Comparable anti-CMV responses of transplant donor and third-party CMV-specific T cells for treatment of CMV infection after allogeneic stem cell transplantation

Adoptive transfer of cytomegalovirus(CMV)-specific cytotoxic T lymphocytes(CMV-CTLs)from original transplant donors or third-party donors was effective for the treatment of CMV infection after allogenic stem cell transplantation(allo-SCT),but the antiviral activity of CMV-CTL types has not been compared.To determine whether third-party CMV-CTLs provide comparable long-term antiviral efficacy to transplant donor CMV-CTLs,we first compared the antiviral abilities of transplant donors and third-party CMV-CTLs for treatment of CMV infection in two mouse models,compared the in vivo recovery of CMV-specific immunity,and analyzed the underlying mechanisms driving sustained antiviral immunity.The results showed that both donor and third-party CMV-CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days postinfusion.The in vivo recovery of CMV-specific immunity after CMV-CTL infusion was comparable in both groups.A detailed analysis of the source of recovered CMV-CTLs showed the proliferation and expansion of graft-derived endogenous CMV-CTLs in both groups.Our clinical study,which enrolled 31 patients who received third-party CMV-CTLs and 62 matched pairs of individuals who received transplant donor CMV-CTLs for refractory CMV infection,further showed that adoptive therapy with donor or third-party CMV-CTLs had comparable clinical responses without significant therapy-related toxicity.We observed strong expansion of CD8+tetramer+T cells and proliferation of recipient endogenous CMV-CTLs after CMV-CTL infusion,which were associated with a reduced or cleared viral load.Our data confirmed that adoptive therapy with third-party or transplant donor CMV-CTLs triggered comparable antiviral responses to CMV infection that might be mediated by restoration of endogenous CMV-specific immunity.

异基因造血干细胞移植术后侵袭性真菌感染的流行病学:单中心12年研究结果（英文）

目的:回顾性分析了浙江大学医学院附属第一医院骨髓移植中心1998年至2009年接受造血干细胞移植(HSCT)发生侵袭性真菌感染(IFI)的患者资料,评估HSCT后IFI发病情况、流行病学特征及危险因素,以期寻找病原菌特点及相关的危险因素,为制定更有针对性的预防治疗策略提供依据。创新点:首次对本中心异基因HSCT后的IFI感染情况进行统计分析,研究年限长,样本量较大;另作为国内较成熟的移植中心之一,本中心的研究结果对国内异基因HSCT后IFI感染情况有较大的参考意义。方法:对1998年11月至2009年12月在本移植中心接受异基因HSCT的408例患者进行观察分析,总结HSCT后IFI发病情况和病原菌分布,并采用多因素分析判断危险因素。结论:本研究显示IFI与HSCT预后明显相关,HSCT后不同时期IFI病原菌分布及危险因素存在差异。临床应根据IFI病原学特点及HSCT后时间分布特点,采取不同的策略,更有针对性地用药及开始治疗,从而改善预后。