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儿童造血干细胞移植后水痘带状疱疹病毒再激活与白血病治疗及宿主T淋巴细胞免疫抑制密切相关。

Varicella zoster reactivation after hematopoietic stem cell transplant in children is strongly correlated with leukemia treatment and suppression of host T-lymphocyte immunity.

作者信息

Vermont C L, Jol-van der Zijde E C M, Hissink Muller P, Ball L M, Bredius R G M, Vossen A C, Lankester A C

机构信息

Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Transpl Infect Dis. 2014 Apr;16(2):188-94. doi: 10.1111/tid.12180. Epub 2014 Jan 20.

DOI:10.1111/tid.12180
PMID:24438482
Abstract

BACKGROUND AND AIMS

Varicella zoster virus (VZV) reactivation following hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality. We undertook a retrospective study to determine the frequency and risk factors associated with VZV reactivation, including underlying disease, the use of fludarabine in high-risk leukemia chemotherapy protocols, and immune status before HSCT.

PATIENTS AND METHODS

We studied 163 children who underwent a first HSCT between 2002 and 2008, before introduction of routine VZV prophylaxis on our unit. VZV diagnosis was based on clinical features and supported by polymerase chain reaction on plasma and/or vesical fluid. Patient data and possible risk factors pre- and post HSCT were recorded and compared using a multivariate regression analysis.

RESULTS

Within this cohort, 41 (25%) patients developed VZV reactivation during the first year after transplantation at a median of 60 days post HSCT. VZV reactivation occurred more often within the subgroup of patients with acute leukemia compared with the remainder of patients (38% vs. 15%, P < 0.01). Multivariate Cox regression analysis revealed that, besides positive VZV serology in patients pre-HSCT (P = 0.03), acute leukemia as the indication for HSCT remained the only independent risk factor for VZV reactivation (P = 0.025, odds ratio 2.5, 95% confidence interval 1.1-5.6). This was associated with low pre-transplant T-cell counts, especially in the CD4(+) subset. No differences were found in relation to donor type, age, or use of serotherapy.

CONCLUSION

VZV reactivation after HSCT predominates in acute leukemia patients and is associated with low T CD4(+) lymphocyte counts. This finding demonstrates the impact of pre-HSCT host immune suppression on VZV reactivation patterns after HSCT.

摘要

背景与目的

造血干细胞移植(HSCT)后水痘带状疱疹病毒(VZV)再激活可能导致显著的发病率和死亡率。我们进行了一项回顾性研究,以确定与VZV再激活相关的频率和风险因素,包括基础疾病、高危白血病化疗方案中氟达拉滨的使用以及HSCT前的免疫状态。

患者与方法

我们研究了2002年至2008年期间在我们科室引入常规VZV预防措施之前接受首次HSCT的163名儿童。VZV诊断基于临床特征,并通过血浆和/或水疱液的聚合酶链反应得到支持。记录患者数据以及HSCT前后可能的风险因素,并使用多变量回归分析进行比较。

结果

在该队列中,41名(25%)患者在移植后的第一年发生了VZV再激活,中位时间为HSCT后60天。与其余患者相比,急性白血病患者亚组中VZV再激活更为常见(38%对15%,P<0.01)。多变量Cox回归分析显示,除了HSCT前患者VZV血清学阳性(P=0.03)外,作为HSCT指征的急性白血病仍然是VZV再激活的唯一独立风险因素(P=0.025,比值比2.5,95%置信区间1.1-5.6)。这与移植前T细胞计数低有关,尤其是在CD4(+)亚群中。在供体类型、年龄或血清疗法的使用方面未发现差异。

结论

HSCT后VZV再激活在急性白血病患者中占主导地位,并且与低CD4(+)淋巴细胞计数有关。这一发现证明了HSCT前宿主免疫抑制对HSCT后VZV再激活模式的影响。

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