抗CD19 CAR-T细胞序贯异基因造血干细胞移植术治疗难治B淋巴细胞白血病疗效及安全性观察

Safety and efficacy of patients with refractory B-lymphoblastic leukemia treated with anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation

目的探讨抗CD19 CAR-T细胞治疗达深度缓解后序贯异基因造血干细胞移植(allo-HSCT)治疗难治B淋巴细胞白血病的疗效及不良反应。方法回顾性分析2017年11月至2019年3月河南省肿瘤医院收治的10例抗CD19 CAR-T细胞治疗达深度缓解后序贯allo-HSCT难治B淋巴细胞白血病患者的临床资料。结果①10例患者中,男5例,女5例,中位年龄23.5(10~31)岁,其中难治急性B淋巴细胞白血病(B-ALL)9例,慢性淋巴细胞白血病(CLL)1例。10例患者抗CD19 CAR-T细胞治疗后第30天及移植前评估微小残留病(MRD)均为阴性。②亲缘全相合移植2例,亲缘单倍型移植8例,抗CD19 CAR-T细胞治疗获得深度缓解至allo-HSCT中位时间为32.5(20~60)d。③10例患者获得造血重建,中性粒细胞植入中位时间为15(15~21)d,血小板植入中位时间为19(17~30)d。④预处理过程中,10例患者均未出现肝静脉闭塞病及出血性膀胱炎。1例患者出现渗漏综合征,予以限制入量、补充白蛋白及利尿等治疗后好转。移植过程中8例(80%)出现发热,均经抗感染治疗后好转。发生Ⅱ度急性移植物抗宿主病(aGVHD)2例,Ⅲ度aGVHD 1例;至随访截止9例存活患者中8例出现局限性慢性移植物抗宿主病。⑤中位随访262(150~540)d,预期1年总生存率为(90.0±1.0)%,无病生存率为(85.7±1.3)%。结论抗CD19 CAR-T细胞治疗达深度缓解后序贯allo-HSCT可作为难治B淋巴细胞白血病患者的可选治疗方案。

Objective To investigate the efficacy and side effects of anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation(allo-HSCT)regimen for refractory B-lymphoblastic leukemia.Methods 10 patients with refractory B-lymphoblastic leukemia with minimal residual disease(MRD)negative after anti-CD19 CAR-T cell treatment,then bridging to allo-HSCT from November 2017 to March 2019 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed.Results①Among 10 patients,5 were males and 5 females,with a median age of 23.6(10-31)years.9 patients were diagnosed refractory acute lymphoblastic leukemia and the other one was chronic lymphoblastic leukemia.10 patients reached MRD negative 30 days after anti-CD19 CAR-T cell.②The donors were identical sibling(2 cases)and haploidentical family member(8 cases).The median time from MRD negative after CAR-T treatment to transplantation were 32.5(20-60)days.③10 patients obtained complete haploidentical engraftment.The median time of neutrophil implantation was 15(15-21)days,and 19(17-30)days of platelet implantation.④After conditioning,no hepatic venoocclusive disease and hemorrhagic cystitis occurred.One patient had leakage syndrome and got improved after intervention such as limited water entry,albumin supplementation and diuresis.8(80%)patients had fever,2 cases experienced acute graft-versus-host disease(GVHD)gradeⅡ,1 case with aGVHD gradeⅢ.Among 9 survivals,localized chronic GVHD occurred in 8 patients.⑤The median follow-up was 262(150-540)days and the estimated 1-years overall survivaln(OS)and disease free survival(DFS)were(90.0±1.0)%and(85.7±1.3)%,respectively.Conclusion Anti-CD19 CAR-T cell bridging to allo-HSCT regimen is a feasible choice with favorable outcome for refractory B-lymphoblastic leukemia.