[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation]

Zhonghua Xue Ye Xue Za Zhi. 2021 Apr 14;42(4):318-323. doi: 10.3760/cma.j.issn.0253-2727.2021.04.009.
[Article in Chinese]

Abstract

Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

目的: 观察嵌合抗原受体T细胞(CART)序贯二次异基因造血干细胞移植(allo-HSCT)治疗移植后复发急性B淋巴细胞白血病(B-ALL)的疗效。 方法: 回顾性分析2015年10月至2020年6月在河北燕达陆道培医院接受二次allo-HSCT的41例B-ALL患者的临床资料,入选患者均为移植后骨髓形态学或髓外复发且二次移植前接受CART治疗。 结果: 全部41例患者中男21例、女20例,二次移植时中位年龄为16(3~46)岁。移植后骨髓复发31例(75.6%)、髓外复发5例(12.2%)、骨髓和髓外复发5例(12.2%)。复发后接受CD19-CART治疗35例(85.4%)、CD22-CART治疗2例(4.9%)、CD19-CART联合CD22-CART治疗4例(9.8%)。二次移植后预期3年总生存(OS)率为48.9%(95%CI 23.0%~70.6%)、无白血病生存(LFS)率为41.8%(95%CI 17.3%~64.9%),累积复发率(RI)为8.8%(95%CI 2.9%~26.4%),非复发相关死亡率(NRM)为51.1%(95%CI 31.2%~83.6%)。首次移植后复发时间≤6个月组(10例)二次移植后1年OS率低于复发时间>6个月组(31例)[45.0%(95%CI 12.7%~73.5%)对75.0%(95%CI 51.4%~88.8%),P=0.017]。 结论: CART序贯二次allo-HSCT可使部分造血干细胞移植后复发B-ALL患者获得长生存,但NRM较高,移植方案有待进一步改进。.

Keywords: Chimeric antigen receptor T-cell; Hematopoietic stem cell transplantation; Leukemia, B-cell lymphoblastic, acute; Relapse.

MeSH terms

  • B-Lymphocytes
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Recurrence
  • Retrospective Studies