提高化疗强度对伴IKZF1基因缺失儿童急性淋巴细胞白血病预后的影响

目的 总结伴IKZF1基因缺失儿童急性淋巴细胞白血病（ALL）的临床特征并观察提高化疗强度对其预后的影响。方法 2015年12月至2018年2月间确诊并按照中国儿童白血病协作组-ALL 2008（CCLG-ALL 2008）方案规范治疗的ALL患儿共278例，根据有无IKZF1基因缺失将其分为IKZF1基因缺失组和IKZF1基因正常组，IKZF1基因缺失组均接受CCLG-ALL 2008高危（HR）方案治疗，IKZF1基因正常组则按临床危险度分型接受不同强度化疗，比较两组的临床特征及无事件生存（EFS）率。结果 278例患儿中共24例（8.6%）检出IKZF1基因外显子大片段缺失。IKZF1基因缺失组初诊时WBC ≥ 50×10⁹/L、BCR-ABL1融合基因阳性、诱导缓解治疗第15天微小残留病≥ 10%、微小残留病-HR、临床危险度-HR所占比例均高于IKZF1基因正常组（P < 0.05）。IKZF1基因缺失组3年EFS率（76%±10%）低于IKZF1基因正常组（84%±4%），但差异无统计学意义（P=0.282）；其中，IKZF1基因缺失组-非HR（实际按CCLG-ALL 2008 HR方案化疗）的预计3年EFS率为82%±12%，低于IKZF1基因正常组-非HR（86%±5%），但差异无统计学意义（P=0.436）。结论 伴IKZF1基因缺失的儿童ALL早期治疗反应更差，提高化疗强度可能改善其预后。

Effect of increasing the intensity of chemotherapy on the prognosis of acute lymphoblastic leukemia in children with IKZF1 deletion

Objective To study the clinical features of acute lymphoblastic leukemia (ALL) in children with IKAROS family zinc finger 1 (IKZF1) deletion, and to observe the effect of increasing the intensity of chemotherapy on the prognosis of this disease. Methods A total of 278 children diagnosed with ALL between December 2015 and February 2018 were systematically treated according to the Chinese Children's Leukemia Group-ALL 2008 protocol (CCLG-ALL 2008). The patients were divided into an IKZF1-deleted group and a control group according to the presence or absence of IKZF1. The IKZF1-deleted group was treated with the regimen for high-risk group (HR) in the CCLG-ALL 2008 protocol, while the control group received different intensities of chemotherapy according to clinical risk classification. The clinical features and event-free survival rate (EFS) were compared between the two groups. Results A total of 24 (8.6%) cases of 278 children were found to have large deletions of exons of the IKZF1 gene. The IKZF1-deleted group had significantly higher proportions of cases with white blood cell count ≥ 50×109/L at initial diagnosis, BCR-ABL1 fusion gene positive, minimal residual disease ≥ 10% on the 15th day of induction remission treatment, minimal residual disease-high risk and clinical risk classification-high risk compared with the control group (P < 0.05). The 3-year EFS rate (76%±10%) in the IKZF1-deleted group was lower than that in the control group (84%±4%), but with no significant difference between the two groups (P=0.282). The estimated 3-year EFS rate in the IKZF1-deleted-non-HR group (actually treated with the chemotherapy regimen for HR in the CCLG-ALL 2008 protocol) was 82%±12%, which was lower than that in the control-non-HR group (86%±5%), but there was no significant difference (P=0.436). Conclusions ALL children with IKZF1 deletion have worse early treatment response, and increasing the intensity of chemotherapy might improve the prognosis.