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儿童异基因造血干细胞移植中与爱泼斯坦-巴尔病毒相关的移植后淋巴细胞增生性疾病前瞻性预防方案:病毒学监测及一线治疗

Prospective Epstein-Barr virus-related post-transplant lymphoproliferative disorder prevention program in pediatric allogeneic hematopoietic stem cell transplant: virological monitoring and first-line treatment.

作者信息

Chiereghin A, Prete A, Belotti T, Gibertoni D, Piccirilli G, Gabrielli L, Pession A, Lazzarotto T

机构信息

Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Bologna, Italy.

Pediatric Oncology and Haematology Unit "Lalla Seràgnoli", Department of Pediatrics, St. Orsola-Malpighi University Hospital, Bologna, Italy.

出版信息

Transpl Infect Dis. 2016 Feb;18(1):44-54. doi: 10.1111/tid.12485. Epub 2016 Jan 30.

Abstract

BACKGROUND

In 28 pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, we aimed to evaluate: (i) the impact of routine Epstein-Barr virus (EBV) DNA monitoring on the development of EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD); (ii) the incidence of EBV infection and the potential risk factors; and (iii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV-PTLD.

METHODS

Quantitative real-time polymerase chain reaction assay was performed on WB samples for all patients. EBV DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for the patients at higher risk of developing EBV-PTLD (≥ 10,000 copies/mL WB).

RESULTS

High EBV DNAemia levels were observed in 37.5% of the actively infected recipients (57.1%). Severe aplastic anemia, matched-unrelated donor transplant, the reduced-intensity conditioning regimen and, to a lesser extent, the in vivo T-cell depletion with anti-thymocyte immunoglobulin were associated with high viral load. A significant correlation between EBV DNA levels in WB and PBMC samples was obtained (r = 0.755, P < 0.001). A similar kinetics of EBV DNA in the 2 blood compartments was observed. Clinically, both specimen types appeared to be equally informative to assess the risk of patients to develop PTLD. On the basis of EBV DNAemia levels, in 3 patients (10.7%) immunosuppressive therapy was reduced and 1 patient (3.5%) received early treatment for probable EBV disease. No patients developed EBV-PTLD.

CONCLUSION

WB proved to be a suitable clinical specimen to monitor EBV DNA load after allo-HSCT for the management of EBV infection and PTLD prevention.

摘要

背景

在28例儿科异基因造血干细胞移植(allo-HSCT)受者中,我们旨在评估:(i)常规监测爱泼斯坦-巴尔病毒(EBV)DNA对EBV相关移植后淋巴细胞增殖性疾病(EBV-PTLD)发生的影响;(ii)EBV感染的发生率及潜在危险因素;(iii)全血(WB)作为监测患者发生EBV-PTLD风险的临床标本的适用性。

方法

对所有患者的WB样本进行定量实时聚合酶链反应检测。对于发生EBV-PTLD风险较高(WB≥10,000拷贝/mL)的患者,也采用外周血单个核细胞(PBMCs)样本进行EBV DNA定量检测。

结果

在37.5%的活动性感染受者中观察到高EBV血症水平(57.1%)。严重再生障碍性贫血、匹配无关供者移植、减低强度预处理方案以及在较小程度上使用抗胸腺细胞免疫球蛋白进行体内T细胞清除与高病毒载量相关。WB和PBMC样本中的EBV DNA水平之间存在显著相关性(r = 0.755,P < 0.001)。在两个血液成分中观察到EBV DNA具有相似的动力学变化。临床上,两种样本类型在评估患者发生PTLD的风险方面似乎同样具有参考价值。根据EBV血症水平,3例患者(10.7%)减少了免疫抑制治疗,1例患者(3.5%)因可能的EBV疾病接受了早期治疗。没有患者发生EBV-PTLD。

结论

对于allo-HSCT后EBV感染的管理和PTLD的预防,WB被证明是一种适合监测EBV DNA载量的临床标本。

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