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  • 1 Semmelweis Egyetem, Általános Orvostudományi Kar, Budapest, Tűzoltó utca 7–9., 1094
  • 2 Semmelweis Egyetem, Általános Orvostudományi Kar, Budapest

Absztrakt:

Az utóbbi néhány évtized klinikai előrelépéseinek köszönhetően az akut lymphoblastos leukaemiás (ALL-) gyermekek nagy hányada ma az első vonalbeli kemoterápiás protokollok révén meggyógyul, és küzd a kortársak közé való visszatérés problémáival. Azonban a betegek jelentős részénél súlyos akut és késői terápiás mellékhatásokkal kell számolni. Emellett egyes betegcsoportok (például MLL-átrendeződéssel, hipodiploiditással, IKZF1-mutációval vagy korai prekurzor T-sejtes fenotípussal jellemezhető betegek) túlélése messze elmarad az átlagostól. Számukra nyújtanak jobb klinikai kilátásokat az újabb betegellátási stratégiák: komplex géndiagnosztika, molekulárisan célzott daganatgátlás, immunonkológia és sejtterápia. Harminc feletti azon géneknek a száma, amelyek eltéréseit azonosították leukaemiás lymphoblastokban, és patobiológiai szerepük is valamennyire ismert. Ismerünk olyan betegcsoportot is (Philadelphia-like B-sejtes ALL), ahol a génexpressziós profilalkotás ad alapot a tirozin-kináz-inhibitorok használatának. A leukaemiaasszociált immunfenotípus diagnóziskori áramlási citometriás meghatározásával és genetikai módszerekkel követhetővé vált a minimális residualis betegség. A blastfelszíni differenciációs klaszterek (elsősorban CD19, CD20 és CD22 a malignus B-sejteken) epitópjai monoklonális antitestekkel támadhatók. Fokozható a tumorellenes immunitás is, részben szintén a tumor sejtfelszíni markereinek (bispecifikus T-sejt-kapcsolóknál, kiméra antigénreceptorú T-sejtes terápiánál), részben pedig a tumorspecifikus immunsejteknek (immunellenőrzőpont-gátlóknál) a kihasználása révén. A jelen közleményben áttekintést kívánunk adni a patogenetika új irányairól, a betegségkövetés modern módjairól és a célzott citotoxicitás innovatív lehetőségeiről biztató klinikai tanulmányok alapján. Orv Hetil. 2018; 159(20): 786–797.

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