Outcome and Prognostic Factors of Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Relapsed or Refractory ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia.

ABSTRACT

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.