文章：

早期BCR::ABL1水平降低作为儿童慢性期慢性粒细胞白血病深度分子反应的预测指标

EarlyBCR::ABL1Reduction as a Predictor of Deep Molecular Response in Pediatric Chronic-Phase Chronic Myeloid Leukemia

原文发布日期：15 December 2025

DOI: 10.3390/cancers17243994

类型: Article

开放获取: 是

英文摘要：

Background: Tyrosine kinase inhibitors (TKIs) have transformed the prognosis of chronic myeloid leukemia (CML), but pediatric patients face unique challenges due to prolonged exposure. Early molecular response (EMR,BCR::ABL1≤ 10% at 3 months) is a recognized predictor of favorable outcomes in adults and has been correlated with improved responses in children. However, its relationship with achieving deep molecular remission (DMR,BCR::ABL1≤ 0.01%) in pediatric CML remains unclear.Methods: We performed a single-center, retrospective analysis of 103 pediatric patients with chronic-phase CML treated with frontline TKIs. Among them, 88 were evaluable for molecular response.BCR::ABL1transcript levels were quantified by real-time quantitative PCR on the International Scale, and molecular responses were assessed. Associations between early molecular dynamics and long-term outcomes were evaluated using Kaplan–Meier and cumulative incidence analyses.Results: At 3 months, 64.8% achieved EMR. Early responders had significantly higher MMR rates at 12 months (80.8% vs. 5.6%;p= 0.00018) and DMR at 24 months (70.4% vs. 42.2%;p= 0.029). The ≥0.45-log reduction inBCR::ABL1transcripts at 3 months predicted shorter times to MMR (median 11 vs. 29 months) and DMR (18 vs. 50 months), as well as higher overall MMR (p= 0.011) and DMR (p= 0.014) incidences. Bone marrow fibrosis correlated with inferior molecular outcomes (p= 0.017 for MMR).Conclusions: EarlyBCR::ABL1decline kinetics independently predict molecular depth in pediatric CML. Quantitative early transcript reduction may guide risk-adapted management and optimize long-term TKI strategies in children.

摘要翻译： 

背景：酪氨酸激酶抑制剂（TKI）已显著改善慢性髓系白血病（CML）的预后，但儿童患者因长期用药面临独特挑战。早期分子学反应（EMR，即3个月时BCR::ABL1≤10%）是公认的成人预后良好预测指标，且与儿童患者治疗反应改善相关，但其与儿童CML患者获得深度分子学缓解（DMR，BCR::ABL1≤0.01%）的关系尚不明确。 方法：我们对103例接受一线TKI治疗的慢性期儿童CML患者进行单中心回顾性分析，其中88例可评估分子学反应。采用国际标准化实时定量PCR检测BCR::ABL1转录本水平并评估分子学反应，通过Kaplan-Meier法和累积发生率分析评估早期分子动力学与长期结局的关联。 结果：3个月时64.8%患者达到EMR。早期应答者在12个月时获得主要分子学缓解（MMR）的比例显著更高（80.8% vs. 5.6%；p=0.00018），24个月时DMR获得率也更高（70.4% vs. 42.2%；p=0.029）。3个月时BCR::ABL1转录本下降≥0.45-log可预测更短的MMR中位时间（11个月 vs. 29个月）和DMR中位时间（18个月 vs. 50个月），以及更高的总体MMR（p=0.011）和DMR（p=0.014）发生率。骨髓纤维化与较差的分子学结局相关（MMR：p=0.017）。 结论：早期BCR::ABL1下降动力学可独立预测儿童CML的分子学缓解深度。早期转录本定量下降指标可指导风险适应性管理，优化儿童长期TKI治疗策略。

原文链接：

EarlyBCR::ABL1Reduction as a Predictor of Deep Molecular Response in Pediatric Chronic-Phase Chronic Myeloid Leukemia