis unaris daqveiTeba

sxivuri Terapiis gverdiTi movlenebi da garTulebebimwvave garTulebebidan cns dazianebis SemTxvevaSi pacients SesaZloa gamouvlindes Tavis tkivili, Rebineba, Zilianoba, da zogadad encefalopaTiis movlenebi. aRniSnul SemTxvevaSi pacients eZleva deqsazoni 5-7 dRis ganmavlobaSi doziT 0,5mg/kg/dR.

cns dasxivebis mogvianebiT garTulebas ki warmoadgens Tavis tvinis meoradi simsivneebi.

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damxmare Terapiuli RonisZiebebi

pacients, romelsac aqvs mwvave mieloiduri leikemiis diagnozi, yvela SemTxvevaSi utardeba maRaldozirebuli Zvlistvinovan toqsiuri qimioTerapia, ris gamoc igi uxSiresad imyofeba imuno da mielosupresiul mdgomareobaSi. mwvave mieloiduri leikemiis mkurnaloba zemoaRniSnulidan gamomdinare SesaZloa Caataros mxolod pediatrma-onkologma adeqvaturi codniTa da gamocdilebiT. mkurnaloba unda mimdinareobdes multidisciplinarul bavSvTa klinikaSi, sadac SesaZlebelia garTulebebis marTvaSi aqtiuri monawileoba miiRon sxva specialobis pediatrebma.

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infeqciebi

infeqciebis profilaqtikainfeqciebis profilaqtika pirvel rigSi moicavs higienur mdgomareobas klinkiaSi, sadac tardeba aqtiuri maRaldozirebuli qimioTerapia. higienuri procedurebis dacva exeba pacientis oTaxs, haers, pirveladi moxmarebis sagnebs, wyals da sapons.

infeqciuri statusis inicialuri Semowmeba da Semdgomi skriningidiagnozisas pacientebs unda Cautardes serologiuri kvlevebi herpesis, citomegalovirusis, ebStein-baris da virusuli hepatitis mimarT. romelime aRniSnuli virusis aqtiuri formis aRmoCenisas pacients unda Cautardes Sesabamisi etiotropiuli (Tu es ukanaskneli arsebobs) mkurnaloba da serologiuri skriningi aqtiuri qimioTerapiisa da dacviTi Terapiebis dros.

antibaqteriuli profilaqtikamwvave mieloiduri leikemiiT daavadebuli pacientebi mkurnalobis dros warmoadgenen infeqciuri garTulebebis maRali riskis jgufis pacientebs, ris gamoc isini yovelTvis Rebuloben antibaqteriul profilaqtikur preparatebs.

antibaqteriuli profilaqtika ZiriTadad moicavs oralur antibiotikebs: kolistini, parmomicini doziT 100 000 erTeuli/kg/dR 3 miRebaze.

peniciliniT profilaqtika seleqtiuria da utardeba mxolod im pacientebs, romlebmac miiRes HAM Terapia, rameTu maRaldozirebuli citozaris gamoyeneba erTmniSvnelovnad zrdis Streptococcus viridans–iT gamowveul pnevmoniebs. penicilini iniSneba 100 000-250 000 erTeuli/kg/dR. aqve unda aRiniSnos, rom randomizirebuli kvlevebis Sedegad profilaqtikurma penicilinma ar uCvena maRali efeqturoba da pacientebis umravlesobaSi ganviTarda Streptococcus viridans–iT gamowveuli pnevmonia.

Pneumocystis carinii-s profilaqtikayvela pacients utardeba trimetoprimiT 5mg/kg/dR 2 miRebaze. kviraSi 3 dRe. trimetoprimis miReba grZeldeba qimioTerapiis damTavrebisas da damTavrebis Semdeg xangrZlivobiT 3 Tve.

antifungaluri profilaqtikarogorc aRvniSneT, mwvave mieloiduri leikemiebis dros pacientebi uxSiresad imyofebian xangrZliv mielosupresiul mdgomareobaSi, ris gamoc isini ganekuTvnebian invaziuri sokovani infeqciebis Zalian maRal risks. Sesabamisad antifungaluri profilaqtika moicavs mTlian intensiur qimioTerapias da tardeba flukonazoliT 8mg/kg/dR, maqsimaluri doza 400mg/dR, an intrakonazoliT 2,5mg/kg x2 dReSi. es ukanaskneli gansakuTrebiT mniSvnelovania im klinikebisaTvis, sadac higienuri da ekologiuri pirobebis gamo maRalia aspergilozis ganviTarebis riski. am mxriv, itrakonazolis gamoyeneba profilaqtikis mizniT ufro efeqturi iqneba saqarTveloSi.

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infeqciuri garTulebebis diagnostika neitropeniul pacientebSi

baqteriuli infeqciebis diagnostikaigivea, rac neitropeniuli cxelebis diagnostika. ix. qvemoT.

invaziuri sokovani infeqciebis diagnostika moicavs:

- sisxlSi kandidasa da aspergilas antigenebis gamoyofas. Sedegebi sarwmunoa, rodesac kvleva tardeba ELISA da PCR-is meTodiT;

- radiologiur kvlevebs, kerZod ki, Tavis tvinis, gul-mkerdisa da muclis Rrus kompiuterul tomografias;

- dadasturebuli invaziis lokalizaciis SemTxvevaSi sasurvelia Catardes biofsia Semdgomi histologiuri kvleviT.

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empiriuli mkurnaloba

neitropeniuli cxeleba

diagnostika

1. anamnezi, detaluri fzikaluri gamokvleva, pulsi, sunTqvis sixSire da arteriuli wneva

2. sisxlis saerTo analizi, sisxlis bioqimiuri analizi, anTebis sawinaaRmdego cilis gansazRvriT

3. sisxlis kulturis Seswavla baqteriologiurad4. respiratoruli simptomebis gamovlenisas virusuli

diagnostika5. Sardis kulturis gamokvleva

Semdgomi diagnostika damokidebulia klinikur simptomebze(mag., gl-mkerdis rendgeni respiratoruli simptomebis SemTxvevaSi)

dauyovnebliv daiwye empiriuli antibaqteriuli Terapia klinikuri mdgomareobisa da sasicocxlo funqciebis monitoringiT.

gaumjobeseba 48-72 sT-is Semdeg:

gaagrZele Terapia hemopoezis regeneraciamde

ganmeorebiTi cxeleba da neitropenia:

re-diagnostika gul-mkerdisa da muclis kompiuteruli tomografiiT;

modifikacia empiriuli antibiotikuri Terapiis;

empiriuli antifungaluri Terapia.

ar aris gaumjobeseba 48-72 sT-is Semdeg:

re-diagnostika gul-mkerdisa da muclis kompiuteruli tomografiiT;

modifikacia empiriuli antibiotikuri Terapiis;

empiriuli antifungaluri Terapia.

gaumjobeseba:

gaagrZele Terapia hemopoezis regeneraciamde

ar aris gaumjobeseba an ganviTarda axali neitropeniuli cxelebis epizodi:gaagrZele diagnostika klinikuri niSnebis mixedviT;modifikacia inicialuri empiriuli Terapiis

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empiriuli antibaqteriuli TerapiaTerapia 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

antibaqteriuli oqmis modifikacia gamovlenili klinikuri niSnebisa da infeqciebis lokalizaciebis mixedviT

sisxlis kultura:

• gramdadebiTi baqteriis aRmoCenisas – dauyovnebliv glikopeptidi

• gramnegatiuri baqteriebis aRmoCenisas – karbapenemi / aminoglikoziti

• sokovani infeqciis aRmoCenisas – antifungaluri Terapia

mukoziti/gingiviti:

• mukozitisas da gingivitisas – metronidazoli (mosalodneli anaerobuli infeqcia); acikloviri (herpes simpleqsi)

• ezofatisisas – amfotericini B, acikloviri

abdominaluri, perireqtaluri da perianaluri tkivilebi

• metronidazoli, glindamicini, glikopeptidi

axali fokaluri pulmonaruli infiltracia

• antifungaluri Terapia da makrolidebi (mikoplazma, qlamidia, legionela) an qinolonis jgufis preparatebi

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axali intersticiuli pnevmonia

• empiriuli Terapiuli dozebi trimetoprimisa

sinusiti / intranazaluri wyluli

• amfotericin B

sefsis-sindromi, septiuri Soki

• karbapenemi / aminoglikozidi / glikopeptidi

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invaziuri fungaluri infeqciebis mkurnaloba

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.

fungaluri infeqciebis mkurnalobisTvis saWiro preparatebi da dozireba

kandidaTi gamowveuli fungaluri infeqciebi:

• amfotericin B: 0,7mg/kg – 1mg/kg intravenurad• flukonazoli: 12 mg/kg. maqsimaluri 16mg/kg., maqsimaluri

sadReRamiso dozaa 800 mg/dR intravenurad an oralurad im pacientebSi, visac ar aqvs darRveuli Sewovis procesebi

• vorikonazoli: dRe 1. 2x 6mg/kg/dR. dRe 2-dan – 2x 4mg/kg/dR. bavSvebi, romelTa asaki >13 w. dRe 1 – 2x 400mg/dR. dRe 2 – 2x 200 mg/dR

• liposomaluri amfotericini B: 3-5 mg/kg. gamoiyeneba amfotericin B-s gamoxatuli toqsiurobis dros

• kaspofungini: 1-1,5mg/kg/dR. maqsimaluri dRiuri dozaa 50mg/m2

aspergiloziT gamowveuli fungaluri infeqciebi:

• amfotericin B: 0,7mg/kg – 1mg/kg intravenurad• liposomaluri amfotericini B: 3-5 mg/kg. gamoiyeneba amfotericin

B-s gamoxatuli toqsiurobis dros

• vorikonazoli: dRe 1. 2x 6mg/kg/dR. dRe 2-dan – 2x 4mg/kg/dR. bavSvebi, romelTa asaki >13 w. dRe 1 – 2x 400mg/dR. dRe 2 – 2x 200 mg/dR

• kaspofungini: 1-1,5mg/kg/dR. maqsimaluri dRiuri dozaa 50mg/m2

• intrakonazoli: 2x 5mg/kg

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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. 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

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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.

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urgentuli garTulebebi da maTi marTva

hiperleikocitozi

hiperleikozitozis SesaZlo garTuleba aris leikostazi Semdgomi sisxldenebiTa da sisxlCaqcevebiTa filtvebSi, cns-sa da TirkmlebSi. Tirkmlis funqciuri dazianeba aseve viTardeba mwvave lizisis sindromis dros, romelic aseve uxSiresad dakavSirebulia hiperleikocitozTan. aRniSnuli garTuleba ZiriTadad vlindeba, rodesac sawyisi leikocitebis raodenoba 100 000/mkl-ze metia, Tumca mwvave promielocituri leikemiis dros hemostazis darRveva viTardeba 10 000/mkl leikocitebzec ki. es ukanaskneli gamowveulia blasturi ujredebidan gamoTavisuflebuli Tromboplastinis maRali donis SeqmniT Semdgomi disiminirebuli sisxlZarRvTa Sida Sededebis sindromis ganviTarebiT; monoblasturi leikemiebis SemTxvevaSi leikostazisa da reologiuri cvlilebebis gamovlena ufro xSirad viTardea, roca leikocitebis sawyisi raodenoba 100 000/mkl -ze metia maSin, roca M1 M2 formebis dros es garTuleba aRiniSneba 150 000/mkl–ze meti leikocitebis dros.Eleikostazis simptomebi SesaZloa gamovlindes taqipnoeTi, dispnoeTi da cianoziT, rodesac adgili aqvs pulmonalur infiltracias. cns infiltraciis dros vlindeba ataqsia, nistagmi, stupori. leikostazis diagnozis dasmis Semdeg pacientebis mwvave mieloiduri leikemiiT saWiroeben leikoferezis Catarebas. Leikoferezis Cvenebas warmoadgens inicialuri leikocitebis raodenoba = 200 000/mkl. gamonakliss warmoadgens monoblasturi leikemia, sadac leikoferezze sakiTxi dgeba maSin, rodesac leikocitebi = 100 000/mkl-s.

hiperleikocitozi leikostazis sindromis gareSe definicirdeba, roca inicialuri blastebis raodenoba > 50 000/mkl-ze. aRniSnul SemTxvevaSi pacientTan tardeba Semdegi RonisZiebebi:

1. isazRvreba sruli koagulograma 2. saWiroebis SemTxvevaSi, pacients utardeba intensiuri Terapia3. hidratacia adeqvaturi balansirebiT4. Sardis alkalinizacia5. alopurinolis an rasburikazes daniSvna6. Tu gemoglobinis raodenoba ar aris kritikuli da pacients

klinikurad ar aqvs gamoxatuli hipoqsiis niSnebi, maqsimalurad Tavs vikavebT eriTrocitebis transfuziisgan. Trombopeniis SemTxvevaSi xdeba Trombocitebis transfuzia.

7. pacients eniSneba hidroqsiurea 20mg/kg/dR an citozari 40 mg/m2/dR. SesaZloa maTi erTdrouli gamoyeneba.

8. diagnostikuri lumbaluri punqcia ar keTdeba manam, sanam ar moxdeba blastebis reduqcia.

9. hiperleikocitozisa da mosalodneli leikostazis SemTxvevaSi antraciklinebi ar iniSneba.

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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) > 1500

• 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

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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

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).

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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:

- 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

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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.

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

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- 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.

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.

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- 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 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

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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.

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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

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Trombocitebis transfuzia

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

- sefsisi- disiminirebuli sisxlZarRvTa Sida

koagulopaTia- 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

- 65 -

qimioTerapiuli blokebis dokumentaciakonkretuli pacientebisaTvis

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klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------

ARA-C: 100mg/m2/dR. dReE1, 2.48 saaTiani infuzia


L-DNR: 80mg/m2/dR. dRe 3, 5, 7. infuzia 120 wT



induqcia

l.p.

Zvt.p.

dRe

- 67 -

induqcia

klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------

l.p.

Zvt.p.

dRe






- 68 -

klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------

l.p.

Zvt.p.

dRe






- 69 -

klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------

ARA-C: 500mg/m2/dR. dRe 1-4. 96 sT-iani uwyveti infuzia

2DCA: 6mg/m2. dRe 1, 3. infuzia 30 wT.

IDR: 7mg/m2/dR. dRe 3, 5. infuzia 60 wT.l.p.

Zvt.p.

dRe

- 70 -

klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------

HD ARA-C: 1gr/m2. dRe 1-3. 12 x. 3 sT-iani infuzia

Mitoxantron: 10mg/m2/dR. dRe 3, 4. infuzia 30 wT.

ARA-C: lumbalurad. dRe 1, 6.

l.p.

Zvt.p.

dRe

- 71 -

ARA-C: 3gr/m2. dRe 1-3. 12 sT-Si x. infuzia 3 sT.

Mitox: 10mg/m2/dR. dRe 3, 4. infuzia 30 wT.

ARA-C: lumbalurad. dRe 1

klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------induqcia

l.p.

Zvt.p.

dRe

- 72 -

HD ARA-C: 3gr/m2. dRe 1-3. 12 x. 3 saaTiani infuzia

Etopozid: 125mg/m2/dR. dRe 2, 3, 4, 5. infuzia 60 wT.

ARA-C: lumbalurad. dRe 1.

klinika: -----------------------------------

pacienti: ---------------------------------

dab.TariRi:------------------------------

wona:-------------- simaRle: --------------

sxeulis farTi: ------------------

l.p.

Zvt.p.

dRe

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literatura

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