儿童混合表型急性白血病29例分析

Diagnosis and treatment efficacy analysis of 29 children with mixed phenotype acute leukemia

目的分析混合表型急性白血病(MPAL)的临床特征及疗效预后。方法回顾性分析2005年1月1日至2019年12月1日就诊于中国医学科学院血液病医院儿童血液病诊疗中心的29例MPAL患儿,分析其形态学、免疫表型、细胞遗传学、分子生物学特点、诱导化疗以及预后情况。应用Kaplan-Meier法绘制生存曲线,单因素分析应用Log-Rank法。结果(1)29例MPAL患儿中1例为MPAL伴KMT2A重排,1例为MPAL伴BCR-ABL1,13例为MPAL伴B-M,12例为MPAL伴T-M,2例为急性未分化细胞白血病。(2)免疫表型阳性率较高的是CD3323例(79%),CD3425例(86%),HLA-DR 20例(69%)。表达CD19的共17例,阳性率59%。(3)8例患儿检测到异常融合基因,其中MLL-AF4基因1例,BCR-ABL1基因1例,TEL-AML1基因3例,WT12例,FLT3-ITD阳性1例。(4)27例获得染色体核型,14例为异常核型,其中10例为复杂核型。(5)接受化疗的27例患儿中完全缓解(CR)率为85%(23/27),5年无病生存率(DFS)为(71±10)%,5年总生存率(OS)为(74±10)%。14例应用急性淋巴细胞白血病(ALL)方案者中13例CR;12例应用联合方案者中10例CR;二者5年OS分别为(77±15)%和(80±13)%,差异无统计学意义(χ²=0.027,P=0.870)。结论MPAL是一种罕见的儿童白血病,易见复杂染色体核型,ALL方案及混合方案诱导缓解化疗可获得较好的预后。

Objective To analyze the clinical characteristics and prognosis of mixed phenotype acute leukemia(MPAL)in children.Methods The data of 29 children diagnosed as MPAL in the Pediatric Blood Disease Center,Institute of Hematology&Blood Disease Hospital,Chinese Academy of Medical Sciences from January 1,2005 to December 1,2019 were collected retrospectively.The morphology,immunophenotypes,cytogenetics,molecular biological characteristics,induction chemotherapy regimen,and prognosis were analyzed.Kaplan-Meier Method was used to draw survival curve.Log-Rank was used for univariate analysis.Results(1)Among 29 MPAL cases,there were 1 case with KMT2A rearrangement,1 case with BCR-ABL1,13 cases with B/myeloid(B-M)type,12 cases with T/myeloid(T-M)type and 2 cases with acute undifferentiated leukemia.(2)The common immunophenotypes were CD33(23 cases,79%),CD34(25 cases,86%)and HLA-DR(20 cases,69%),and CD19 was positive in 17 cases(59%).(3)In molecular genetics analysis,8 cases were detected to have abnormal gene fusion,including 1 case with MLL-AF4 fusion gene,1 case with BCR-ABL1 fusion gene,3 cases with TEL-AML1 fusion gene,2 cases with WT1 and 1 case with FLT3-ITD.(4)In cytogenetics analysis,27 cases obtained chromosome karyotypes,including 14 cases with abnormal karyotypes and 10 cases were complex karyotypes.(5)In treatment efficacy analysis,27 cases received induction chemotherapy and the complete remission(CR)rate was 85%(23/27).The 5-year disease free survival(DFS)rate was(71±10)%and 5-year overall survival(OS)rate was(74±10)%.Thirteen of 14 cases received acute lymphoblastic leukemia(ALL)induction therapy achieved CR,while 10 of 12 cases received hybrid induction therapy achieved CR.No significant difference was found in 5 year-OS rates between cases with ALL induction therapy and hybrid induction therapy((77±15)%vs.(80±13)%,χ^²=0.027,P=0.870).Conclusions MPAL is a rare childhood leukemia and is prone to incorporate complex karyotypes.Induction therapy with ALL or hybrid regimens is a good choice to obtain favorable prognosis.