Ampatzidou Mirella, Florentin Lina, Papadakis Vassilios, Paterakis Georgios, Tzanoudaki Marianna, Bouzarelou Dimitra, Papadhimitriou Stefanos I, Polychronopoulou Sophia
Department of Pediatric Hematology-Oncology, "Aghia Sophia" Children's Hospital, 11527 Athens, Greece.
Alfa Laboratory Diagnostic Center, YGEIA Hospital, 11524 Athens, Greece.
Cancers (Basel). 2021 Jun 30;13(13):3289. doi: 10.3390/cancers13133289.
We present our data of a novel proposed CNA-profile risk-index, applied on a Greek ALLIC-BFM-treated cohort, aiming at further refining genomic risk-stratification. Eighty-five of 227 consecutively treated ALL patients were analyzed for the copy-number-status of eight genes (IKZF1/CDKN2A/2B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1). Using the MLPA-assay, patients were stratified as: (1) Good-risk(GR)-CNA-profile ( = 51), with no deletion of IKZF1/CDKN2A/B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1 or isolated deletions of ETV6/PAX5/BTG1 or ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. (2) Poor-risk(PR)-CNA-profile ( = 34), with any deletion of ΙΚΖF1/PAR1/EBF1/RB1 or any other CΝΑ. With a median follow-up time of 49.9 months, EFS for GR-CNA-profile and PR-CNA-profile patients was 96.0% vs. 57.6% ( < 0.001). For IR-group and HR-group patients, EFS for the GR-CNA/PR-CNA subgroups was 100.0% vs. 60.0% ( < 0.001) and 88.2% vs. 55.6% ( = 0.047), respectively. Among FC-MRD + patients (MRD ≥ 10), EFS rates were 95.3% vs. 51.7% for GR-CNA/PR-CNA subjects ( < 0.001). Similarly, among FC-MRD + patients (MRD ≥ 10), EFS was 92.9% vs. 27.3% ( < 0.001) and for patients FC-MRD - (MRD < 10), EFS was 97.2% vs. 72.7% ( = 0.004), for GR-CNA/PR-CNA patients, respectively. In a multivariate analysis, the CNA-profile was the most important outcome predictor. In conclusion, the CNA-profile can establish a new genomic risk-index, identifying a distinct subgroup with increased relapse risk among the IR-group, as well as a subgroup of patients with superior prognosis among HR-patients. The CNA-profile is feasible in BFM-based protocols, further refining MRD-based risk-stratification.
我们展示了一种新提出的拷贝数变异（CNA）谱风险指数的数据，该指数应用于希腊接受ALLIC - BFM治疗的队列，旨在进一步完善基因组风险分层。对连续治疗的227例ALL患者中的85例进行了8个基因（IKZF1/CDKN2A/2B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1）拷贝数状态的分析。使用MLPA检测，患者被分层为：（1）低风险（GR）-CNA谱（n = 51），无IKZF1/CDKN2A/B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1缺失，或ETV6/PAX5/BTG1的孤立缺失，或ETV6缺失并伴有BTG1/PAX5/CDKN2A/B中的一个额外缺失。（2）高风险（PR）-CNA谱（n = 34），有IKZF1/PAR1/EBF1/RB1的任何缺失或任何其他CNA。中位随访时间为49.9个月，GR - CNA谱和PR - CNA谱患者的无事件生存率（EFS）分别为96.0%和57.6%（P < 0.001）。对于IR组和HR组患者，GR - CNA/PR - CNA亚组的EFS分别为100.0%和60.0%（P < 0.001）以及88.2%和55.6%（P = 0.047）。在流式细胞术微小残留病（FC - MRD）阳性患者（MRD≥10）中，GR - CNA/PR - CNA受试者的EFS率分别为95.3%和51.7%（P < 0.001）。同样，在FC - MRD阳性患者（MRD≥10）中，GR - CNA/PR - CNA患者的EFS分别为92.9%和27.3%（P < 0.001）；对于FC - MRD阴性患者（MRD < 10），GR - CNA/PR - CNA患者的EFS分别为97.2%和72.7%（P = 0.004）。在多变量分析中，CNA谱是最重要的预后预测指标。总之，CNA谱可以建立一个新的基因组风险指数，识别IR组中复发风险增加的一个独特亚组，以及HR患者中预后较好的一个亚组。CNA谱在基于BFM的方案中是可行的，进一步完善了基于MRD的风险分层。
