Daraasad ku saabsan soo-jiidhiyaha antigen-ka T-lymphocytes (CAR-T) ee daaweynta soo noqoshada iyo dib-u-celinta non-Hodgkin lymphoma

Faahfaahin faahfaahsan:

Tani waa hal xarun, cudud keliya, daraasad summada furan. Ka dib marka la buuxiyo shuruudaha u-qalmitaanka iyo diiwaangelinta tijaabada, bukaanada ayaa mari doona leukapheresis si loo ururiyo lymphocytes autologous. Marka unugyada la soo saaro, bukaanadu waxay markaa u sii gudbi doonaan lymphodepleting chemotherapy oo leh cyclophosphamide iyo fludarabine 1-2 maalmood oo isku xigta oo ay ku xigto faleebo CAR T-unugyada qiyaasta bartilmaameedka ee 3-10 × 105 unug / kg.

Shuruudaha

Shuruudaha ka mid noqoshada:

1. CD19-positive qanjirada unugyada 'Hodgkin' waxaa xaqiijiyay cytology ama histology marka loo eego shuruudaha WHO2016:
   1. Kala firdhi lymphoma-ka weyn ee B-unugga: oo ay ku jiraan aan la cayimin (DLBCL, NOS), barar dabadheeraad ah oo la xiriira DLBCL, DLBCL maqaarka aasaasiga ah (nooca lugta), EBV-positive DLBCL (NOS); iyo lymfoma B-cell-sare (oo ay ku jiraan heerka sare ee lymphoma B-cell, NOS, iyo heerka sare ee B-cell lymphoma oo leh MYC iyo BCL2 iyo/ama BCL6); iyo dhexdhexaadiyaha aasaasiga ah ee weyn ee B-cell lymphoma; iyo histiocytosis B-cell lymfoma oo qani ku ah T-unugyada; oo beddeshay DLBCL (sida lymphoma follicular, leukemia lymphocytic chronic/lymphocytic B-lymphocytic lymphoma oo beddelay DLBCL); bukaanka qaba kuwa kor ku xusan buro noocyada ayaa lagu daweeyay ugu yaraan daawooyinka safka koowaad iyo labaad waxayna qabaan cudur deggan ≤12 bilood, ama marka cudurka ugu wanaagsan uu horumaro ka dib waxtarka; ama horumarka cudurka ama soo noqoshada ka dib tallaalka unugyada asliga ah ee iswada leh ≤12 bilood;
   2. Marka loo eego shuruudaha WHO2016 cytology ama histology ayaa xaqiijiyay CD19 togan: unugga follicular qanjiro. Bukaanka qaba nooca buro waxa ay heleen ugu yaraan daawaynta safka saddexaad, iyo soo noqoshada ama horumarka cudurku waxa uu dhacay 2 sano gudahood ka dib daawaynta safka saddexaad ama ka badan. Hadda ku jira horumarka cudurka, cudur deggan, ama cafis qayb ah;
   3. Sida laga soo xigtay WHO2016 heerka cytology ama histology ayaa xaqiijiyay CD19 togan: lymphoma unugga mantle. Bukaannada noocan oo kale ah lama bogsiin ama dib u soo noqon ka dib ugu yaraan daweyn saddex-line ah oo kuma habboona beddelidda unugyada tarma ama dib u soo noqoshada ka dib tallaalka unugyada tarma;
2. Da'da ≥18 sano jir (oo ay ku jirto xadka);
3. Marka loo eego nooca 2014 ee shuruudaha Lugano, waxaa jira ugu yaraan hal nabar laba-cabbir ah oo la cabbiri karo sida saldhigga qiimeynta: dhaawacyada intranodal, waxaa lagu qeexay sida: dhexroor dheer>1.5cm; dhaawacyada ka baxsan, dhexroorka dheer waa in uu ahaado>1.0cm;
4. Kooxda Iskaashatada Bariga ee Oncology heerka waxqabadka kooxda dhibcaha ECOG 0-2;
5. Helitaanka xididka ee looga baahan yahay ururinta waa la dhisi karaa, waxaana jira unugyo ku filan oo ay soo ururiyeen apheresis aan dhaqdhaqaaq lahayn oo loogu talagalay soo saarista unugyada CAR-T;
6. Shaqada beerka iyo kelyaha, shaqada wadnaha sambabada waxay buuxisaa shuruudaha soo socda:
   • Serum creatinine≤2.0×ULN;
   • Jajabka ka bixista ventricular ee bidix ≥ 50% mana jiro dhiigbax cad oo wadnaha ah, ma jiro ECG aan caadi ahayn;
   • Dheefta oksijiinta dhiigga ≥92% xaalad aan oksijiin ahayn;
   • Wadarta guud ee bilirubin≤2.0×ULN (marka laga reebo muhiimad caafimaad la'aan);
   • ALT iyo AST≤3.0×ULN (oo leh burada beerka oo la soo galiyay≤5.0×ULN);
7. Inuu awoodo inuu fahmo oo si ikhtiyaari ah u saxeexo oggolaanshaha la wargeliyey.

Shuruudaha Ka-saarista:

1. La helay daawaynta CAR-T ama daaweynta unugyada kale ee hiddo-sidaha wax laga beddelay ka hor baaritaanka;
2. La helay daawaynta ka hortagga burooyinka (marka laga reebo xakamaynta isbaarada difaaca habdhiska ama daawaynta kicinta) 2 todobaad gudahood ama 5 nolosha badhkeed ( midkasta oo ka gaaban) kahor baaritaanka. 3 nolosha nuska ah ayaa looga baahan yahay inay isdiiwaangeliyaan (tusaale, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonist receptor, 4-1BB agonist, iwm.);
3. Kuwa hematopoietic stem cell transplantation (ASCT) gudahood 12 todobaad ka hor apheresis, ama kuwaas oo hore u helay allogeneic hematopoietic stem cell transplantation (HSCT), ama kuwa leh xubin adag oo tallaalka; xakamaynta difaaca jirka ayaa loo baahan yahay 2 todobaad gudahood ka hor inta aan la joojinin Fasalka 2 iyo wixii ka sareeya GVHD ee daawada;
4. Bukaanka qaba ku lug lahaanshaha atrial ama ventricular lymphoma ama waxay u baahan yihiin daaweyn degdeg ah sababtoo ah tirada burooyinka sida xannibaadda mindhicirka ama cadaadiska xididdada;
5. Lagu tallaalay tallaal nool oo la dhimay 6 toddobaad gudahood ka hor inta aan la nadiifin baraska;
6. Shilalka cerebrovascular ama suuxdin ayaa dhacay 6 bilood gudahood ka hor inta aan la saxiixin ICF;
7. Taariikhda Wadnaha Wadnaha, Wadnaha Wadnaha ama stent, angina aan degganeyn ama cudur kale oo caafimaad oo muhiim ah 12 bilood gudahood ka hor inta aan la saxiixin ICF;
8. Cudurada difaaca jirka ee firfircoon ama aan la xakameynin (sida cudurka Crohn, rheumatoid arthritis, lupus erythematosus systemic), marka laga reebo kuwa aan u baahnayn daaweyn nidaamsan;
9. Burooyinka malignantiga ah ee aan ahayn lymphoma non-Hodgkin 5 sano gudahood ka hor baaritaanka, marka laga reebo kansarka ilmagaleenka si ku filan oo loo daaweeyay oo ku yaal goobta, unugyada basal ama kansarka maqaarka unugyada squamous, kansarka qanjirka 'prostate' ka dib dib-u-soo-celinta xagjirka ah, Kansarka dhuuntaoma in situ;
10. Caabuqa aan la xakameyn karin 1 toddobaad gudahood ka hor baaritaanka;
11. Hepatitis B surface antigen (HBsAg) ama cagaarshowga B core antibody (HBcAb) fayraska cagaarshow B ee togan iyo kan durugsan ee dhiiga (HBV) ogaanshaha titer DNA wuu ka weyn yahay qiyaasta tixraaca caadiga ah; ama fayraska cagaarshow C (HCV) antibody togan iyo dhiigga ku hareeraysan C Fayraska cagaarshow (HCV) RNA titer titer ayaa ka weyn tirada tixraaca caadiga ah; ama fayraska difaaca jirka bini'aadamka (HIV) antibody positive; ama isfiilitada laga baaro togan; cytomegalovirus (CMV) ayaa laga helay DNA;
12. Haweenka uurka leh ama naaska nuujinaya; ama dumarka da'da dhalmada leh ee laga helay baadhis uur togan inta lagu jiro xilliga baadhista; ama bukaanada lab ama dheddig ee aan doonayn inay isticmaalaan ka-hortagga uur-qaadista laga bilaabo wakhtiga saxeexa foomka oggolaanshaha la wargeliyay ilaa 1 sano ka dib marka la siiyo faleebo unugga CAR-T;
13. Baarayaal kale ayaa u arka in aysan habooneyn in laga qeyb qaato daraasadda.