Kuang Wen-Yong, Zheng Min-Cui, Li Wan-Li, Yang Hai-Xia, Zhang Ben-Shan, Wu Pan
Department of Hematology, Hunan Children's Hospital, Changsha 410007, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 Jul;20(7):538-542. doi: 10.7499/j.issn.1008-8830.2018.07.005.
To study the effects of minimal residual disease (MRD) level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia (B-ALL).
A total of 152 children with newly-diagnosed B-ALL who had complete remission after the first cycle of the chemotherapy and had complete follow-up information were enrolled in this study. According to the MRD detection by flow cytometry on day 33 of remission induction, they were divided into three groups: standard-risk (SR) group (MRD <10; n=60), intermediate-risk (IR) group (10≤ MRD <10; n=55), and high-risk (HR) group (MRD ≥10; n=37). Nested RT-PCR was used to determine the IKZF1 genotype of all children before chemotherapy. The effects of MRD level on day 33 of remission induction and IKZF1 genotype on the recurrence-free survival (RFS) of children with B-ALL were analyzed.
There were 7 common IKZF1 subtypes in all the 152 children with B-ALL: IK1, IK2/3, IK4, IK6, IK8, IK9, and IK10. Of the 152 children, 130 had functional subtypes of IKZF1 and 22 had non-functional subtypes of IKZF1. During the follow-up period, relapse occurred in 26 (17%) children, and the recurrence rate was highest in the HR group (P<0.05). However, there was no significant difference in the recurrence rate between the SR group and the IR group (P>0.05). The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1 (P<0.01). The predicted 5-year RFS rates in the SR, IR, and HR groups were (94.2±2.9)%, (86.7±3.8)%, and (56.2±4.5)% respectively (P<0.05). The 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 (P<0.01). There was no significant difference in the predicted 5-year RFS rate between the children with functional subtypes of IKZF1 and those with non-functional subtypes of IKZF1 in the SR group (P>0.05). However, the predicted 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 in the IR group and the HR group (P<0.05).
B-ALL children with non-functional subtypes of IKZF1 have a high recurrence rate, and the recurrence rate will be even higher in B-ALL children with non-functional subtypes of IKZF1 and MRD ≥10 on day 33 of chemotherapy.
研究缓解诱导第33天微小残留病(MRD)水平及IKZF1基因型对B系急性淋巴细胞白血病(B-ALL)患儿生存的影响。
本研究纳入152例新诊断的B-ALL患儿,这些患儿在首轮化疗后达到完全缓解且有完整的随访信息。根据缓解诱导第33天通过流式细胞术检测的MRD,将他们分为三组:标准风险(SR)组(MRD<10;n=60)、中风险(IR)组(10≤MRD<10;n=55)和高风险(HR)组(MRD≥10;n=37)。采用巢式逆转录聚合酶链反应(Nested RT-PCR)在化疗前确定所有患儿的IKZF1基因型。分析缓解诱导第33天的MRD水平及IKZF1基因型对B-ALL患儿无复发生存期(RFS)的影响。
152例B-ALL患儿共有7种常见的IKZF1亚型:IK1、IK2/3、IK4、IK6、IK8、IK9和IK10。152例患儿中,130例具有IKZF1功能亚型,22例具有IKZF1无功能亚型。随访期间,26例(17%)患儿复发,HR组复发率最高(P<0.05)。然而,SR组和IR组复发率差异无统计学意义(P>0.05)。IKZF1无功能亚型患儿的累积复发率显著高于IKZF1功能亚型患儿(P<0.01)。SR、IR和HR组预测的5年RFS率分别为(94.2±2.9)%、(86.7±3.8)%和(56.2±4.5)%(P<0.05)。IKZF1功能亚型患儿的5年RFS率显著高于IKZF1无功能亚型患儿(P<0.01)。SR组中IKZF1功能亚型患儿与IKZF1无功能亚型患儿预测的5年RFS率差异无统计学意义(P>0.05)。然而,IR组和HR组中IKZF1功能亚型患儿的预测5年RFS率显著高于IKZF1无功能亚型患儿(P<0.05)。
IKZF1无功能亚型的B-ALL患儿复发率高,化疗第33天IKZF1无功能亚型且MRD≥10的B-ALL患儿复发率更高。