Jiang Huiwen, Hu Yu, Mei Heng
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
Biomark Res. 2020 Nov 25;8(1):66. doi: 10.1186/s40364-020-00247-8.
Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR T-cell therapy has emerged as a promising strategy to prolong LFS. Nevertheless, which patients are likely to benefit from consolidative allo-HSCT, as well as the optimal therapeutic window, remain to be explored. Recent clinical data indicate that patients with complex karyotypes, adverse genes, and high pre-infusion minimal residual disease (MRD) by flow cytometry in the bone marrow, were at high risk of relapse after CAR T-cell therapy. High pre-lymphodepletion lactate dehydrogenase, low pre-lymphodepletion platelet count, absence of fludarabine in lymphodepletion, persistent leukemic sequence by high throughput sequencing in bone marrow after CAR T-cell infusion, and early loss of CAR T cells have also been linked to relapse after CAR T-cell therapy. In patients having these risk factors, consolidative allo-HSCT after CAR T-cell therapy may prolong LFS. Allo-HSCT provides optimal clinical benefit in patients with MRD-negative complete remission, typically within three months after CAR T-cell therapy. Herein, we summarize the clinical data on consolidative allo-HSCT after anti-CD19 CAR T-cell therapy, as well as the potential factors associated with allo-HSCT benefit. We also discuss the optimal therapeutic window and regimen of consolidative allo-HSCT. Finally, and most importantly, we provide recommendations for the assessment and management of r/r B-ALL patients undergoing anti-CD19 CAR T-cell therapy.
尽管抗CD19嵌合抗原受体（CAR）T细胞疗法在复发/难治性B细胞急性淋巴细胞白血病（r/r B-ALL）患者中显示出良好疗效，但未能改善长期无白血病生存期（LFS）。CAR T细胞治疗后进行异基因造血干细胞移植（allo-HSCT）已成为延长LFS的一种有前景的策略。然而，哪些患者可能从巩固性allo-HSCT中获益以及最佳治疗窗仍有待探索。最近的临床数据表明，具有复杂核型、不良基因以及骨髓流式细胞术检测显示输注前微小残留病（MRD）高的患者，在CAR T细胞治疗后复发风险高。输注前乳酸脱氢酶高、输注前血小板计数低、淋巴细胞清除方案中无氟达拉滨、CAR T细胞输注后骨髓高通量测序显示白血病序列持续存在以及CAR T细胞早期丢失也与CAR T细胞治疗后复发有关。在有这些危险因素的患者中，CAR T细胞治疗后进行巩固性allo-HSCT可能延长LFS。allo-HSCT在MRD阴性完全缓解的患者中可提供最佳临床获益，通常在CAR T细胞治疗后三个月内。在此，我们总结抗CD19 CAR T细胞治疗后巩固性allo-HSCT的临床数据以及与allo-HSCT获益相关的潜在因素。我们还讨论巩固性allo-HSCT的最佳治疗窗和方案。最后，也是最重要的，我们为接受抗CD19 CAR T细胞治疗的r/r B-ALL患者的评估和管理提供建议。
