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.

中文翻译：

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嵌合抗原受体T细胞疗法治疗复发/难治性B细胞急性淋巴细胞白血病后的巩固异体造血干细胞移植：谁？什么时候？为什么？

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）患者中显示出良好的疗效，但它无法改善无白血病的长期生存（ LFS）。CAR T细胞疗法后的同种异体造血干细胞移植（allo-HSCT）已经成为延长LFS的有希望的策略。然而，哪些患者可能受益于巩固的allo-HSCT，以及最佳的治疗窗口，仍有待探索。最近的临床数据表明，通过流式细胞术在骨髓中具有复杂的核型，不良基因和高输注前最小残留疾病（MRD）的患者在CAR T细胞治疗后复发的风险很高。淋巴结清除前乳酸脱氢酶高，淋巴结清除前血小板计数低，CAR T细胞输注后骨髓中氟达拉滨的缺乏，通过高通量测序在骨髓中持续的白血病序列以及CAR T细胞的早期丢失也与CAR T细胞治疗后的复发有关。在具有这些危险因素的患者中，CAR T细胞治疗后合并allo-HSCT可能会延长LFS。Allo-HSCT通常在CAR T细胞治疗后三个月内为MRD阴性完全缓解的患者提供最佳的临床益处。在这里，我们总结了抗CD19 CAR T细胞治疗后合并allo-HSCT的临床数据，以及与allo-HSCT受益相关的潜在因素。我们还讨论了合并allo-HSCT的最佳治疗窗口和方案。最后，最重要的是