Abstract：
Treatment outcomes for children with relapsed and refractory acute lymphoblastic leukemia (R/R-ALL) remain poor, and the optimal induction therapy has not been determined. Bortezomib is a proteasome inhibitor that acts synergistically and additively with standard chemotherapy for ALL. We evaluated the efficacy and safety of combination chemotherapy with bortezomib in children with R/R-ALL. This single-arm, multicenter, phase 2 study was conducted in Japan between 2016 and 2020. Eligible patients were divided into two cohorts: a high-risk first-relapse cohort of untreated patients with high-risk first-relapsed ALL and an expansion cohort of patients with refractory ALL, including multiple relapses, relapse after allogeneic hematopoietic cell transplantation, and induction failure. All patients received a single course of chemotherapy as induction therapy. Sixteen patients (10 in the high-risk first-relapse cohort, six in the expansion cohort) were evaluable. The overall remission rate after induction therapy was 60% in the high-risk first-relapse cohort and 16.7% in the expansion cohort. All patients had minimal residual disease. Adverse events were acceptable except for interstitial lung disease and hypoxia in a patient in the expansion cohort, but addition of bortezomib to conventional chemotherapy did not produce obvious improvement in children with R/R-ALL.
摘要：
儿童复发性和难治性急性淋巴细胞白血病（R/R-ALL）的治疗结果仍然很差。最佳诱导疗法尚未确定。硼替佐米是一种蛋白酶体抑制剂，与ALL的标准化疗协同作用和相加作用。我们评估了硼替佐米联合化疗对R/R-ALL患儿的疗效和安全性。这个单臂，多中心，第二阶段研究于2016年至2020年在日本进行。符合条件的患者分为两个队列：高风险首次复发队列，包括未治疗的高风险首次复发ALL患者和难治性ALL患者的扩展队列。包括多次复发,异基因造血细胞移植后复发，和感应失败。所有患者均接受单疗程化疗作为诱导治疗。16例患者（高危首次复发队列中有10例，扩展队列中有6人)可评估。在高风险首次复发队列中，诱导治疗后的总体缓解率为60％，在扩展队列中为16.7％。所有患者均有微小残留病。扩展队列患者的不良事件是可接受的，除了间质性肺病和缺氧，但在R/R-ALL患儿中,在常规化疗的基础上加用硼替佐米并没有明显改善.
