Impumelelo Kwezemfundo | Iqela Lezonyango laseLu Daopei Lipapasha Uphando Lweklinikhi Olumangalisayo kwiBritish Journal of Haematology

Kwimpumelelo ebalulekileyo yeQela lezonyango laseLu Daopei, iphepha lophando lweklinikhi eliphambili elinesihloko esithi "Uphononongo olukhuselekileyo nolusebenzayo lwe-allogeneic haematopoietic stem cell transplantation kwizigulane ze-T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma eziphinde zabuyela kwimeko yazo yangaphambili ezifumene uxolelo olupheleleyo emva konyango lwe-T-cell T-cell oluvela kwi-autologous CD7 chimeric antigen receptor" ipapashwe kwincwadi edumileyo ethi Ijenali yaseBritane yeHaematology (IF=5.1). Olu phononongo, olubhalwe nguGqr. Cao Xingyu kunye noNjingalwazi uLu Peihua njengombhali ohambelanayo, lugxile kumandla athembisayo okuhlanganisa i-allo-HSCT kwizigulane ze-R/R T-ALL kunye ne-T-LBL ezifumene i-complete remission (CR) emva konyango lwe-autologous CD7 CAR-T.

Imvelaphi yoPhando:

Iintsholongwane ze-T-cell, ezifana ne-T-ALL kunye ne-T-LBL, zaziwa ngokuba nolaka kunye nokunganyangeki kakhulu kunyango. Kwizigulane ezine-T-ALL/LBL (R/R T-ALL/T-LBL) enganyangekiyo okanye eziphinde zabuyela kwi-T-ALL/LBL (R/R T-ALL/T-LBL), unyango lwendabuko lunika impumelelo encinci kunye neengxelo ezimbi. Nangona kunjalo, unyango lwe-CD7 CAR-T luvele njengempumelelo enokubakho, lubonisa ithemba elikhulu ekunyangeni ezi meko zinzima ukunyanga, nangona zisekwinqanaba lokuqala lovavanyo lweklinikhi. Xa kulandelwa kukuhlanganiswa ne-allo-HSCT, izigulane ezifikelela kwi-CR ngonyango lwe-CD7 CAR-T zinikwa ithuba lokwenene lokufumana uxolelo lwexesha elide.

Indlela yokufunda:

Olu phononongo olujonga emva luhlalutye izigulane ze-R/R T-ALL kunye ne-T-LBL ezafumana unyango lwe-NS7 CAR-T, kulandele ukuhlanganiswa kwe-allo-HSCT phakathi kukaNovemba 2020 noJanuwari 2023 kwiSibhedlele iLu Daopei. Olu phononongo luhlolisise izinto ezahlukeneyo, kubandakanya ubudala besigulana, inombolo yekopi yeseli ye-CAR-T ngaphambi kokufakelwa, kunye neendlela ezahlukeneyo zokulinganisa i-CAR-T, ukuvavanya impembelelo yazo kwiziphumo zokufakelwa. Iziphumo zithelekiswe nezo zezigulane ezili-124 ezifumene i-CR nge-chemotherapy kulandele i-allo-HSCT.

Iziphumo eziphambili:

Olu phononongo luquke izigulane ezingama-34 ze-R/R T-ALL/T-LBL ezifumene i-CR emva konyango lwe-NS7 CAR-T zaza emva koko zafumana i-allo-HSCT. Ixesha eliphakathi phakathi konyango lwe-CAR-T kunye nokufakelwa isilwanyana yayiziintsuku ezingama-57.5. Okuphawulekayo kukuba, ama-47.1% ezigulana zazinesifo sokungavumi ukuphinda zifumane unyango, ngelixa ama-52.9% ayenesifo esiphinde sabuyela kwisifo. Emva kokufakwa kwe-CAR-T, i-cytokine release syndrome (CRS) yenzeka kwizigulane ezingama-33, apho ama-94.1% ayene-CRS yeBanga loku-1 ukuya kwelesi-2. Ngethamsanqa, akukho zigulana zifumene i-immune effector cell-associated neurotoxicity syndrome (ICANS).

Kwiintsuku ezingama-28 emva kwe-CAR-T, izigulana ezingama-31 zifumene i-MRD-negative CR, ngelixa izigulana ezi-3 zine-MRD-positive CR. Olu phononongo lukwafumanise ukuba izigulana ezine-≤20% ye-bone marrow blasts ngaphambi kokufakelwa zazinezinga lokubuyela umva le-0% kwiinyanga ezili-18 emva kokufakelwa. Xa kuthelekiswa nezigulana ze-CR ezisekelwe kwi-chemotherapy, amazinga okusinda (OS) eminyaka emi-2 ayefana: 61.9% kwiqela le-CD7 CAR-T vs. 67.6% kwiqela le-chemotherapy. Ukongeza, amazinga okusinda ngaphandle kwe-leukemia (LFS) yeminyaka emi-2 ayephantse afana (62.3% vs. 62.0%).

Okubalulekileyo kukuba, izigulane ezineminyaka eyi-≤14 ubudala ezafumana unyango lwe-CD7 CAR-T zazine-87.5% OS kunye ne-LFS yeminyaka emi-2 ebalaseleyo. Iziphumo zibonisa ukuba unyango lwe-CD7 CAR-T olulandelwa yi-allo-HSCT lunokubonelela ngenye indlela ekhuselekileyo nesebenzayo kwizigulane ze-R/R T-ALL/T-LBL ezingafanelekiyo kunyango lwendabuko.

Isiphelo:

Olu phononongo lugqiba kwelokuba indibaniselwano yonyango lwe-CD7 CAR-T elandelwa yi-allo-HSCT inika indlela yonyango ethembisayo nesebenzayo kwizigulane ze-R/R T-ALL/T-LBL. Iziphumo bezifana nezo zifunyenwe nge-chemotherapy kunye ne-allo-HSCT, kungekho kwanda kokufa okungabuyeliyo, okubonelela ngokhetho lonyango oluxabisekileyo kwizigulane ezineendlela zonyango ezilinganiselweyo. Iziphumo zophando zinika ithemba lokuxolelwa ixesha elide kunye nokusinda, ingakumbi kwizigulane ezisengozini enkulu ezidibana ne-allo-HSCT ngexesha elifanelekileyo.

Impembelelo kunye neMbono yeXesha elizayo:

Ukupapashwa kolu phando luphambili kwi Ijenali yaseBritane yeHaematologybubungqina bokuzinikela kunye nobuchule beQela lezonyango laseLu Daopei. Le mpumelelo igxininisa imizamo eqhubekayo yesibhedlele ekuphuculeni unyango lweengxaki zegazi kunye negalelo labo elibalulekileyo kuluntu lwezonyango lwehlabathi. Igxininisa amandla onyango lwe-CD7 CAR-T njengokhetho olufanelekileyo kwizigulana ezine-R/R T-ALL/T-LBL kwaye ibonisa ukuzinikela kweqela ekutyhaleni imida ye-hematological. Unyango lomhlaza.