Efficacy And Safety Of CD19 CAR T Cells In The Treatment Of Relapsed And Refractory Acute B Lymphocytic Leukemia With Central Nervous System Invasion

Background and purpose: Adults with relapsed and refractory acute B-lymphoblastic leukemia(B-ALL)have a poor prognosis,and the 5-year survival rate is less than 10%.Relapsed and refractory B-ALL accompanied with central nervous system(CNS)infiltration is 1% to 15%,and the prognosis of these patients is worse.Most of these patients show multi-system infiltration,which makes early prediction and evaluation difficulty.It is urgent to find a safer and effective treatment to improve the prognosis of patients with relapsed and refractory B-ALL accompanied with CNS infiltration.In this study,we investigate the efficacy and security of CD19 CAR T cells in the treatment of relapsed and refractory B-ALL accompanied with CNS infiltration.Methods: Seven patients with relapsed and refractory B-ALL accompanied with CNS infiltration in our hospital from January 2015 to December 2018 were enrolled.Clinical data,laboratory examination results of peripheral blood,cerebrospinal fluid and bone marrow were collected.CNS status,bone marrow tumor burden,recurrence free survival and first recurrence site were analyzed to evaluate the efficacy of treatment.The occurrence of non-hematological adverse events,cytokine release syndrome(CRS),immune effector cell-related neurotoxic syndrome,and immunoglobulin decline after treatment were analyzed to evaluate the security of treatment.Results: All patients were evaluated for efficacy and security within 28 days after CD19 CAR T cells infusion.(1)The overall response rate(ORR)was 57.14%.5 patients(71.43%)reached CNS-1 status,2 patients(28.57%)reached CNS-2 status.6 patients(85.71%)achieved complete remission of bone marrow infiltration.The median of recurrence-free survival was 1 month,and the site of first recurrence was bone marrow.(2)5 patients(71.43%)occurred infection after CAR T cells infusion;5 patients(71.43%)experienced CRS(4 patients with grade 1-2 CRS,1 patient with grade 3 CRS).1 patient(14.29%)had immune effector cell-related neurotoxic syndrome.Mild treatment-related immunoglobulin decline was observed in all patients.None of the patients with adverse events had serious clinical outcomes after symptomatic treatment.Conclusion:CD19 CAR T cell therapy for patients with central nervous system invasion of relapsed and refractory acute B-lymphocytic leukemia patients with primary disease and CNSL is expected to achieve complete remission;CRS,treatment-related neurotoxicity,immunoglobulin levels and other phenomena may appear during treatment,without tumor Lysis syndrome and off-target effects,controllable adverse reactions...