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<p>While <i>ETV6</i>::<i>RUNX1</i>-positive acute lymphoblastic leukemia (ALL) is generally associated with favorable outcomes, a subset of patients experience relapse despite receiving standard therapy, underscoring the need for early biomarkers to identify high-risk subgroups. In this retrospective study of 345 consecutive pediatric patients with <i>ETV6</i>::<i>RUNX1</i>-positive ALL treated in accordance with the protocol of the Chinese Children’s Leukemia Group (CCLG-ALL 2008), CD33 expression (CD33<sup>+</sup>) on leukemic blasts was detected in 55.9% of patients and was significantly associated with minimal residual disease (MRD) positivity on day 15 (D15-MRD-positive) (65.2% vs. 42.0%, <i>P</i> &lt; 0.001). Multivariate analysis revealed CD33<sup>+</sup> status as an independent risk factor for D15-MRD positivity (odds ratio (OR) = 2.66, 95% confidence interval (CI) 1.66–4.26). Among CD33<sup>+</sup> patients, those who were D15-MRD-positive had significantly inferior 5-year and 10-year event-free survival (EFS) relative to those who were D15-MRD-negative (5-year EFS: 91.9% ± 2.4% vs. 100%, <i>P</i> = 0.027; 10-year EFS: 89.2% ± 3.0% vs. 100%, <i>P</i> = 0.014). This prognostic association was not observed in CD33-negative patients. In conclusion, the combination of CD33<sup>+</sup> and D15-MRD-positivity may identify a distinct high-risk subgroup within <i>ETV6</i>::<i>RUNX1</i>-positive ALL. Early intervention, potentially including CD33-directed therapy, may represent a promising strategy to improve outcomes in this subgroup, although further validation is warranted.</p>

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CD33 expression combined with D15-MRD positivity identifies poor prognosis in children with ETV6::RUNX1-positive ALL

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月29日

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  • Xueling Zheng,
  • Yuxi Luo,
  • Ruidong Zhang,
  • Xiaohang Liu,
  • Pengli Huang,
  • Chao Gao,
  • Hui Chen,
  • Jia Fan,
  • Wei Lin,
  • Jiaole Yu,
  • Yuanyuan Zhang,
  • Peijing Qi,
  • Ying Wu,
  • Xiaoxi Zhao,
  • Jun Li,
  • Xiaoxia Peng,
  • Tianyou Wang,
  • Huyong Zheng

摘要

While ETV6::RUNX1-positive acute lymphoblastic leukemia (ALL) is generally associated with favorable outcomes, a subset of patients experience relapse despite receiving standard therapy, underscoring the need for early biomarkers to identify high-risk subgroups. In this retrospective study of 345 consecutive pediatric patients with ETV6::RUNX1-positive ALL treated in accordance with the protocol of the Chinese Children’s Leukemia Group (CCLG-ALL 2008), CD33 expression (CD33+) on leukemic blasts was detected in 55.9% of patients and was significantly associated with minimal residual disease (MRD) positivity on day 15 (D15-MRD-positive) (65.2% vs. 42.0%, P < 0.001). Multivariate analysis revealed CD33+ status as an independent risk factor for D15-MRD positivity (odds ratio (OR) = 2.66, 95% confidence interval (CI) 1.66–4.26). Among CD33+ patients, those who were D15-MRD-positive had significantly inferior 5-year and 10-year event-free survival (EFS) relative to those who were D15-MRD-negative (5-year EFS: 91.9% ± 2.4% vs. 100%, P = 0.027; 10-year EFS: 89.2% ± 3.0% vs. 100%, P = 0.014). This prognostic association was not observed in CD33-negative patients. In conclusion, the combination of CD33+ and D15-MRD-positivity may identify a distinct high-risk subgroup within ETV6::RUNX1-positive ALL. Early intervention, potentially including CD33-directed therapy, may represent a promising strategy to improve outcomes in this subgroup, although further validation is warranted.