Objective: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL).
Methods: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment.
Results: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×109/L, the median hemoglobin was 67 g/L and median platelet was 16×109/L. An increase of primitive and naive megakaryocytes was found in the bone marrow sample. The immunophenotypes of bone marrow detected by flow cytometry in 19 children were all positive expressed for CD41, CD61. Genetic tests showed that five cases carrying EVI1, including one complicating with MLL/AF10, one patient carrying HOX11, one carrying GATA1, IKZF1 and DDX11 mutations, one patient carrying missense mutation of NRAS, one with missense mutation of KRAS and two cases with high expression of WT1. Karyotype analysis were performed in 11 cases of children, including four with normal karyotype, four with complex karyotypes, one with trisomy 8, one with 7/13 trisomy 21 without Down syndrome manifestations (considered as abnormal somatic karyotype) and one Robertsonian translocation carrier involving chromosomes 14 and 21. Ten children received treatment, including three cases with allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR), two cases with complete donor implantation, and one without implanted but hematopoietic recovered, these three children were followed up for 26, 15 and 12 months respectively and the minimal residual disease (MRD) were all less than 10-4. Another three cases achieving CR after chemotherapy but relapsed in 5, 10 and 12 months after the onset respectively, and all the three children were died eventually. One children died of pulmonary hemorrhage during chemotherapy and three children died from discontinuation of treatment after non remission. The remaining nine children died because of without chemotherapy treatment.
Conclusion: Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.
题目: 儿童non-DS-AMKL的临床特点及预后分析.
目的: 分析儿童非Down综合征相关急性巨核细胞白血病（non-DS-AMKL）的临床特征及治疗效果.
方法: 对2008年5月至2018年4月中山大学孙逸仙纪念医院儿科血液病区收治的19例non-DS-AMKL患儿的临床资料进行回顾性分析，总结其发病特点、实验室检查结果及治疗方法，并对所有患儿进行随访，统计治疗效果.
结果: 19例non-DS-AMKL患儿，其中男9例，女10例，发病中位年龄为2岁。临床表现无特异性。外周血白细胞中位数15.88×109/L，血红蛋白中位数67 g/L，血小板中位数16×109/L。骨髓象见原始和幼稚巨核细胞增多。19例患儿骨髓流式细胞术检测免疫表型均表达CD41、CD61。基因检测结果中，5例EVI1+，其中1例合并MLL/AF10+，1例HOX11+，1例存在GATA1、IKZF1、DDX11基因变异，2例NRAS错义变异，1例KRAS错义变异，2例WT1高表达。11例行染色体核型分析，其中4例染色体正常，4例为复杂核型，1例为8三体， 1例7/13个细胞核型为21三体但无Down综合征临床表现（考虑为体细胞核型异常），1例为14号和21号染色体罗伯特易位携带者。10例患儿接受治疗，有6例患儿获得完全缓解（CR），其中3例CR后接受异基因造血干细胞移植术，2例完全供体植入，1例未植入但自身造血恢复，分别随访26、15及12个月，微小残留病灶监测（MRD）均＜10-4；另外3例CR患儿分别于发病5、10和12个月复发，最终均未能再次达到CR而死亡。1例化疗中因肺出血死亡，另外3例中途放弃化疗最终死亡，其余9例患儿均未接受化疗最终死亡.
结论: 儿童non-DS-AMKL较为少见，临床诊断困难，尽早明确MICM分型有助于确诊，基因检测对于明确诊断和评估预后有重要意义。化疗后获得CR的患者，尽早行造血干细胞移植术可能是治愈AMKL的有效手段.