Bilgrami S, Chakraborty N G, Rodriguez-Pinero F, Khan A M, Feingold J M, Bona R D, Edwards R L, Dorsky D, Clive J, Mukherji B, Tutschka P J
Bone Marrow Transplant Program, University of Connecticut Health Center, Farmington 06030, USA.
Bone Marrow Transplant. 1999 Mar;23(5):469-74. doi: 10.1038/sj.bmt.1701594.
A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.
对215例连续接受大剂量化疗（HDC）及自体干细胞救援（ASCR）的患者进行回顾性评估，以确定水痘带状疱疹病毒（VZV）感染的发生率、时间进程及转归。40例患者在ASCR后中位时间69天被诊断为带状疱疹。其中6例发生在ASCR前中位时间33天，但在开始大剂量干细胞动员化疗之后。25%的患者出现皮肤或全身播散，32.5%的患者因疱疹后神经痛需要医学干预。除2例患者外，所有患者均接受了抗病毒化疗。1例活动性VZV感染患者在ASCR后39天死于多器官功能衰竭。多因素风险分析显示，单纯疱疹病毒血清学阳性个体使用预防性阿昔洛韦可降低VZV感染风险。此外，使用白消安、噻替派和卡铂作为预处理化疗方案与后续VZV感染风险增加相关。HDC及ASCR后VZV再激活的发生率与骨髓移植后观察到的相似，但发病更早。这可能与ASCR前给予的干细胞动员化疗更早诱导免疫抑制有关。我们发现干细胞动员化疗前后获取的外周血单个核细胞的增殖及合成能力显著降低。此外，超过80%的VZV感染发生在ASCR后6个月内，与异基因及自体骨髓移植相比，晚期病例很少见。在HDC-ASCR背景下，最大免疫抑制期抗病毒化学预防的作用需要进一步研究。
