{"id":1090,"date":"2016-12-08T23:01:33","date_gmt":"2016-12-08T22:01:33","guid":{"rendered":"http:\/\/www.newslab.sk\/2016\/12\/08\/hodnotenie-odpovede-na-liecbu-u-pacientov-s-chronickou-myelocytovou-leukemiou-liecenych-s-inhibitormi-tyrozinkinazy\/"},"modified":"2017-10-04T14:36:58","modified_gmt":"2017-10-04T12:36:58","slug":"evaluation-of-therapeutic-response-in-patients-with-chronic-myeloid-leukemia-treated-with-tyrosine-kinase-inhibitors","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/evaluation-of-therapeutic-response-in-patients-with-chronic-myeloid-leukemia-treated-with-tyrosine-kinase-inhibitors\/","title":{"rendered":"Evaluation of therapeutic response in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf \r\nattachment at the end of the paper. <\/span><\/strong><\/pre>\n
 <\/p>\n
\u00da<\/strong>vod<\/strong><\/p>\n
Chronick\u00e1 myelocytov\u00e1 leuk\u00e9mia (CML) je klon\u00e1lna porucha hematopoetickej kme\u0148ovej bunky s diferenci\u00e1ciou preva\u017ene do myeloidn\u00e9ho radu. Typick\u00fdm cytogenetick\u00fdm \u00a0n\u00e1lezom je pr\u00edtomnos\u0165 tzv. chromoz\u00f3mu Philadelphia (Ph), ktor\u00fd je v\u00fdsledkom recipro\u010dnej translok\u00e1cie medzi dlh\u00fdmi ramenami chromoz\u00f3mov 9 a 22, t(9;22)(q34;q11), ktor\u00e1 je identifikovate\u013en\u00e1 u viac ako 95 % chor\u00fdch s CML. Produktom tejto translok\u00e1cie je f\u00fazny g\u00e9n B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>B<\/em>L<\/em>, ktor\u00fd k\u00f3duje chim\u00e9rick\u00e9 prote\u00edny (p190, p210, p230). Naj\u010dastej\u0161ie sa vyskytuj\u00facim z nich je prote\u00edn p210 s kon\u0161titut\u00edvnou aktivitou tyroz\u00ednkin\u00e1zy \u00a0(TK). Jeho \u00a0podiel \u00a0na patogen\u00e9ze CML a v\u00fdslednom leukemickom fenotype sa v s\u00fa\u010dasnosti \u00a0pova\u017euje za k\u013e\u00fa\u010dov\u00fd (1). Pribli\u017ene u 5 % pacientov s CML nie je mo\u017en\u00e9 dok\u00e1za\u0165 Ph chromoz\u00f3m, ale maj\u00fa dok\u00e1zan\u00fd f\u00fazny g\u00e9n B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>B<\/em>L<\/em>. Ochorenie sa ozna\u010duje ako CML Ph negat\u00edvna, B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>BL <\/em>pozit\u00edvna (Ph-, B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>B<\/em>L<\/em>+).<\/p>\n
Chronick\u00e1 myelocytov\u00e1 leuk\u00e9mia tvor\u00ed pribli\u017ene 15 \u2013 20 % zo v\u0161etk\u00fdch pr\u00edpadov leuk\u00e9mi\u00ed dospel\u00fdch s incidenciou 1 \u2013 1,5 pr\u00edpadu\/100 \u00a0000 obyvate\u013eov za rok. Ochorenie \u00a0sa vyskytuje vo v\u0161etk\u00fdch vekov\u00fdch skupin\u00e1ch, ale v\u00fdskyt pomaly narast\u00e1 s vekom. Medi\u00e1n veku v \u010dase diagn\u00f3zy sa uv\u00e1dza 61 rokov, v klinick\u00fdch \u0161t\u00fadi\u00e1ch dokonca iba 58 rokov. Mu\u017ei \u00a0s\u00fa o nie\u010do \u010dastej\u0161ie \u00a0postihnut\u00ed \u00a0ako \u017eeny (1,4 : 1).<\/p>\n
Hoci \u00a0k z\u00e1kladn\u00fdm \u00a0vy\u0161etreniam \u00a0na d\u00f4kaz ochorenia CML zara\u010fujeme fyzik\u00e1lne vy\u0161etrenia \u00a0a vy\u0161etrenia krvn\u00e9ho obrazu, cytogenetick\u00e9 a molekulov\u00e9 vy\u0161etrenie je k\u013e\u00fa\u010dov\u00e9 na potvrdenie diagn\u00f3zy. V\u00fdznamn\u00fd je predov\u0161etk\u00fdm d\u00f4kaz onkog\u00e9nu\u00a0 B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>B<\/em>L<\/em>, ktor\u00fd k\u00f3duje u\u017e spomenut\u00fd fosfoprote\u00edn s tyroz\u00ednkin\u00e1zovou aktivitou. Cie\u013eom lie\u010dby CML je dosiahnu\u0165 kompletn\u00fa molekulov\u00fa remisiu, t. j. stav, \u00a0ke\u010f nie je mo\u017en\u00e9 detegova\u0165 ochorenie ani na molekulovej \u00farovni.<\/p>\n
C<\/strong>i<\/strong>e<\/strong>l<\/strong>e a mo\u017enosti lie\u010dby CML<\/strong><\/p>\n
Hlavn\u00fa\u00a0 skupinu \u00a0liekov, ktor\u00fdmi sa lie\u010dia pacienti s CML v s\u00fa\u010dasnosti, predstavuj\u00fa inhib\u00edtory tyroz\u00ednovej kin\u00e1zy (TKI), ktor\u00fdch zavedenie \u00a0do lie\u010dby znamenalo revol\u00faciu v lie\u010dbe CML. Imatinib mesyl\u00e1t (IM) je pova\u017eovan\u00fd za liek prvej l\u00ednie u chor\u00fdch s novodiagnostikovanou CML v chronickej f\u00e1ze ochorenia a cie\u013eom \u00a0lie\u010dby je dosiahnutie \u00a0ve\u013ekej molekulovej odpovede (MMR). Dosiahnutie MMR do 1 roka sa pova\u017euje za v\u00fdznamn\u00fd prediktor hlbokej molekulovej odpovede.<\/p>\n
S cie\u013eom zv\u00fd\u0161enia po\u010dtu odpoved\u00ed, ale aj prekonania rezistencie na imatinib sa za\u010dal v\u00fdvoj nov\u00fdch \u00a0TKI. V skuto\u010dnosti \u00a0tieto lieky dok\u00e1zali r\u00fdchlej\u0161ie navodenie \u00a0vy\u0161\u0161ieho po\u010dtu cytogenetick\u00fdch a molekulov\u00fdch remisi\u00ed. S t\u00fdmito cie\u013emi boli vyvinut\u00e9 dve nov\u00e9 TKI (dasatinib a nilotinib), t. j. druhogenera\u010dn\u00e9 TKI.<\/p>\n
Aj napriek produkcii signifikantne vysok\u00e9ho po\u010dtu lie\u010debn\u00fdch odpoved\u00ed pri CML, pribli\u017ene u 25 \u2013 30 % pacientov sa vyvinie rezistencia \u00a0na lie\u010dbu. Jej naj\u010dastej\u0161ou pr\u00ed\u010dinou je vznik alebo n\u00e1rast mut\u00e1ci\u00ed v B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>BL <\/em>kin\u00e1zovej dom\u00e9ne, ktor\u00e1 je aj naj\u010dastej\u0161ie \u00a0uv\u00e1dzanou \u00a0pr\u00ed\u010dinou \u00a0z\u00edskanej rezistencie na imatinib. Mut\u00e1cia T315I predstavuje v\u00fdznamn\u00fd \u00a0klinick\u00fd probl\u00e9m, preto\u017ee je rezistentn\u00e1 k v\u0161etk\u00fdm komer\u010dne dostupn\u00fdm TKI 1. a 2. gener\u00e1cie. Mut\u00e1cia je spojen\u00e1 s vysokoagres\u00edvnym priebehom ochorenia a zlou progn\u00f3zou, ak ned\u00f4jde k r\u00fdchlemu terapeutick\u00e9mu z\u00e1sahu a zmene terapie (ponatinib, danusertib).<\/p>\n
Alog\u00e9nna transplant\u00e1cia kme\u0148ov\u00fdch krvotvorn\u00fdch buniek je st\u00e1le pova\u017eovan\u00e1 za jedin\u00fa dok\u00e1zate\u013en\u00fa mo\u017enos\u0165 eradik\u00e1cie mal\u00edgneho klonu. V s\u00fa\u010dasnosti je posunut\u00e1 \u00a0do 3. a 4. l\u00ednie lie\u010dby po zlyhan\u00ed druhol\u00edniov\u00fdch TKI. Indikovan\u00e1 \u00a0je pacientom, ktor\u00ed s\u00fa rezistentn\u00ed na lie\u010dbu alebo maj\u00fa intoleranciu aspo\u0148 k jedn\u00e9mu z TKI 2. gener\u00e1cie.<\/p>\n
V r\u00e1mci projektu medzin\u00e1rodnej \u00a0spolo\u010dnosti pre diagnostiku a lie\u010dbu CML ELN (European \u00a0LeukemiaNet) \u00a0vznikol projekt EUTOS for CML (The European Treatment Outcome \u00a0Study for CML), do ktor\u00e9ho s\u00fa od roku 2009 zara\u010fovan\u00ed aj pacienti z \u010ceskej a Slovenskej republiky. Ide o register CAMELIA a INFINITY. V \u010dl\u00e1nku prin\u00e1\u0161ame ELN odpor\u00fa\u010dania pre mana\u017ement pacientov s CML z roku 2013 (2), ktor\u00e9 s\u00fa tre\u0165ou verziou odporu\u010den\u00ed \u00a0z roku 2006 (3) a 2009 (4).<\/p>\n
 <\/p>\n
C<\/strong>y<\/strong>t<\/strong>og<\/strong>e<\/strong>n<\/strong>e<\/strong>t<\/strong>i<\/strong>c<\/strong>k<\/strong>\u00e9 vy\u0161etrenie<\/strong><\/p>\n
Cytogenetick\u00e9 vy\u0161etrenie je esenci\u00e1lne na potvrdenie diagn\u00f3zy CML a monitorovanie cytogenetickej remisie ochorenia.
\nP<\/em>h pozit\u00edvna CML. <\/em>V \u010dase diagn\u00f3zy m\u00e1 95 % pacientov s CML v aspir\u00e1te kostnej drene pr\u00edtomn\u00fd Ph chromoz\u00f3m. Asi u 5 \u2013 10 % Ph pozit\u00edvnych pacientov Ph chromoz\u00f3m vznikne variantnou komplexnou translok\u00e1ciou, do ktorej je zapojen\u00fdch tri a viac chromoz\u00f3mov.<\/p>\n
P<\/em>h negat\u00edvna CML. <\/em>Pribli\u017ene 5 % pacientov s CML nem\u00e1 pr\u00edtomn\u00fd Ph chromoz\u00f3m, ale je pr\u00edtomn\u00e1 \u00a0g\u00e9nov\u00e1 \u00a0f\u00fazia B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>B<\/em>L<\/em>. Ide o kryptick\u00fa translok\u00e1ciu t(9;22), ktor\u00e1 je cytogeneticky nedetegovate\u013en\u00e1. Patologick\u00fd klon je Ph negat\u00edvny (Ph-) a z\u00e1rove\u0148 B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>BL <\/em>pozit\u00edvny.<\/p>\n
Okrem translok\u00e1ciet(9;22) sa m\u00f4\u017eu vyskytn\u00fa\u0165 aj pr\u00eddavn\u00e9 cytogenetick\u00e9 zmeny, ktor\u00e9 s\u00fa zv\u00e4\u010d\u0161a predzves\u0165ou progresie ochorenia. Del\u00e9cia 9. chromoz\u00f3mu a variantn\u00e9 translok\u00e1cie nemaj\u00fa prognostick\u00fd v\u00fdznam (5), av\u0161ak klon\u00e1lne chromoz\u00f3mov\u00e9 aber\u00e1cie (CCA) v Ph+ bunk\u00e1ch (CCA\/Ph+) maj\u00fa negat\u00edvnu prognostick\u00fa hodnotu, hlavne v pr\u00edtomnosti tzv. \u201emajor zmien\u201c, ako s\u00fa duplik\u00e1cia Ph chromoz\u00f3mu (+Ph); izochromoz\u00f3m 17q; triz\u00f3mia 8; triz\u00f3mia 19 a 21, ale aj strata chromoz\u00f3mu 17p (6, 7).<\/p>\n
Cytogenetick\u00e9 vy\u0161etrenie z kostnej drene (CBA \u2013 chromosome banding analysis) sa pod\u013ea ELN krit\u00e9ri\u00ed vykon\u00e1va v \u010dase diagn\u00f3zy a\/alebo pri monitorovan\u00ed odpovede pacienta na lie\u010dbu v 3., 6. a 12. mesiaci lie\u010dby a\u017e do dosiahnutia kompletnej cytogenetickej remisie (CCyR), n\u00e1sledne ka\u017ed\u00fdch 12 mesiacov. CBA sa vykon\u00e1va aj v progresii ochorenia po\u010das lie\u010dby, pri zlyhan\u00ed lie\u010dby, v pr\u00edpade v\u00fdskytu myelodyspl\u00e1zie alebo pr\u00eddavn\u00fdch aber\u00e1ci\u00ed v Ph negat\u00edvnom klone. Pri v\u00fdskyte varovn\u00fdch znakov ELN odpor\u00fa\u010da vy\u0161etri\u0165 karyotyp \u010dastej\u0161ie spolu s molekulov\u00fdm vy\u0161etren\u00edm (tabu\u013eka 1).<\/p>\n
 <\/p>\n
F<\/strong>IS<\/strong>H (fluorescen\u010dn\u00e1 <\/strong>i<\/em><\/strong>n situ <\/em><\/strong>h<\/strong>yb<\/strong>r<\/strong>idi<\/strong>z<\/strong>\u00e1<\/strong>c<\/strong>i<\/strong>a<\/strong>)<\/strong><\/p>\n
FISH met\u00f3da patr\u00ed medzi molekulovo-cytogenetick\u00e9 \u00a0met\u00f3dy, ktor\u00e9 umo\u017e\u0148uje \u00a0detegova\u0165 \u00a0aj submikroskopick\u00e9 zmeny chromoz\u00f3mov, \u010do v pr\u00edpade CML znamen\u00e1 \u00a0napr\u00edklad identifik\u00e1ciu kryptickej translok\u00e1cie u Ph negat\u00edvnych pacientov, stanovenie typu translok\u00e1cie a identifik\u00e1ciu mikrodel\u00e9ci\u00ed. Z\u00e1rove\u0148 je FISH vy\u0161etrenie schopn\u00e9 identifikova\u0165 patologick\u00fd klon aj v n\u00edzkom percentu\u00e1lnom zast\u00fapen\u00ed. Cie\u013eom FISH vy\u0161etrenia je stanovi\u0165 percentu\u00e1lne \u00a0zast\u00fapenie \u00a0patologick\u00e9ho \u00a0klonu s t(9;22) vo vy\u0161etrovanej popul\u00e1cii buniek (tabu\u013eka 2 a 3).<\/p>\n
FISH vy\u0161etrenie z kostnej drene (KD) sa vykon\u00e1va v \u010dase diagn\u00f3zy, ke\u010f sa ur\u010d\u00ed typ translok\u00e1cie. FISH vy\u0161etrenie je n\u00e1pomocn\u00e9 \u00a0najm\u00e4 vtedy, ak ide o Ph negat\u00edvnu CML (potvrdenie \u00a0kryptickej translok\u00e1cie), alebo ak cytogenetick\u00e9 vy\u0161etrenie nie je mo\u017en\u00e9 \u00a0uskuto\u010dni\u0165. N\u00e1sledne sa FISH vykon\u00e1va pravidelne a\u017e do dosiahnutia kompletnej cytogenetickej remisie (CCyR), potom ka\u017ed\u00fdch 12 mesiacov (tabu\u013eka 1).<\/p>\n
 <\/p>\n
Mol<\/strong>e<\/strong>k<\/strong>ul<\/strong>ov\u00e1 anal\u00fdza<\/strong><\/p>\n
Minim\u00e1lna rezidu\u00e1lna choroba, po\u010det transkriptov B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>B<\/em>L<\/em>, sa sleduje met\u00f3dou \u00a0molekulovej anal\u00fdzy, kvantitat\u00edvnou polymer\u00e1zovou re\u0165azovou reakciou v re\u00e1lnom \u010dase (qRT-PCR). Molekulov\u00fa odpove\u010f stanovujeme na z\u00e1klade hodnotenia pomeru B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>BL <\/em>ku konkr\u00e9tnemu g\u00e9nu, naj\u010dastej\u0161ie A<\/em>BL <\/em>v % pod\u013ea medzin\u00e1rodnej stupnice IS (International Scale). Z\u00e1rove\u0148 je nutn\u00e9 poznamena\u0165, \u017ee po\u010dty k\u00f3pi\u00ed kontroln\u00e9ho g\u00e9nu A<\/em>BL <\/em>v replik\u00e1toch musia ma\u0165 hodnoty > 10 000. Stupnica \u00a0IS bola vyhotoven\u00e1 \u00a0na to, aby sa mohli jednotliv\u00e9 B<\/em>C<\/em>R-ABL \u00a0<\/em>hodnoty z\u00edskan\u00e9 v r\u00f4znych laborat\u00f3ri\u00e1ch navz\u00e1jom zos\u00faladi\u0165 \u2013 pomocou \u00a0\u0161pecifick\u00fdch konverzn\u00fdch faktorov pre dan\u00e9 laborat\u00f3rium.<\/p>\n
IS je zalo\u017een\u00e1 na dvoch definovan\u00fdch hodnot\u00e1ch:<\/strong><\/p>\n
    \n
  • \u0161tandardizovan\u00e1 \u201ebaseline\/v\u00fdchodiskov\u00e1\u201c hodnota, ktor\u00e1 je definovan\u00e1 medi\u00e1nom hladiny B<\/em>C<\/em>R<\/em>–<\/em>A<\/em>BL <\/em>vo v\u010dasnej chronickej f\u00e1ze CML pred lie\u010dbou (IS \u2013 100 %),<\/li>\n
  • zn\u00ed\u017eenie o 3 log (1 000-n\u00e1sobne) \u00a0proti baz\u00e1lnej hodnote \u00a0(IS \u2013 0,1 %) zodpoved\u00e1 ve\u013ekej molekulovej odpovedi (MMR) (8, 9).<\/li>\n<\/ul>\n
    \u00darovne molekulovej odpovede \u00a0pri lie\u010dbe CML s\u00fa uveden\u00e9 na obr\u00e1zku a hodnotenia odpoved\u00ed na lie\u010dbu u pacientov s CML lie\u010den\u00fdch prvo- a druhogenera\u010dn\u00fdmi TKI s\u00fa uveden\u00e9 v tabu\u013eke 2 a 3. V s\u00fa\u010dasnosti \u00a0sa klad\u00fa spr\u00edsnen\u00e9 krit\u00e9ri\u00e1 na monitorovanie hlbokej molekul\u00e1rnej odpovede, ke\u010f\u017ee trval\u00e1 hlbok\u00e1 molekul\u00e1rna odpove\u010f \u00a0je nevyhnutn\u00fdm vstupn\u00fdm\u00a0krit\u00e9riom v klinick\u00fdch sk\u00fa\u0161aniach, ktor\u00e9 sk\u00famaj\u00fa mo\u017enos\u0165 dosiahnutia\u00a0remisie bez lie\u010dby.<\/p>\n
     <\/p>\n
    P<\/strong>r<\/strong>e<\/strong>d<\/strong>an<\/strong>a<\/strong>l<\/strong>y<\/strong>t<\/strong>i<\/strong>c<\/strong>k<\/strong>\u00e9 inform\u00e1cie<\/strong><\/p>\n
    Na cytogenetick\u00e9 a FISH vy\u0161etrenie sa odober\u00e1 5 ml perif\u00e9rnej krvi (PK) alebo kostnej drene (KD) do sk\u00famaviek s hepar\u00ednom l\u00edtnym (LiH).\u00a0Na molekulov\u00e9 vy\u0161etrenie sa odober\u00e1 5 ml PK alebo KD do sk\u00famaviek s EDTA a z\u00e1rove\u0148 3 ml PK alebo KD do TEMPUS sk\u00famaviek, ktor\u00e9 obsahuj\u00fa stabiliza\u010dn\u00fd roztok zamedzuj\u00faci degrad\u00e1cii RNA. Vzorky sa do transportu a po\u010das neho uchov\u00e1vaj\u00fa pri teplote 4 \u2013 10 \u02daC, pri\u010dom je potrebn\u00e9, aby boli vzorky doru\u010den\u00e9 do laborat\u00f3ria \u010do najsk\u00f4r.<\/p>\n
     <\/p>\n
    Literat\u00fara<\/strong>
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    \n2. Baccarani M, Deininger M, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872\u2013884.
    \n3. Baccarani M, Saglio G, Goldman J, et al. European LeukemiaNet. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108(6):1809\u20131820.
    \n4. Baccarani M, Cortes J, Pane F, et al. European LeukemiaNet. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27(35):6041 6051.
    \n5. Fabarius A, Leitner A, Hochhaus A, et al. Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung (SAKK) and the German Study Group. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood. 2011;118(26):6760\u20136768.
    \n6. Katarjian HM, Shah NP, Cortes JE, et al. Dasatinib or imatinib in newly diagnosed chronic phase chronic myeloid leukemia: 2-years follow up from a randomized phase 3 trial (DASISION). Blood. 2012;119(5):1123\u20131129.
    \n7. Faber E, Muzik J, Koza V, et al. Treatment of consecutive patients with chronic myeloid leukaemia in the cooperating centres from the Czech Republic and the whole of Slovakia after 2000 \u2013 a report from the population-based CAMELIA Registry. Eur J Haematol. 2012;87(2):157\u2013168.
    \n8. Branford S, Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. Methods Mol Med. 2008;125:69\u201392.
    \n9. Branford S. Monitoring after successful therapy for chronic myeloid leukemia. Hematology 2012, ASH. 2012;105\u2013110<\/p>\n","protected":false},"excerpt":{"rendered":"
    *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   \u00davod Chronick\u00e1 myelocytov\u00e1 leuk\u00e9mia (CML) je klon\u00e1lna porucha hematopoetickej kme\u0148ovej bunky s diferenci\u00e1ciou preva\u017ene do myeloidn\u00e9ho radu. Typick\u00fdm cytogenetick\u00fdm \u00a0n\u00e1lezom je pr\u00edtomnos\u0165 tzv. chromoz\u00f3mu Philadelphia (Ph), ktor\u00fd je v\u00fdsledkom<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[290],"tags":[657,690,658],"class_list":["post-1090","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-chronic-myeloid-leukemia","tag-evaluation-of-treatment-response","tag-tyrosine-kinase-inhibitors","typ_clanku-review-article"],"acf":{"abstrakt":"
    Advances in chronic myeloid leukemia (CML) treatment have markedly changed with the introduction of tyrosine kinase inhibitors (TKI). Regular updating of patient management and treatment recommendations is an absolute must. Current recommendations in compliance with European LeukemiaNet (ELN) date back to 2013 and represent the third version of recommendations for CML management from 2006 and 2009.<\/p>\n
    Key words<\/strong>: chronic myeloid leukemia, tyrosine kinase inhibitors, evaluation of treatment response<\/p>\n","casopis":[{"ID":995,"post_author":"7","post_date":"2016-11-16 12:14:30","post_date_gmt":"2016-11-16 11:14:30","post_content":"
    Biochemistry <\/strong><\/h4>\r\n
      \r\n \t
    • Biochemical inflammation markers<\/li>\r\n \t
    • Biochemical examinations in liver diseases<\/li>\r\n \t
    • Biochemical diagnosis in diseases of GIT<\/li>\r\n \t
    • Hypoglycemia<\/li>\r\n \t
    • Urolithiasis as a result of metabolic diseases<\/li>\r\n \t
    • Indication and application of tumor markers in clinical practice<\/li>\r\n \t
    • Monoclonal gammopathies \u2013 laboratory examinations in diagnosis and monitoring<\/li>\r\n \t
    • Hormones in diagnosis of reproductive function disorders<\/li>\r\n \t
    • Cerebrospinal fluid diagnosis of diseases affecting the nervous system<\/li>\r\n \t
    • Determining trace elements in blood serum<\/li>\r\n<\/ul>\r\n
      Genetics<\/strong><\/h4>\r\n
        \r\n \t
      • Assessing the therapeutic response in patients with chronic myelocyte leukemia treated with tyrosine kinase inhibitors<\/li>\r\n \t
      • Hormones in diagnosis of reproductive functions\u2019 disorders<\/li>\r\n<\/ul>\r\n
        Hematology <\/strong><\/h4>\r\n
          \r\n \t
        • Anemias \u2013 laboratory diagnosis of the most frequently prevalent types of anemia<\/li>\r\n \t
        • Laboratory and hematological technical equipment<\/li>\r\n<\/ul>\r\n
          Immunology <\/strong><\/h4>\r\n
            \r\n \t
          • Paraneoplastic neurological syndromes and in vitro diagnosis of onconeural antibodies<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab","to_ping":"","pinged":"","post_modified":"2017-08-16 21:40:20","post_modified_gmt":"2017-08-16 19:40:20","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"30","upload_clanok":{"ID":1091,"id":1091,"title":"eckertova_hodnotenie_odpovede_na_liecbu","filename":"Eckertov\u00e1_Hodnotenie_odpovede_na_lie\u010dbu.pdf","filesize":211901,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2016\/12\/Eckertov\u00e1_Hodnotenie_odpovede_na_lie\u010dbu.pdf","link":"https:\/\/www.newslab.sk\/en\/evaluation-of-therapeutic-response-in-patients-with-chronic-myeloid-leukemia-treated-with-tyrosine-kinase-inhibitors\/eckertova_hodnotenie_odpovede_na_liecbu\/","alt":"","author":"7","description":"","caption":"","name":"eckertova_hodnotenie_odpovede_na_liecbu","status":"inherit","uploaded_to":1090,"date":"2016-12-08 21:52:33","modified":"2016-12-08 21:52:33","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1090","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1090"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1090\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1090"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1090"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1090"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}