Kuthana ndi Mavuto Anthawi Yaitali a Chithandizo cha CAR-T: Chidziwitso Chochokera ku Khansa Yachilengedwe

Chithandizo cha maselo a Chimeric Antigen Receptor (CAR)-T chasintha kwambiri chithandizo cha khansa ya m'magazi., zomwe zimapatsa chiyembekezo odwala omwe ali ndi matenda omwe safuna kuchira. Komabe, mavuto a nthawi yayitali monga matenda opatsirana ndi khansa yachiwiri akadali nkhawa yayikulu yokhudza chitetezo, malinga ndi nkhani yaposachedwa mu Khansa ya Chilengedwe.

Chithandizo cha CAR-T chinayamba kugwiritsidwa ntchito kwambiri chifukwa cha mphamvu yake yodabwitsa m'mayesero azachipatala komanso ntchito zenizeni. Ngakhale kuti poizoni woopsa monga cytokine release syndrome (CRS) ndi immune effector cell-associated neurotoxicity syndrome (ICANS) zatha kuthetsedwa ndi kupita patsogolo kwa chisamaliro chothandizira, kusanthula kwaposachedwa kukuwonetsa kufalikira kwa imfa zosabwereranso m'mbuyo (NRM) chifukwa cha matenda ndi khansa yachiwiri pakati pa omwe akuyankha ku CAR-T.

Kusanthula kwa meta komwe kumakhudza 7,604 lymphoma ndi Myeloma yambiri Odwala omwe adalandira chithandizo cha CAR-T adawonetsa kuchuluka kwa NRM konsekonse kwa 6.8%, kosiyana malinga ndi matenda osiyanasiyana komanso kapangidwe ka CAR-T.Matendawa ndi omwe amachititsa kuti anthu ambiri apezeke ndi matenda a NRM., chosagwirizana ndi Zamalonda za CAR-T kapena matenda omwe amayambitsa matendawa. Ngakhale kuti COVID-19 inakhudza kwambiri panthawi ya kafukufukuyu, matenda a bakiteriya ndi bowa aliyense anathandizira 20% ya imfa zokhudzana ndi matendawa. Ziwerengerozi zikufanana ndi zomwe zinawonedwa pambuyo pa autologous hematopoietic stem cell transplantation (auto-HSCT).

Pofuna kuchepetsa zoopsazi, ofufuza akugogomezera kugwiritsa ntchito zida zodziwira matenda monga CAR-HEMATOTOX score, yomwe imayesa zinthu monga hematopoietic reserve ndi baseline inflammation. Dongosolo lowerengerali limathandiza kuzindikira odwala omwe ali pachiwopsezo chachikulu omwe angapindule ndi maantibayotiki opangidwa kuti ateteze matenda komanso kuyang'anira chitetezo chamthupi mosamala. Chodziwika bwino n'chakuti, severe immune effect cell-associated hematotoxicity (ICAHT) imagwirizana ndi kuchuluka kwa NRM (14% poyerekeza ndi 4.5% mwa milandu yosakhala yovuta).

Matenda ena a khansa yachiwiri, kuphatikizapo matenda a myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), ndi khansa, ndi vuto lina lalikulu. Matenda a khansa amenewa makamaka amagwirizanitsidwa ndi mankhwala amphamvu monga chemotherapy ndi auto-HSCT osati mankhwala a CAR-T okha. Kutupa kwa magazi kwa Clonal, komwe kumayambitsa matenda okhudzana ndi MDS/AML, kwawonedwa mwa odwala okwana 56% asanayambe kulandira CAR-T.

Udindo wa chithandizo cha CAR-T pa khansa imeneyi ukufufuzidwabe. Ngakhale kuti milandu ya CAR-T imayambitsa khansa ikufufuzidwa. T-Cell Lymphoma Zanenedwa kuti ubale wa chifukwa chake sunatsimikizidwebe. Pa nthawi ina yodziwika bwino, kuchuluka kwa CAR-RNA kwakukulu kunapezeka mu chithandizo cha m'mimba cha T-cell lymphoma pambuyo pa CAR-T, koma kusanthula kwa majini kunachotsa kuikidwa kwa CAR ngati chifukwa chachikulu cha khansa.

Njira Zoyendetsera Zoopsa
Pofuna kupititsa patsogolo ubwino ndi chiopsezo cha chithandizo cha CAR-T, ofufuza amalimbikitsa kulowererapo koyambirira kwa odwala omwe ali ndi njira zochepa zochiritsira kale kuti achepetse poizoni wochuluka. Njira zodziwira matenda komanso kutsatira kwa nthawi yayitali kwa olandira CAR-T zitha kuwonjezera chitetezo mwa kuthandizira kuzindikira msanga ndikuwongolera zovuta.

Nkhaniyi ikugogomezera kufunika kolemba malipoti okhudza zoopsa m'mayesero azachipatala ndi m'ma registry, makamaka za matenda opatsirana, khansa yachiwiri, ndi NRM. Deta yotereyi ithandiza madokotala kukonza njira zochiritsira komanso njira zosankhira odwala.

Mapeto
Ngakhale kuti chithandizo cha CAR-T chili ndi mphamvu yochiritsira khansa ya m'magazi, kuthana ndi zoopsa zake kwa nthawi yayitali ndikofunikira kwambiri. Kafukufuku wamtsogolo ayenera kuyang'ana kwambiri pakusintha njira zodziwira matenda ndi kufufuza njira zina zothandizira odwala okalamba kapena ofooka omwe sangalolere bwino poizoni wokhudzana ndi CAR-T.

Ntchito yatsopanoyi ikukumbutsa kufunika kogwirizanitsa bwino komanso chitetezo cha mankhwala atsopano, kuonetsetsa kuti odwala padziko lonse lapansi akupeza zotsatira zabwino kwambiri.