《基于 Interfant-06 方案治疗伴有 - 重现性急性淋巴细胞白血病婴儿患者中微小残留病灶检测的临床意义》。
Clinical Implications of Minimal Residual Disease Detection in Infants With -Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol.
机构信息
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Center of Bioinformatics, Biostatistics and Bioimaging, University of Milano-Bicocca, Monza, Italy.
出版信息
J Clin Oncol. 2021 Feb 20;39(6):652-662. doi: 10.1200/JCO.20.02333. Epub 2021 Jan 6.
PURPOSE
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).
MATERIALS AND METHODS
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).
RESULTS
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).
CONCLUSION
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.
目的
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）。
材料与方法
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）。
结果
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）。
结论
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。
Zotero 插件