幼年型粒单核细胞白血病19例病例系列报告

19 cases of juvenile myelomonocytic leukemia:A case series report

目的探讨幼年型粒单核细胞白血病(JMML)患儿的临床特征及基因突变情况。方法回顾性分析2013年1月至2019年12月在郑州大学第一附属医院儿科血液肿瘤科确诊JMML的患儿的临床资料。结果19例JMML患儿中,男14例,女5例。就诊时年龄为(16.8±16.4)个月,>2岁5例。就诊时最常见的症状为发热和皮肤苍白。19例均有肝脾肿大,肝、脾肋缘下最大分别达12 cm和13 cm。淋巴结肿大11例,常见部位为颈部和腋下。外周血WBC、单核细胞和PLT中位数分别为37.3×10^9·L^-1、7.2×10^9·L^-1和32×10^9·L^-1。12例检测了血红蛋白电泳(HbF),4例HbF高于正常。12例检测病毒IgM阳性,以CMV最多(8例)。15例患儿骨髓中原始粒细胞百分比中位值为1.2%(0~6.4%)。7例行染色体核型分析,2例发现7号染色体单体。15例患儿行BCR/ABL1融合基因检测,均为阴性。7例行JMML相关基因突变检测,KRAS、NF1和NRAS基因突变分别为4、2和1例。14例放弃治疗,5例进行随访,截止至2020年6月1日,3例死亡,2例存活,中位生存时间为2(1~34)个月。2例存活患儿中,1例给予化疗并等待造血干细胞移植,另1例转变为急性髓系白血病,按急性髓系白血病治疗方案化疗。3例死亡病例均未行化疗,存活时间为1~2个月。结论本文JMML患儿中以KRAS基因突变常见;未行治疗的JMML患儿生存期较短。

Objective To analyze the clinical characteristics and gene mutations of juvenile myelomonocytic leukemia(JMML).Methods The clinical data of children diagnosed with JMML from January 2013 to December 2019 in the Department of Pediatric Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results Among the 19 children with JMML,there were 14 males and 5 females.The age at the time of visit was(16.8±16.4)months old,and 5 patients were older than 2 years old.The most common symptoms at the time of the visit were fever and pale skin.All 19 cases had hepatosplenomegaly,with the maximum of 12 cm and 13 cm under the costal margin of the liver and spleen,respectively.Lymphadenopathy was found in 11 cases,and the common sites were neck and axilla.The WBC,monocyte and PLT in peripheral blood were 37.3×10^9·L^-1,7.2×10^9·L^-1 and 32×10^9·L^-1,respectively.Four children had higher hemoglobin F(HbF)level than normal.Viral IgM was positive in 12 cases,with CMV being the most common(8 cases).The median percentage of primordial granulocytes in the bone marrow of 15 children was 1.2%(0-6.4%).Chromosome karyotype analysis was performed in 7 cases,and chromosome 7 monosomy was found in 2 cases.The BCR/ABL1 fusion gene test was negative in 15 children.The number of patients with KRAS,NF1 and NRAS gene mutations was 4,2 and 1,respectively.Fourteen cases gave up treatment.Five patients were followed up,and as of June 1,2020,three died and two survived,with a median survival time of 2(1-34)months.Of the two surviving children,one was treated with chemotherapy and awaited hematopoietic stem cell transplantation,and the other one was transformed into acute myeloid leukemia M5,which was treated with chemotherapy according to the treatment regimen of acute myeloid leukemia.None of the 3 deaths was treated with chemotherapy,and the survival time was 1 to 2 months.Conclusion In this study,KRAS gene mutations were common in JMML children.Children with untreated JMML had shorter survival time.