Department of Hematology, Beijing Boren Hospital, Beijing, China.
Cytology Laboratory, Beijing Boren Hospital, Beijing, China.
Am J Hematol. 2021 Jun 1;96(6):671-679. doi: 10.1002/ajh.26160. Epub 2021 Mar 29.
The prognosis of relapsed acute lymphoblastic leukemia (ALL) after allogeneic transplantation is dismal when treated with conventional approaches. While single-target CD19 or CD22 chimeric antigen receptor (CAR) T-cell therapy has achieved high complete remission (CR) rates in refractory/relapsed B-ALL, it could not maintain a durable remission in most patients. To prolong relapse-free survival, we sequentially combined CD19 and CD22 CAR-T cells to treat post-transplant relapsed B-ALL patients with both CD19/CD22 antigen expression on lymphoblasts. Patient-derived donor cells were collected to produce CAR-T cells that were transfected by lentiviral vectors encoding second generation CARs composed of CD3ζ and 4-1BB. The second T-cell infusion was scheduled at least 1 month, and usually within 6 months after the first CAR-T treatment. Twenty-seven adult and pediatric patients, including 11 (41%) with extramedullary diseases (EMD), received the first CD19 CAR-T and 23 (85%) achieved CR. Subsequently, 21 out of 27 patients received the second CD22 CAR-T and were followed-up for a median of 19.7 (range, 5.6-27.3) months; 14 cases remained in CR, seven relapsed and two of them died from disease progression; Kaplan-Meier survival analysis showed overall survival and event-free survival rates of 88.5% and 67.5%, respectively, at both 12 months and 18 months. CAR-T associated graft-versus-host disease (GVHD) occurred in 23% of patients, with 8% new-onset acute GVHD and 15% persistent or worsened pre-existing cGVHD before CAR-T. This combination strategy of sequential CD19 and CD22 CAR-T therapy significantly improved the long-term survival in B-ALL patients who relapsed after transplantation.
异基因移植后复发的急性淋巴细胞白血病（ALL）的预后在采用传统方法治疗时非常差。虽然单靶点 CD19 或 CD22 嵌合抗原受体（CAR）T 细胞疗法在难治/复发 B-ALL 中已实现了高完全缓解（CR）率，但在大多数患者中无法维持持久缓解。为了延长无复发生存时间，我们序贯联合 CD19 和 CD22 CAR-T 细胞治疗具有淋巴母细胞上 CD19/CD22 抗原表达的移植后复发 B-ALL 患者。采集患者来源的供体细胞以产生 CAR-T 细胞，这些细胞通过慢病毒载体转染，该载体编码由 CD3ζ 和 4-1BB 组成的第二代 CAR。第二次 T 细胞输注计划至少在第一次 CAR-T 治疗后 1 个月，通常在 6 个月内进行。27 例成人和儿童患者，包括 11 例（41%）有髓外疾病（EMD），接受了第一次 CD19 CAR-T 治疗，23 例（85%）达到了 CR。随后，27 例患者中有 21 例接受了第二次 CD22 CAR-T 治疗，并进行了中位随访 19.7（范围，5.6-27.3）个月；14 例仍处于 CR 状态，7 例复发，其中 2 例因疾病进展而死亡；Kaplan-Meier 生存分析显示，12 个月和 18 个月时的总生存率和无事件生存率分别为 88.5%和 67.5%。CAR-T 相关移植物抗宿主病（GVHD）发生在 23%的患者中，8%发生新发急性 GVHD，15%在 CAR-T 之前存在持续性或加重的慢性 GVHD。这种序贯 CD19 和 CD22 CAR-T 治疗的联合策略显著改善了移植后复发的 B-ALL 患者的长期生存。
