进展期骨髓增生异常综合征患儿的临床特征及预后的影响因素

Clinical features and prognostic factors of advanced myelodysplastic syndromes in children

目的探讨进展期骨髓增生异常综合征(MDS)患儿的临床特征及预后的影响因素。方法回顾性纳入中国医学科学院血液病医院2009年9月至2022年4月诊断为进展期MDS患儿的临床资料,通过电话、查阅病历资料进行随访,随访至2023年5月1日,通过分析染色体核型检测、基因二代测序结果,总结进展期MDS患儿的临床特征;应用多因素Cox回归分析探讨进展期MDS患儿预后的影响因素。结果共纳入69例患儿,男49例,女20例,年龄[M(Q_(1),Q_(3))]为8(5,10)岁。67例进行染色体核型检测,42例(62.7%)患儿核型异常,其中7号染色体单体最为常见,有17例(25.4%);43例行二代测序检查,以SETBP1、NRAS、PTPN11、RUNX1基因突变较为常见,分别有12例(27.9%)、9例(20.9%)、8例(18.6%)、8例(18.6%)。随访时间[M(Q_(1),Q_(3))]为26(13,56)个月,5年总生存率为56%(95%CI:44.4%~70.5%)。接受造血干细胞移植(HSCT)患儿的5年总生存率高于未接受HSCT的患儿(73.9%比29.1%,P<0.001)。HSCT(HR=0.118,95%CI:0.037~0.372,P<0.001)是进展期MDS患儿总生存率的保护因素;诊断时铁蛋白水平(>356.3μg/L)(HR=6.497,95%CI:2.068~20.415,P=0.001)以及脾脏中、重度肿大(HR=4.075,95%CI:1.174~14.141,P=0.027)是进展期MDS患儿总生存率的危险因素。结论进展期MDS患儿最常见的异常染色体核型和突变基因分别是7号染色单体和SETBP1基因。HSCT、铁蛋白增高和脾中、重度肿大是进展期MDS患儿总生存率的影响因素。

Objective To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes(MDS)in children.Methods Clinical data of children diagnosed with advanced MDS in the Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences,between September 2009 and April 2022 were retrospectively collected.Follow-up assessments were performed through telephone interviews and the review of medical records until May 1,2023.The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests,second-generation gene sequencing results.Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children.Results A total of 69 children,comprising 49 males and 20 females,aged[M(Q_(1),Q_(3))]8(5,10)years,were enrolled in the study.Sixty-seven cases underwent chromosomal karyotype testing,of which 42 cases(62.7%)had abnormal karyotypes,with monosomy 7 the most common in 17 cases(25.4%).Forty-three cases underwent next-generation sequencing,with mutations in the SETBP1,NRAS,PTPN11 and RUNX1 genes more common,identified in 12 cases(27.9%),9 cases(20.9%),8 cases(18.6%),and 8 cases(18.6%),respectively.The follow-up time[M(Q_(1),Q_(3))]was 26(13,56)months and the 5-year overall survival rate was 56%(95%CI:44.4%-70.5%).The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation(HSCT)was higher than that of children who did not undergo HSCT(73.9%vs 29.1%,P<0.001).HSCT(HR=0.118,95%CI:0.037-0.372,P<0.001)was a protective factor for the overall survival rate of children with advanced MDS.Serum ferritin level>356.3μg/L(HR=6.497,95%CI:2.068-20.415,P=0.001)and moderate to severe splenomegaly(HR=4.075,95%CI:1.174-14.141,P=0.027)were risk factors for the overall survival rate of children with advanced MDS.Conclusions Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS.HSCT,increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.