ʻOi aku ka maikaʻi o ka Therapy Therapy ma mua o Chemotherapy no FLT3-Mutated Acute Myeloid Leukemia?

o ka Naauao

I loko o ka AML i hoʻi hou a me ka refactory me ke ola maikaʻi ʻole o 5 mau makahiki o 25% wale nō, ua hōʻike ʻia kahi noiʻi hoʻokolohua e hoʻohālikelike ana i ka lāʻau hoʻomākaukau me ka chemotherapy cytotoxic salvage e pili ana i ka genomic a me ka mole molekula hiki ke loaʻa nā hopena maikaʻi me ka pinepine haʻahaʻa o nā hanana maikaʻi ʻole, ke hoʻohālikelike ʻia i ka chemotherapy.

Leukemi Myeloid Acutea (AML) he a Ka maʻi 'aʻai o ke koko a me ka iwi iwi a pili nui i na kanaka makua. Hōʻike ʻia ʻo AML e ka ulu ʻole ʻana a me ka ulu nui ʻana o ke koko ʻoi ʻole e hana ana i nā pūnaewele myeloblast i loko o ka ʻiʻo o ka iwi e hoʻopiʻi i nā ʻāpana koko maʻamau. ʻO ka pahuhopu o ka mālama ʻana i ka AML, ʻo ia ka hoʻopau ʻana i nā maʻi leukemia maʻamau a loaʻa i ka mea maʻi i ke kala ʻana. Eia nō naʻe, i nā manawa he nui, inā ʻaʻole i holoi ʻia nā maʻi leukemia a pau e ka mālama ʻana, hiki ke hoʻi hou ka maʻi ma hope o ke kala ʻana no kekahi manawa. I kekahi poʻe maʻi, kūʻē ka leukemia i ke kūlana o ka mālama ʻana i ka chemotherapy a manaʻo ʻia he refractory.

ʻO ka mea ʻoi aku ka maikaʻi - Targeted Therapy a i ʻole Chemotherapy?

I nā hihia o ka AML i hoʻihoʻi ʻia a i ʻole refractory, ʻo ka genomic profiling o ka tumo e hāʻawi i nā ʻike hou aʻe i nā ʻano molekala i lalo o ka Ka maʻi 'aʻai a laila hiki ke mālama ʻia me nā lāʻau lapaʻau i manaʻo ʻia. ʻO kekahi o ia ʻano maʻi ʻino i loaʻa i loko o 30% o nā maʻi AML ʻo FMS-like tyrosine kinase 3 (FLT3) receptor, inā aia, he mea hoʻokele maʻi a kumu no ke kū'ē ʻana i ka chemotherapy (Papaemmanuil E et al, New Engl. ʻO J Med., 2016). Aia he 2 ʻano nui o FLT3 genomic abnormalities i ʻike ʻia i loko o nā genome AML: kahi kope like o ka FLT3 gene (ITD) a i ʻole nā ​​hoʻololi i ka domain tyrosine kinase o ka FLT3 gene (TKD). ʻO nā hopena ʻelua i hopena i kahi overactivation o ka FLT3 receptor signaling pathway e hoʻokele i ka ulu ʻole leollemia o ka leukemia a kūpaʻa ia i ka maʻamau o nā koho chemotherapy mālama. ʻO ka pahu hana o nā lāʻau i hoʻomākaukau ʻia me ka selectivity like ʻole, ka ikaika a me ka hana maʻi, i ʻae ʻia a i ʻole i ka hoʻomohala ʻana no FLT3 mutated AML.

• Midostaurin, kahi lāʻau i hoʻomākaukau nui ʻia, ʻae ʻia me ka chemotherapy 7 + 3 (cytarabine + daunorubicin) maʻamau no nā mea maʻi i ʻike hou ʻia me AML me FLT3 mutation. Akā no nā mea maʻi me ka AML relapsed a refactory paha, ʻaʻole i hōʻike ʻo midostaurin i kahi pōmaikaʻi lapaʻau kūmau ma ke ʻano he agena hoʻokahi. (Pōhaku RM ma, New Engl. ʻO J Med., 2017; Fisher T, et al, J Clin Oncol., 2010)
• ʻO Sorafenib, kahi lāʻau lapaʻau ʻē aʻe kinase i kuhikuhi ʻia, ua hōʻike i ka hana olakino i nā mea maʻi me AMT FLT3-mutated. (Borthakur G, et al, Haematologica, 2011)
• ʻO Quizartinib, kahi papa hou o ka mea kāpae ʻia ʻo FLT3 i hōʻike ʻia i kekahi hana a ka mea hoʻokahi i hana hou ʻia a me nā mea hōʻoluʻolu ʻole me FLT3-ITD akā ua ola pōkole ka pane ma muli o ke kau ʻole ʻana i nā hoʻololi mutt FLT3 TKD i hiki ke ala aʻe i ka wā o ka lapaʻau. (Cortes JE et al, Lancet Oncol., 2019)
• ʻO Gilteritinib kahi papa hou o ka lāʻau lapaʻau i ka hoʻomohala maʻi, i wae ʻia no nā hoʻololi ITD a me TKD ʻelua. I kahi papa 1-2 hoʻokolohua noiʻi, 41% o nā mea maʻi me ka relapsed a refactory AML i loaʻa kahi remission piha. (Perl AE, et al, Lancet Oncol., 2017)

Hoʻohālikelike kahi hoʻokolohua hoʻokolohua hoʻokolohua 3 i ka hopena o ka lāʻau hoʻomākaukau Gilteritinib vs. chemotherapy salvage i 371 mau maʻi AML i hoʻi hou ʻia (Trial No. NCT02421939). ʻO nā mea maʻi AML i hoʻi hou a hōʻoluʻolu hoʻi i ka maʻi, 371 i hāʻawi ʻino ʻia i ka hui Gilteritinib a me 247 i ka hui chemotherapy salvage. ʻO ka lakio o ka hoʻi a me ka refactory i nā hui ʻelua ma kahi o 124:60. ʻO nā koho chemotherapy salvage kekahi o nā lawelawe ʻoi loa: Mitoxantrone, Etoposide, Cytarabine (MEC), a i ʻole Fludarabine, Cytarabine, Granulositte colony-stimulate factor a me Idarubicin (FLAG-IDA); a i ʻole nā ​​koho lapaʻau hōʻemi haʻahaʻa: low-dose Cytarabine, a i ʻole Azacitidine. ʻO nā hopena i paʻi ʻia o kēia hoʻokolokolo ʻana ua hōʻike ʻia i kahi hui mālama ola me Gilteritinib i loaʻa ke ola holoʻokoʻa o 40 mau mahina ke hoʻohālikelike ʻia me nā mahina 9.3 me ka hui chemotherapy salvage. Aia he 5.6% mau maʻi i loaʻa i ke kala piha me ka hapa a i ʻole piha hematologic i ka hui Gilteritinib, ʻo 34% wale nō i ka hui chemotherapy. Eia kekahi, ua loaʻa nā hanana kūpilikiʻi koʻikoʻi o ka papa 15.3 a ʻoi aku paha i ka manawa pinepine o ka hui i kau ʻia ma luna o ka pūʻulu chemotherapy (Perl AE, et al, New Engl. ʻO J Med., 2019).

Kākoʻo ka ʻikepili ma luna i loko o kēia paʻakikī e mālama i ka AML relacted a me ka refactory me kahi wānana maikaʻi ʻole a me 5 mau makahiki o ke ola ʻana o 25% wale nō, ʻo ka hoʻomaʻamaʻa ʻia e pili ana i ka genomic a me ka mole mole e hiki ke loaʻa nā hopena maikaʻi me ka haʻahaʻa haʻahaʻa o nā hanana maikaʻi ʻole, ke hoʻohālikelike ʻia e hoʻomau lāʻau lapaʻau chemotherapy.

He aha nā meaʻai āu e ʻai ai a me nā mea hoʻopihapiha āu e lawe ai i hoʻoholo. Pono e hoʻoholo i kāu hoʻoholo ʻana e pili ana i ka hoʻololi ʻana i nā ʻāpana o ka maʻi ʻaʻai, ka maʻi ʻaʻai, nā lāʻau e hoʻomau nei a me nā mea hoʻopihapiha, nā maʻi āpau, nā ʻike nohona, ke kaupaona, ke kiʻekiʻe a me nā ʻano.

ʻAʻole hoʻokumu ʻia ka hoʻolālā meaʻai no ka maʻi ʻaʻai mai addon ma ka ʻimi pūnaewele. Hoʻokele ia i ka hoʻoholo ʻana iā ʻoe ma muli o ka ʻepekema molekole i hoʻokō ʻia e ko mākou ʻepekema a me nā ʻenekini polokalamu. Nānā ʻole inā ʻoe e noʻonoʻo e hoʻomaopopo i ke ʻano o nā ʻolaola biōmika kumu a i ʻole ʻole - no ka hoʻolālā meaʻai no ka maʻi ʻaʻai e pono ai ka ʻike.

E hoʻomaka I K NOWIA manawa me kāu hoʻolālā meaʻai e ka pane ʻana i nā nīnau e pili ana i ka inoa o ka maʻi ʻaʻai, ka hoʻololi ʻana o nā kūpuna, nā mālama ʻana a me nā mea hoʻopihapiha mau, nā maʻi āpau, nā ʻano, ka nohona, nā makahiki a me nā kāne.

ʻO nā mea maʻi maʻi maʻi e hana pinepine me nā mea ʻokoʻa nā hopena ʻaoʻao chemotherapy kahi e hoʻopili ai i ko lākou ola o ke ola a nānā i nā hoʻoponopono ʻokoʻa no ka maʻi ʻaʻai. Lawe ana i ka ka meaʻai kūpono a me nā mea hoʻopihapiha e pili ana i nā noʻonoʻo ʻepekema (ke pale aku i ka kuhi hewa a me ke koho ʻole ʻia) ʻo ia ka lāʻau kūlohelohe maikaʻi loa no Ka maʻi 'aʻai a me ka lāʻau pili i nā hopena ʻaoʻao.

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