背景:IKZF1del在小儿B细胞前体急性淋巴细胞白血病(BCP-ALL)中的预测重要性已显示出不同研究的差异。因此,IKZF1delBCP-ALL儿童的最佳治疗方法仍然存在争议,围绕使用基于IKZF1del的高危分层与微小残留病(MRD)指导方案的争论正在进行。
方法:使用从福建四家医院获得的多重连接依赖性探针扩增(MLPA)数据,可靠地确定了804例患者的IKZF1状态。中国的一个省。在中国儿童白血病组(CCLG)-ALL2008队列中,IKZF1状态包含在风险分配中,所有IKZF1del患者都接受了高风险方案。相反,在中国儿童癌症组(CCCG)-所有2015年队列中,IKZF1del没有纳入风险分配,根据MRD指导的风险分层方案对患者进行治疗.
结果:在86例患者(86/804,10.7%)和30例(30/46,65.2%)BCR::ABL1阳性患者中发现了IKZF1del。总的来说,IKZF1del是患者预后不良的预测因子,虽然随着年龄调整的重要性减弱,诊断时的白细胞(WBC)计数,治疗组,和MRD状态。在CCLG-ALL2008队列中,与IKZF1wt相比,IKZF1del的5年总生存率(OS)和无事件生存率(EFS)明显较低,5年累积复发率(CIR)明显较高。在CCLG-ALL2015队列中,与IKZF1wt相比,IKZF1del具有较低的5年OS和EFS以及较高的5年CIR,但是差异微不足道。与MRD指导方案(CCCG-ALL2015方案)相比,接受更高强度化疗(CCLG-ALL2008高风险方案)治疗的IKZF1del患者的5年OS和EFS明显较低。此外,接受CCLG-ALL2008高风险方案治疗的患者出现严重不良事件(SAE)的频率更高,尤其是感染相关的SAE,与接受CCCG-ALL2015MRD指导方案治疗的患者相比.
结论:IKZF1del的预后效果在不同方案中可能有所不同。与高强度化疗相比,MRD指导方案可能是用IKZF1del治疗儿童BCP-ALL的更有效方法.
BACKGROUND: The predictive importance of IKZF1del in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has shown variability across different studies. Thus, the optimal treatment approach for children with IKZF1del BCP-ALL remains contentious, with the ongoing debate surrounding the use of IKZF1del-based high-risk stratification versus a minimal residual disease (MRD)-guided protocol.
METHODS: IKZF1 status was reliably determined in 804 patients using multiplex ligation-dependent probe amplification (MLPA) data obtained from four hospitals in Fujian, a province of China. In the Chinese Children Leukemia Group (CCLG)-ALL 2008 cohort, IKZF1 status was included in the risk assignment, with all IKZF1del patients receiving a high-risk regimen. Conversely, in the Chinese Children\'s Cancer Group (CCCG)-ALL 2015 cohort, IKZF1del was not incorporated into the risk assignment, and patients were treated based on an MRD-guided risk stratification protocol.
RESULTS: IKZF1del was found in 86 patients (86/804, 10.7%) overall and in 30 (30/46, 65.2%) BCR::ABL1-positive patients. Overall, IKZF1del was a poor prognostic predictor for patients, though the significance diminished upon age adjustment, white blood cell (WBC) count at diagnosis, treatment group, and MRD status. In the CCLG-ALL 2008 cohort, IKZF1del conferred a notably lower 5-year overall survival (OS) and event-free survival (EFS) and a significantly higher 5-year cumulative incidence of relapse (CIR) than IKZF1wt. In the CCLG-ALL 2015 cohort, IKZF1del conferred a lower 5-year OS and EFS and a higher 5-year CIR than IKZF1wt, but the differences were insignificant. The IKZF1del patients treated with higher intensity chemotherapy (CCLG-ALL 2008 high-risk regimen) had a markedly lower 5-year OS and EFS compared with those treated with the MRD-guided protocol (CCCG-ALL 2015 protocol). Furthermore, patients treated with the CCLG-ALL 2008 high-risk regimen experienced a higher frequency of serious adverse events (SAEs), especially infection-related SAEs, compared with those treated with the CCCG-ALL 2015 MRD-guided protocol.
CONCLUSIONS: The prognostic effect of IKZF1del may vary in different protocols. Compared with higher intensity chemotherapy, the MRD-guided protocol may be a more effective approach to treating BCP-ALL with IKZF1del in children.