Kodi Therapy Target ndiyabwino kuposa Chemotherapy ya Relapsed FLT3-Mutated Acute Myeloid Leukemia?

Mfundo

Mu AML yobwereranso komanso yosavuta yopulumuka zaka 5 zokha zokha, 25%, kafukufuku wamankhwala poyerekeza ndi chithandizo chamankhwala ndi salvage cytotoxic chemotherapy adawonetsa chithandizo chothandizidwa kutengera mtundu wa ma genomic ndi ma molekyulu atha kukhala ndi zotsatira zabwino ndikucheperachepera kwa zochitika zoyipa, poyerekeza ndi chemotherapy.

Acute Myeloid Leukemi(AML) ndi a khansa a magazi ndi m`mafupa m`maselo ndipo makamaka amakhudza akuluakulu. AML imadziwika ndi kukula kosalamulirika komanso kochulukira kwa magazi osakhwima omwe amapanga maselo a myeloblast m'mafupa omwe amathamangitsa maselo abwinobwino amagazi. Cholinga cha chithandizo cha AML ndikuchotsa maselo onse osadziwika a leukemia ndikupangitsa kuti wodwalayo akhululukidwe. Komabe, nthawi zambiri, ngati maselo onse a khansa ya m'magazi sanafafanizidwe ndi chithandizo, matendawa amatha kubwereranso pambuyo pokhululukidwa kwakanthawi. Odwala ena, khansa ya m'magazi imatsutsana ndi chithandizo chamankhwala a chemotherapy ndipo amaonedwa kuti ndi osagwirizana.

Zomwe zili bwino - Therapy Target kapena Chemotherapy?

Pankhani ya AML yobwereranso kapena yosiyanitsidwa, kusanthula kwamtundu wa chotupa kumapereka chidziwitso chochulukirapo pamikhalidwe ya mamolekyulu omwe amayambitsa khansa amene angathe kuthandizidwa ndi machiritso omwe akulunjika kwambiri. Chimodzi mwazovuta zamtundu wotere zomwe zimapezeka mu 30% ya odwala AML ndi FMS-monga tyrosine kinase 3 (FLT3) receptor, ngati ilipo, ndi dalaivala wa matenda komanso chifukwa chokana mankhwala a chemotherapy.Papaemmanuil E et al, Watsopano Engl. J Med., 2016). Pali mitundu iwiri yayikulu ya zovuta za mtundu wa FLT2 zomwe zapezeka mu ma genome a AML: kubwereza tandem ya FLT3 gene (ITD) kapena kusintha kwa gawo la tyrosine kinase la mtundu wa FLT3 (TKD). Zonsezi zimapangitsa kuti njira yovomerezeka ya FLT3 yolandirira yomwe imathandizira kukula kwa khansa ya m'magazi ndikuipangitsa kuti isagwirizane ndi njira zamankhwala zamankhwala. Bokosi lazida zamankhwala omwe akulimbana nawo omwe ali ndi kusankha kosiyanasiyana, potency ndi zochitika zamankhwala, zomwe zavomerezedwa kapena kukupangidwira kwa FLT3 mutated AML ndi:

• Malo osambira, mankhwala osokoneza bongo, amavomerezedwa pamodzi ndi 7 + 3 (cytarabine + daunorubicin) chemotherapy kwa odwala omwe amapezeka kuti ali ndi AML ndi kusintha kwa FLT3. Koma kwa odwala omwe abwerera mobwerezabwereza kapena osokoneza bongo a AML, midostaurin sinawonetse chithandizo chamankhwala chosatha ngati wothandizira m'modzi. (Mwala RM et al, New Engl. J Med., 2017; Fisher T, et al, J Clin Oncol., 2010)
• Sorafenib, mankhwala ena owunikira ambiri, awonetsa zochitika zamankhwala kwa odwala omwe ali ndi FLT3-mutated AML. (Borthakur G, et al, Haematologica, 2011)
• Quizartinib, kalasi yatsopano ya FLT3 inhibitor idawonetsa zochitika m'modzi mwa odwala omwe abwerera m'mbuyo komanso osintha omwe ali ndi FLT3-ITD koma kuyankhako kunali kwakanthawi kochepa chifukwa chosayang'ana kusintha kwa FLT3 TKD komwe kumatha kuchitika panthawi yachipatala. (Cortes JE Et al, Lancet Oncol., 2019)
• Gilteritinib ndi gulu lina latsopano la mankhwala pakukula kwamankhwala, lomwe limasankha kusintha kwa ITD ndi TKD. Mu gawo lachiwiri la kafukufuku wamankhwala, 1% ya odwala omwe abwerera m'mbuyo komanso osamvera AML adakhululukidwa kwathunthu. (Perl AE, et al, Lancet Oncol., 2017)

Gawo lachitatu lakuyesa kwamankhwala poyerekeza ndi zomwe zimathandizidwa ndi Gilteritinib vs.savage chemotherapy mu odwala a 3 omwe abwereranso m'mbuyo komanso osokoneza bongo (Trial No. NCT371). Mwa odwala 02421939 omwe abwereranso komanso obwerera m'mbuyo a AML, 371 adapatsidwa mwayi wopita ku gulu la Gilteritinib ndi 247 ku gulu la chemotherapy. Chiwerengero cha kubwereranso komanso kutsutsa m'magulu onsewa chinali pafupifupi 124: 60. Njira zopulumutsira chemotherapy zinali zamphamvu kwambiri: Mitoxantrone, Etoposide, Cytarabine (MEC), kapena Fludarabine, Cytarabine, Granulocyte colony-stimulating factor and Idarubicin (FLAG-IDA); kapena njira zochepa zochiritsira: Cytarabine wochepa, kapena Azacitidine. Zotsatira zomwe zatulutsidwa posachedwa za mayeserowa zidawonetsa kuti gulu lomwe likulimbana ndi Gilteritinib lidapulumuka miyezi 40 poyerekeza ndi miyezi 9.3 ndi gulu la chemotherapy la salvage. Panali odwala 5.6% omwe adakwanitsa kukhululukidwa kwathunthu ndikuchira pang'ono kapena kwathunthu kwa hematologic mu gulu la Gilteritinib, pomwe 34% yokha anali mgulu la chemotherapy. Komanso, zovuta zoyipa kwambiri zaku grade 15.3 kapena kupitilira apo zimapezeka kuti zimachitika kawirikawiri pagulu lolimbana ndi gulu la chemotherapy (Perl AE, et al. Watsopano Engl. J Med., 2019).

Zomwe tazitchulazi zithandizira kuti pakuvutikaku kuchiza AML yobwereranso komanso yotsutsa omwe ali ndi vuto lakuchepa komanso kupulumuka kwa zaka 5 zokha 25%, chithandizo chofunikira chokhazikitsidwa ndi ma genomic ndi ma molekyulu chitha kukhala ndi zotulukapo zabwino ndikucheperachepera kwa zochitika zoyipa, poyerekeza ndikupitilira mankhwala a chemotherapy.

Chakudya chomwe mumadya komanso chomwe chimakupatsani thanzi ndi chisankho chomwe mumapanga. Lingaliro lanu liyenera kuphatikizapo kulingalira za kusintha kwa majini a khansa, khansa, chithandizo chamankhwala chopitilira muyeso, zovuta zilizonse, zidziwitso za moyo, kulemera, kutalika ndi zizolowezi.

Kukonzekera kwa khansa kuchokera ku addon sikudalira pakusaka kwa intaneti. Zimakusankhirani zomwe mungasankhe malinga ndi sayansi yamayendedwe omwe asayansi athu ndi akatswiri a mapulogalamu. Mosasamala kanthu kuti mumasamala kumvetsetsa zomwe zimayambira zamagulu am'thupi kapena ayi - pakukonzekera zakudya za khansa kumvetsetsa kumafunikira.

Yambirani TSOPANO ndikukonzekera zakudya zanu poyankha mafunso okhudzana ndi khansa, kusintha kwa majini, mankhwala opitilira muyeso ndi zowonjezera, chifuwa chilichonse, zizolowezi, moyo, gulu la zaka komanso jenda.

Odwala khansa nthawi zambiri amakhala ndi zovuta zosiyanasiyana chemotherapy mavuto zomwe zimakhudza moyo wawo ndikuyang'ana njira zina zochiritsira khansa. Kutenga chakudya choyenera ndi zowonjezera zowonjezera kutengera zomwe asayansi amalingalira (kupewa kulosera ndi kusankha mwachisawawa) ndiye njira yabwino kwambiri yachilengedwe khansa ndi zotsatira zake zokhudzana ndi chithandizo.

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