Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.
目的： 分析IKZF1基因缺失在急性B淋巴细胞白血病（B-ALL）患者中的预后意义。 方法： 回顾性分析2016年3月至2019年9月南方医科大学附属南方医院收治的142例接受儿童样化疗方案的B-ALL患者的临床资料，分析IKZF1缺失患者的临床特征。无事件生存（EFS）和总生存（OS）的多因素分析使用Cox回归模型。将患者分为IKZF1缺失/单纯化疗组（A组）、IKZF1缺失/移植组（B组）、IKZF1非缺失/单纯化疗（C组）、IKZF1非缺失/移植（D组）四组比较患者生存。 结果： 142例患者，50例（35.2%）检出IKZF1基因缺失，其中4~7号外显子缺失占44.0%；与非缺失型比较，IKZF1缺失组B-ALL患者初诊时白细胞计数升高比例更高（52.0%对28.3%，P＝0.005）、诱导治疗第14天微小残留病转阴率更低（MRD(1)，40.0%对70.7%，P<0.001）以及Ph染色体阳性比例更高（52.0%对21.7%，P<0.001）。单因素分析显示，IKZF1缺失组3年EFS率、OS率明显低于IKZF1非缺失组[（37.1±7.3）%对（54.7±5.4）%，P＝0.025；（51.8±7.9）%对（73.9±4.7）%，P＝0.013]；多因素分析显示IKZF1缺失是影响B-ALL患者EFS（HR＝1.744，95%CI 1.082~2.812，P＝0.022）、OS（HR＝2.036，95%CI 1.119~3.705，P＝0.020）的独立危险因素。其中，A组的3年EFS、OS、无病生存率（DFS）均明显低于其他亚组。在IKZF1缺失患者中，接受异基因造血干细胞移植（allo-HSCT）组3年OS率为（67.9±10.4）%，3年EFS率为（46.6±10.5）%，均明显高于非移植组的（31.9±11.0）%和（26.7±9.7）%（P值分别为0.005、0.026）。 结论： IKZF1基因缺失的B-ALL患者整体预后差，儿童样化疗方案不能完全纠正IZKF1缺失对预后的不良影响；儿童样方案联合allo-HSCT可显著改善IKZF1缺失B-ALL的整体预后。.
Keywords: Allogeneic hematopoietic stem cell transplantation; Gene, IKZF1; Leukemia, B-cell, acute.