嵌合抗原受体T细胞序贯异基因造血干细胞移植治疗Ph样急性淋巴细胞白血病21例的疗效及安全性

Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia

目的评估嵌合抗原受体T细胞(CAR-T细胞)序贯异基因造血干细胞移植(allo-HSCT)治疗Ph样急性淋巴细胞白血病(Ph样ALL)患者的疗效及安全性。方法纳入2018年3月至2023年8月在苏州大学附属第一医院接受CAR-T细胞序贯allo-HSCT治疗的21例Ph样ALL患者,对其临床资料进行回顾性分析。结果21例患者中,男14例,女7例。接受CAR-T细胞治疗时的中位年龄为22(6~50)岁。7例为ABL1样重排,14例为JAK-STAT重排。接受CAR-T细胞治疗前,12例为血液学未缓解,7例为多参数流式细胞术微小残留病(MFC-MRD)阳性,2例为MFC-MRD阴性。CAR-T细胞均来自患者自体淋巴细胞。9例接受CD19 CAR-T细胞治疗,12例接受CD19/CD22双靶点CAR-T细胞治疗。CAR-T细胞治疗后28 d评估,完全缓解率为95.2%,其中MFC-MRD阴性缓解率75.0%。19例患者出现0~2级细胞因子释放综合征(CRS),2例患者出现3级CRS,经治疗后均恢复。所有患者CAR-T细胞治疗后均接受allo-HSCT。CAR-T细胞治疗后桥接移植的中位时间为63(38~114)d。5例患者CAR-T细胞治疗后出现复发,4例为血液学复发,1例为分子学复发。ABL1组和JAK-STAT组患者的3年总生存率分别为(83.3±15.2)%和(66.6±17.2)%,3年无复发生存率分别为(50.0±20.4)%和(55.6±15.4)%,差异均无统计学意义(P值均>0.05)。结论CAR-T细胞桥接allo-HSCT,能使大部分Ph样ALL患者迅速达到深度缓解,显著延长患者的无白血病生存。

Objective To evaluate the efficacy and safety of chimeric antigen receptor T-cell(CAR-T)therapy followed by allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with Ph-like acute lymphoblastic leukemia(Ph-ALL).Methods Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included,and their clinical data were retrospectively analyzed.Results Of the 21 patients,14 were male and 7 were female.The median age at the time of CAR-T therapy was 22(6-50)years.Seven patients had ABL1-like rearrangements,and 14 had JAK-STAT rearrangements.Prior to CAR-T therapy,12 patients experienced hematologic relapse;7 were multiparameter flow cytometry minimal residual disease(MFC-MRD)-positive and 2 were MFC-MRD-negative.CAR-T cells were derived from patients’autologous lymphocytes.Nine patients were treated with CD19 CAR-T cells,and 12 were treated with CD19/CD22 CAR-T cells.After assessment on day 28 after CAR-T therapy,95.2%of the patients achieved complete remission,with an MRD-negative remission rate of 75%.Nineteen patients developed grade 0–2 cytokine release syndrome(CRS)and 2 patients suffered grade 3 CRS,all cases of which resolved after treatment.All patients underwent allo-HSCT after CAR-T therapy.The median time from CAR-T therapy to allo-HSCT was 63(38-114)days.Five patients experienced relapse after CAR-T therapy,including four with hematologic relapse and one with molecular relapse.The 3-year overall survival(OS)rates in the ABL1 and JAK-STAT groups were(83.3±15.2)%and(66.6±17.2)%,respectively(P=0.68).The 3-year relapse-free survival(RFS)rates were(50.0±20.4)%and(55.6±15.4)%in the ABL1 and JAK-STAT groups,respectively.There was no significant difference in 3-year OS or RFS between the two groups.Conclusions CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.