Hematologic Diseases Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
National Key Discipline of Pediatrics, Capital Medical University, Beijing, China.
Ann Hematol. 2024 Sep;103(9):3657-3665. doi: 10.1007/s00277-024-05687-y. Epub 2024 Mar 18.
Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1 patients with TP1 MRD < 10 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.
基于微小残留病（MRD）的风险分层标准在儿童急性淋巴细胞白血病（ALL）的特定基因亚型中仍不明确。在接受中国儿童白血病协作组 CCLG-2008 方案治疗的 723 例新发 ALL 患儿中，在诱导结束时（时间点 1，TP1）和巩固治疗前（TP2）评估了 MRD，不同融合基因或免疫表型患者的 MRD 水平差异显著（P 均<0.001）。此外，MRD 的预后影响因不同的分子亚型而异。我们根据结果将每个分子亚型的患者分为两组 MRD 组。对于携带 BCR::ABL1 或 KMT2A 重排的患者，我们将 TP1 和 TP2 时 MRD<10 的患者分为低 MRD 组，其余患者分为高 MRD 组。TP1 MRD<10 和 TP2 MRD 阴性的 ETV6::RUNX1 患者被分为低 MRD 组，其余患者被分为高 MRD 组。对于 T-ALL，我们将 TP1 MRD≥10 的患儿定义为高 MRD 组，其余患儿定义为低 MRD 组。低 MRD 组的 10 年无复发生存率显著优于高 MRD 组。我们在接受 BCH-ALL2003 方案治疗的患者中验证了基于亚型特异性 MRD 的分层的预后影响。总之，基于亚型特异性 MRD 的风险分层可能有助于儿童 ALL 的精确治疗。
