摘要
目的评价异基因造血干细胞移植(allo-HSCT)治疗儿童EB病毒(EBV)阳性淋巴组织增殖性疾病(EBV+LPD)的疗效。方法回顾性分析2019年7月至2022年7月郑州大学附属儿童医院收治的9例行allo-HSCT的EBV+LPD患儿的临床特征、治疗及预后情况。结果9例患儿均行组织病理学检查,其中儿童EBV阳性T淋巴组织增殖性疾病(EBV+T-LPD)6例、肺淋巴瘤样肉芽肿1例、儿童系统性EBV阳性T细胞淋巴瘤2例。男6例,女3例,中位年龄5.8(1.5~13.0)岁。初诊时血浆EBV-DNA拷贝数为(5.67~865.00)×10^(2)/mL,外周血细胞EBV-DNA拷贝数为(5.13~1250.00)×10^(2)/mL,3例脑脊液EBV-DNA升高,拷贝数为(5.18~291.00)×10^(2)/mL。全外显子测序:3例未见异常,1例肺淋巴瘤样肉芽肿伴IL2RG突变、1例EBV+T-LPD发现SH2D1A基因有1个半合子突变,为致病性变异;其他4例发现基因突变均为非致病性变异。9例患儿移植前病程5.4(3.0~10.0)个月;移植前疾病状态:3例淋巴瘤均部分缓解,6例EBV+T-LPD中2例疾病活动,4例疾病无活动。供者中亲缘半相合5例,同胞全相合、无关全相合各2例。回输外周血和/或骨髓造血干细胞单个核细胞计数中位数为6.60(3.64~12.18)×10^(8)/kg,中性粒细胞中位植入时间18(9~23)d。回输造血干细胞起1个月后患儿血浆中EBV-DNA定量均转阴性,7例外周血EBV-DNA定量阴性、2例拷贝数102/mL;3个月评估患儿血浆及外周血EBV-DNA定量均阴性,3例淋巴瘤影像学完全缓解,6例EBV+T-LPD疾病无活动。所有移植相关并发症经药物治疗后均有效控制。截至2023年2月,中位随访时间24(11~42)个月,患儿均无病生存,无因移植物抗宿主病严重影响生活质量病例。结论allo-HSCT治疗儿童EBV+LPD疗效显著,移植相关并发症可控,移植后患儿可获得长期无病生存。
ObjectiveTo evaluate the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV+LPD).MethodsThe clinical features,treatment course,and prognosis of 9 children with EBV+LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively.ResultsAll the 9 children underwent histopathological examination,including 6 patients with EBV-positive T-cell lymphoproliferative disease(EBV+T-LPD),1 with pulmonary lymphomatoid granuloma,and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females,with the median age of 5.8(1.5-13.0)years.At the initial diagnosis,plasma and peripheral EBV-DNA copy at the initial diagnosis was(5.67-865.00)×10^(2)/mL,and(5.13-1250.00)×10^(2)/mL,respectively.The EBV-DNA load of cerebrospinal fluid increased to(5.18-291.00)×10^(2)/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases,pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV+T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0)months.Disease status before transplantation was as follows:all 3 cases of lymphomas had partial regression;2 cases of EBV+T-LPD had active disease;and 4 cases had no active disease.Among the donors,there were 5 cases of half-matched relatives,2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10^(8)/kg,while the median implantation time of neutrophils was 18(9-23)days.One month after the transfusion of hematopoietic stem cells,plasma EBV-DNA copy was negative in all cases,and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was
作者
周建文
何永艳
马平
张卫芳
王亚峰
刘炜
周强
毛彦娜
Zhou Jianwen;He Yongyan;Ma Ping;Zhang Weifang;Wang Yafeng;Liu Wei;Zhou Qiang;Mao Yanna(Department of Hematology and Oncology,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou 450018,China;Department of Pathology,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou 450018,China)
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2023年第12期932-936,共5页
Chinese Journal of Applied Clinical Pediatrics
基金
河南省科技攻关计划项目(212102310036)。
关键词
儿童
联合化疗
EB病毒阳性淋巴组织增殖性疾病
肺淋巴瘤样肉芽肿
系统性EB病毒阳性T细胞淋巴瘤
异基因造血干细胞移植
Child
Combined chemotherapy
Epstein-Barr virus-positive lymphoproliferative disease
Pulmonary lymphomatoid granulomatosis
Systemic Epstein-Barr virus-positive T-cell lymphoma
Allogeneic hematopoietic stem cell transplantation
