INTRODUCTION The role of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients with relapsed or refractory (R/R) ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of ETV6/RUNX1-positive ALL. METHODS We analyzed the clinical characteristics and treatment outcomes of 20 pediatric patients who were diagnosed with ETV6/RUNX1-positive ALL and received chemotherapy/chimeric antigen receptor T-cell bridged to haplo-HSCT between 2016 and 2021 at our institution. RESULTS With a median follow-up time of 47 months, the 3-year cumulative incidence of relapse, disease-free survival, and overall survival were 35.9% (95% confidence interval (CI): 15.3-57.1%), 59.1% (95% CI: 37.2-81.0%), and 75.0% (95% CI: 56.0-94.0%), respectively. Multivariate analysis revealed that pre-HSCT measurable residual disease (MRD) positivity (hazard ratio, 13.275; 95% CI: 2.406-73.243; p = 0.003) had a significant negative impact on relapse. A total of 7 patients experienced positive ETV6/RUNX1 gene expression at a median of 7.2 months after haplo-HSCT, and 5 of them experienced relapse at a median time of 12.1 months after haplo-HSCT. ROC curve analysis was performed to analyze the significance of pre-HSCT and post-HSCT ETV6/RUNX1 transcripts for predicting relapse; the AUC were 0.798 (95% CI: 0.567-1.0, p = 0.035) and 0.875 (95% CI: 0.690-1.0, p = 0.008), respectively. The optimal cut-off points to predict an inevitable relapse were 0.011% and 0.0019%, respectively. CONCLUSION Patients with R/R ETV6/RUNX1-positive ALL may benefit from haplo-HSCT. Deeply eliminating pre-HSCT MRD and preemptive treatment for post-HSCT MRD may be crucial to further improving the prognosis.

中文翻译：

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单倍体同种异体造血干细胞移植治疗儿童复发或难治性 ETV6/RUNX1 阳性急性淋巴细胞白血病的结果和预后因素。


简介 单倍体同种异体造血干细胞移植 (haplo-HSCT) 在复发或难治性 (R/R) ETV6/RUNX1 阳性急性淋巴细胞白血病 (ALL) 儿科患者中的作用尚不清楚。本研究旨在确定预后因素并探讨单倍体造血干细胞移植（haplo-HSCT）在治疗 ETV6/RUNX1 阳性 ALL 中的作用。方法 我们分析了 2016 年至 2021 年间在我们机构诊断为 ETV6/RUNX1 阳性 ALL 并接受化疗/嵌合抗原受体 T 细胞桥接到单倍体 HSCT 的 20 名儿科患者的临床特征和治疗结果。结果 中位随访时间为 47 个月，3 年累积复发率、无病生存率和总生存率分别为 35.9%（95% 置信区间 (CI)：15.3-57.1%）、59.1%（分别为 95% CI：37.2-81.0%）和 75.0%（95% CI：56.0-94.0%）。多变量分析显示，HSCT 前可测量残留病 (MRD) 阳性（风险比，13.275；95% CI：2.406-73.243；p = 0.003）对复发有显着的负面影响。共有 7 名患者在 haplo-HSCT 后中位时间 7.2 个月时出现 ETV6/RUNX1 基因阳性表达，其中 5 名患者在 haplo-HSCT 后中位时间 12.1 个月时出现复发。进行ROC曲线分析，分析HSCT前和HSCT后ETV6/RUNX1转录本对预测复发的意义； AUC 分别为 0.798（95% CI：0.567-1.0，p = 0.035）和 0.875（95% CI：0.690-1.0，p = 0.008）。预测不可避免的复发的最佳临界点分别是 0.011% 和 0.0019%。结论 R/R ETV6/RUNX1 阳性 ALL 患者可能受益于单倍体 HSCT。 深度消除HSCT前MRD和针对HSCT后MRD的超前治疗对于进一步改善预后可能至关重要。