Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Center of Bioinformatics, Biostatistics and Bioimaging, University of Milano-Bicocca, Monza, Italy.
J Clin Oncol. 2021 Feb 20;39(6):652-662. doi: 10.1200/JCO.20.02333. Epub 2021 Jan 6.
Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with -rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).
MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged , immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10), and high (≥ 5 × 10).
EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively ( = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively ( < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively ( < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9).
This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.
婴儿急性淋巴细胞白血病（ALL）的特征是基因重排发生率高，预后不良。我们评估了 - 重排 ALL 患儿在 Interfant-06 方案中接受治疗时微小残留病（MRD）的价值，该方案比较了淋巴样巩固（方案 IB）与髓样巩固（阿糖胞苷、柔红霉素、依托泊苷/米托蒽醌、阿糖胞苷、依托泊苷）。
通过基于 DNA 的聚合酶链反应，对 249 名婴儿的重排 、免疫球蛋白和/或 T 细胞受体基因在诱导结束（EOI）和巩固结束（EOC）时进行 MRD 检测。MRD 结果分为阴性、中间（<5×10）和高（≥5×10）。
EOI MRD 水平可预测预后，阴性、中间和高 EOI MRD 水平的患儿 6 年无病生存率（DFS）分别为 60.2%（95%CI，43.2 至 73.6）、45.0%（95%CI，28.3 至 53.1）和 33.8%（95%CI，23.8 至 44.1）（=0.0039）。EOC MRD 水平也可预测预后，阴性、中间和高 EOC MRD 水平的患儿 6 年 DFS 分别为 68.2%（95%CI，55.2 至 78.1）、40.1%（95%CI，28.1 至 51.9）和 11.9%（95%CI，2.6 至 29.1）（<0.0001）。根据巩固治疗类型对 EOI MRD 进行分析显示，接受淋巴样巩固治疗的患儿 6 年 DFS 分别为 78.2%（95%CI，51.4 至 91.3）、47.2%（95%CI，33.0 至 60.1）和 23.2%（95%CI，12.1 至 36.4）（<0.0001），而接受髓样巩固治疗的患儿相应数字分别为 45.0%（95%CI，23.9 至 64.1）、41.3%（95%CI，23.2 至 58.5）和 45.9%（95%CI，29.4 至 60.9）。
本研究支持诱导治疗可选择后续治疗患者的观点；EOI MRD 较高的患儿可能受益于 AML 样巩固（DFS 45.9%比 23.2%），而 EOI MRD 较低的患儿可能受益于 ALL 样巩固（DFS 78.2%比 45.0%）。EOC MRD 阳性的患儿预后不良。这些发现将用于下一个 Interfant 方案的治疗干预。
