O Targeted Therapy e sili atu nai lo Chemotherapy mo Toe Faʻafitauli FLT3-Mutated Acute Myeloid Leukemia?

faatumutumuga

I le toe faʻaleleia ma le toe ola AML ma le le lelei 5 tausaga ola o naʻo le 25%, o se suʻesuʻega suʻesuʻega faʻatusatusaina faʻatulagaina togafitiga ma salvage cytotoxic chemotherapy faʻaalia togafitiga faʻavae faʻavaeina i luga ole genomic ma molemole faʻamaumauga e mafai ona sili atu taunuʻuga ma maualalo taimi masani o mea leaga, pe a faʻatusatusa i chemotherapy.

Leukemi Mieloid Mata'utiaa (AML) o le a kanesa o le toto ma le ponaivi sela ma e masani ona afaina ai tagata matutua. O le AML o loʻo faʻaalia i le le pulea ma le tele o le tuputupu aʻe o le toto le matua e fausia ai sela myeloblast i le gaʻo ponaivi e faʻaumatia ai sela masani. O le sini o togafitiga AML o le faʻaumatia uma o sela leukemia e le masani ai ma faʻamagalo le gasegase. Peita'i, i le tele o tulaga, afai e le'i soloiesea uma sela leukemia i le togafitiga, e mafai ona toe fo'i le ma'i pe a uma ona fa'amagaloga mo sina taimi. I nisi o gasegase, o le lukimia e tete'e i le tulaga o togafitiga o le chemotherapy ma e manatu e le mafai.

O le fea e sili atu - Targeted Therapy poo Chemotherapy?

I tulaga o le toe fa'afo'i po'o le fa'alavelaveina o le AML, o le fa'avasegaina o genomic o le tuma e maua ai le tele o fa'amatalaga i uiga mole o lo'o fa'avaeina. kanesa ona mafai lea ona togafitia i togafitiga e sili atu ona taulai. O se tasi o faʻalavelave faʻalavelave faʻafuaseʻi o loʻo maua i le 30% o tagata maʻi AML o le FMS-pei o le tyrosine kinase 3 (FLT3), pe a iai, o se avetaʻavale faʻamaʻi ma mafua ai le tetee i le chemotherapy (Papaemmanuil E et al, New Engl. J Med., 2016). E i ai ituaiga autu e 2 o FLT3 genomic faʻaletonu ua maua i AML genome: o se faʻalua faʻaluaina o le FLT3 gene (ITD) poʻo ni suiga i le tyrosine kinase vaega o le FLT3 gene (TKD). O faʻavasegaga uma e lua na mafua ai le soʻona faʻagaeʻetia o le FLT3 receptor signaling pathway e faʻatosina le le taofiofia o le tuputupu aʻe o le lukimia ma mafai ai ona teteʻe atu i le tulaga masani o le tausiga chemotherapy filifiliga. O le mea faigaluega o fualaʻau faʻatulagaina ma eseese fesuiaʻiga, gafatia ma falemaʻi gaioiga, na faʻamaonia pe i le atinaʻe mo FLT3 faʻafouina AML o:

• Midostaurin, o se vailaʻau tele faʻatulagaina, ua faʻamaonia faʻatasi ma le tulaga masani 7 + 3 (cytarabine + daunorubicin) chemotherapy mo tagata mamaʻi na faʻatoa maua faʻamaonia ma AML ma FLT3 suiga. Ae mo tagata mamaʻi e iai le AML ua toe faʻafou, e leʻi faʻaalia e le midostaurin se faʻamanuiaga tumau ile avea o se sui e toʻatasi. (Stone RM et al, New Engl. J Med., 2017; Fisher T, et al, J Clin Oncol., 2010)
• Sorafenib, le isi tele-kinase faʻatatau fualaʻau, na faʻaalia togafitiga togafitiga i tagata mamaʻi ma FLT3-mutated AML. (Borthakur G, et al, Haematologica, 2011)
• Quizartinib, o se vasega fou o le poloka FLT3 taofi na faʻaalia ai le tasi-soʻotaga gaioiga gaioiga ma toe feololo maʻi ma FLT3-ITD ae o le tali na puʻupuʻu ona o le le faʻamoemoeina FLT3 TKD suiga e mafai ona tulaʻi mai i taimi o togafitiga. (Cortes JE et al, Lancet Oncol., 2019)
• Gilteritinib o se isi vasega fou o vailaʻau i le falemaʻi atinaʻe, e filifilia mo uma ITD ma TKD suiga. I le vaega 1-2 falemaʻi suʻesuʻe, 41% o tagata mamaʻi na toe faʻafouina ma toe faʻaola AML na i ai se faʻamagaloga atoa. (Perl AE, ma isi, Lancet Oncol., 2017)

O le laʻasaga 3 faʻataʻitaʻi faʻataʻitaʻi faʻataʻitaʻi le faʻafitauli o le togafitiga faʻasolosolo Gilteritinib vs. salvage chemotherapy i le 371 na toe faʻafouina ma toe faʻaola AML tagata mamaʻi (Trial Nu. NCT02421939). Mai le toʻatele o tagata mamaʻi a le AML ua toe 371, o 247 na tofia faʻasolosolo i le vaega a Gilteritinib ma le 124 i le vaega faʻaola o le chemotherapy. O le fuataga o le toe faʻafouina ma faʻafefeteina i vaega uma e lua e lata ile 60:40. O togafitiga o le chemotherapy o le salvage o le maualuga o togafitiga: Mitoxantrone, Etoposide, Cytarabine (MEC), poʻo Fludarabine, Cytarabine, Granulocyte colony-stimulate factor ma Idarubicin (FLAG-IDA); pe maualalo le malosi togafitiga filifiliga: maualalo-fualaʻau Cytarabine, poʻo Azacitidine. Talu ai nei na faʻasalalau faʻaiuga o lenei faʻamasinoga na faʻaalia ai o le vaega faʻapitoa mo togafitiga ma Gilteritinib na i ai le saoasaoa o le 9.3 masina pe a faʻatusatusa i le 5.6 masina ma le salvage chemotherapy kulupu. E i ai 34% tagata mamaʻi na mauaina le faʻamagaloina atoatoa ma se vaega poʻo le maeʻa o le hematologic toe faʻaleleia i le vaega a Gilteritinib, ae naʻo le 15.3% i le vaega o le chemotherapy. Faʻapea foi, ogaoga mea leaga na tutupu o le vasega 3 pe maualuga atu na maua e tupu laʻititi i le faʻatulagaina vaega i luga o le chemotherapy kulupu (Perl AE, et al, New Engl. J Med., 2019).

O faʻamatalaga o loʻo i luga e lagolagoina ai, i lenei faigata e togafitia ai le toe faʻafouina ma le toe ola o le AML, ma le le lelei o le vavalo ma le 5 tausaga e ola ai naʻo le 25%, o togafitiga faʻatulagaina e faʻavae i luga o le genomic ma le molamilo faʻamaumauga e mafai ona sili atu lona taunuʻuga ma le maualalo o taimi o faʻalavelave tutupu, pe a faʻatusatusa i le faʻaauau togafitiga o chemotherapy.

O a meaʻai e te 'ai ma poʻo fea mea faʻaopopo e te aveina o se filifiliga e te faia. Lau filifiliga e tatau ona aofia ai le iloiloina o le kanesa gafa fesuiaʻiga, o le kanesa, faifai pea togafitiga ma faʻaopopoga, soʻo se allies, olaga faʻamatalaga, mamafa, maualuga ma masani.

O le fuafuaina meaʻai mo kanesa mai le addon e le faʻavae luga o initaneti sailiga. E otometi lava le faia o faʻaiuga mo oe faʻavae i luga o molemole faʻasaienisi faʻatinoina e o tatou saienitisi ma inisinia polokalama. Tusa lava pe e te popole e malamalama i le faʻavaeina o meaola niniʻi o le biochemical pe leai - mo le fuafuaina o meaʻai mo le kanesa e manaʻomia le malamalama.

Amata NEI i lau taumafataga fuafuaina e ala i le taliina o fesili i le igoa o le kanesa, fesuiaʻiga o gafa, togafitiga faifai pea ma supa, soʻo se allergy, masani, ituaiga olaga, tausaga kulupu ma itupa.

Kanesa gasegase masani ona feagai ma le eseʻese aafiaga o le chemotherapy lea e afaina ai lo latou tulaga lelei o le olaga ma vaavaai mo isi togafitiga mo kanesa. Aveina o le saʻo meaʻai ma mea faʻaopopo e faʻavae i mafaufauga faasaienitisi (aloese mai taumatematega ma filifiliga fa'afuase'i) ole fofo fa'anatura sili lea mo kanesa ma a'afiaga e fa'atatau i togafitiga.

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