Value Of CAR-T Cell Therapy For Ph+ Acute B-cell Lymphoblastic Leukemia With T315I Mutation

Objective Philadelphia chromosome-postive acute lymphoblastic leukemia(Ph + ALL)is characterized by the presence of t(9;22)(q34;q11)genetic abnormalities and forms a BCR-ABL fusion gene.Leukemia subtype with extremely poor prognosis.The emergence of tyrosine kinase inhibitors(TKI)has significantly improved its induction response rate,but mutations in the ABL kinase region often cause resistance to TKI during treatment,and then disease progression occurs.Among them,T315 I mutation-induced resistance is the most difficult to overcome and has been widely concerned.Because the first and second generations of TKI targeted therapy and combined chemotherapy have no obvious effect on ALL with T315 I mutation,the risk of forced transplantation is high and the survival rate is low.Therefore,new and more effective treatments are needed.Chimeric Antigen Receptor T-Cell(CAR-T)therapy,as a new immunotherapy,has achieved encouraging results in the treatment of relapsed /refractory acute B lymphocytic leukemia in recent years..This topic applies CAR-T cell therapy to Ph + ALL patients with T315 I mutations.The value of CAR-T cells in treating adult Ph + ALL patients with T315 I mutations is evaluated by evaluating its efficacy and safety.Methods Four adult Ph + ALL patients with T315 I mutation were selected,peripheral blood was collected,and autologous CD19 CAR-T cells were prepared using CAR-T cell technology.The patients were pretreated according to the patient's condition before infusion;the clinical symptoms were observed before and after treatment And physical changes,and monitor patients' blood routine,inflammatory markers,cellular immune function and other indicators,and finally consult the literature to analyze andsummarize the therapeutic effect and safety of CAR-T cell therapy.Results Two patients(50%)achieved complete remission after CAR-T cell therapy,of which one patient received sequential cord blood stem cell transplantation on the 28 th day after remission,and was still in remission as of follow-up time,with a survival time of 546 days;One case relapsed within 30 days after remission,but the combination chemotherapy failed,and eventually died of severe infection.The survival time after the mutation was found was 182 days.The other two patients had extramedullary invasion,and CAR-T cells had no significant effect after treatment.Both died of severe infection.The survival time after mutation was found to be 43 days and 176 days,respectively.Four patients had grade 1 cytokine release syndrome(CRS)and 3 had grade 2 CRS after CAR-T cell therapy,all of which caused serious consequences.Conclusion CAR-T cell therapy may be an effective treatment for patients with Ph +ALL with T315 I mutation,and it is safe.For patients receiving CR after CAR-T cell therapy,bridging hematopoietic stem cell transplantation in time may benefit patients in the long term.