TET2基因突变对儿童骨髓增生异常综合征疗效的影响

Effect of TET2 gene mutation on the curative efficacy of myelodysplastic syndromes in children

目的探讨低剂量亚砷酸/维A酸联合或不联合低剂量阿糖胞苷诱导方案治疗TET2基因突变儿童骨髓增生异常综合征(MDS)的疗效。方法选择2009年3月至2018年4月哈尔滨市第一医院血液病肿瘤研究所住院MDS患儿9例,其中儿童难治性血细胞减少(RCC)3例,MDS伴原始细胞增多Ⅰ型(MDS-EBⅠ)4例,MDS伴原始细胞增多Ⅱ型(MDS-EBⅡ)2例。应用二代基因测序法(NGS)检测MDS患儿骨髓细胞TET2基因突变。采用低剂量亚砷酸/维A酸联合或不联合阿糖胞苷诱导方案分层治疗儿童MDS。临床疗效评价参照2006年MDS国际工作组(IWG)制定的MDS疗效评价标准。结果9例患儿中,近期临床有效8例。TET2基因突变阳性2例,均获得了骨髓完全缓解(mCR)并血液学改善(HI)的近期临床疗效;7例TET2基因突变阴性患儿近期临床疗效为CR 4例,mCR并HI 1例,疾病稳定(SD)1例。结论低剂量亚砷酸/维A酸联合或不联合低剂量阿糖胞苷方案可能使TET2基因突变阳性儿童MDS受益。

Objective To explore the therapeutic effect of low-dose arsenous acid/tretinoin with or without low-dose cytarabine induction regimen on myelodysplastic syndromes(MDS)with TET2 gene mutation in children.Methods Nine children with MDS who were hospitalized at the First Hospital of Harbin from March 2009 to April 2018 were collected,including 3 cases of refractory cytopenia of childhood(RCC),4 cases of MDS with excess of blasts typeⅠ(MDS-EBⅠ)and 2 cases of MDS with excess of blasts typeⅡ(MDS-EBⅡ).The next-generation gene sequencing method(NGS)was applied to detect the TET2 gene mutation in bone marrow cells of children with MDS.The low-dose arsenous acid/tretinoin with or without low-dose cytarabine induction regimen was adopted to conduct tiered therapy on children with MDS.The clinical efficacy was assessed in line with the MDS response evaluation criteria adopted by the MDS International Working Group(IWG)in 2006.Results Among the 9 patients,the short-term clinical efficacy was observed in 8 cases.Two patients with TET2 gene mutation achieved the short-term clinical efficacy of bone marrow complete remission(mCR)and hematological improvement(HI).Among 7 patients without TET2 gene mutation,4 patients obtained CR,1 patients obtained mCR and HI,and 1 patients obtained stable disease(SD)in terms of the short-term clinical efficacy.Conclusion The low-dose arsenous acid/tretinoin with or without low-dose cytarabine regimen may be beneficial to MDS children with TET2 gene mutation.