Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation
Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation
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DOI：
10.1182/blood-2002-11-3472
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发表时间：
2003-10-15
期刊：
影响因子：
20.3
通讯作者：
Boeckh, M
中科院分区：
文献类型：
--
作者：
Hakki, M;Riddell, SR;Boeckh, M
造血干细胞移植（HSCT）后3个月细胞免疫的重建是移植长期成功的关键决定因素。我们通过单因素和多因素分析，分析了影响HSCT后3个月巨细胞病毒（CMV）特异性CD 4（+）和CD 8（+）功能恢复的因素，包括干细胞来源（骨髓与外周血干细胞[PBSC]）、年龄、性别、移植物抗宿主病（GVHD）、类固醇使用、预处理方案、更昔洛韦使用、HILA匹配、循环巨细胞病毒抗原血症，绝对CD 4（+）和CD 8（+）计数和供体CMV血清学。在多变量分析中，高剂量类固醇和CD 4（+）计数低于100 × 10（9）/L是CD 4（+）功能恢复受损的重要预测因素。在多变量分析中，高剂量类固醇、骨髓作为干细胞来源和CD 8（+）计数低于50 × 10（9）/L与CD 8（+）功能受损相关。发现类固醇以剂量依赖性方式损害CD 4（+）和CD 8（+）功能。在没有大剂量类固醇的情况下，低水平亚临床CMV抗原血症被发现刺激更昔洛韦预防接受者的CD 4（+）和CD 8（+）功能恢复。在接受更昔洛韦预防性治疗和抗原血症引导的预防性治疗的患者之间，免疫重建没有差异。因此，CD 4（+）和CD 8（+）绝对计数分别低于100 × 10（9）/L和50 × 10（9）/L;骨髓作为干细胞来源;以及高剂量类固醇的使用都预示着移植后3个月功能性T细胞免疫恢复延迟。亚临床CMV再激活，而更昔洛韦似乎是一个有效的刺激T细胞功能。这些发现对这一人群的疫苗接种和过继免疫治疗策略具有重要意义。（血。2003; 102：3060-3067）。(C)2003年，美国血液学会。
Reconstitution of cellular immunity by 3 months after hematopoietic stem cell transplantation (HSCT) is a critical determinant of the long-term success of the transplantation. We analyzed the factors affecting recovery of cytomegalovirus (CMV)-specific CD4(+) and CD8(+) function at 3 months after HSCT by univariate and multivariable analyses including source of stem cells (bone marrow vs peripheral blood stem cells [PBSCs]), age, sex, graft-versus-host disease (GVHD), steroid use, conditioning regimens, ganciclovir use, HILA matching, circulating CMV antigenemia, absolute CD4(+) and CD8(+) counts, and donor CMV serology. High-dose steroids and CD4(+) count less than 100 x 10(9)/L were significant predictors of impaired CD4(+) functional recovery in the multivariable analysis. High-dose steroids, bone marrow as a source of stem cells, and CD8(+) count less than 50 x 10(9)/L were associated with impaired CD8(+) function in the multivariable analysis. Steroids were found to impair both CD4(+) and CD8(+) function in a dose-dependent manner. In the absence of high-dose steroids, low-level subclinical CMV antigenemia was found to stimulate both CD4(+) and CD8(+) functional recovery in recipients of ganciclovir prophylaxis. There was no difference in immune reconstitution between those who received prophylactic ganciclovir versus antigenemia-guided pre-emptive therapy. Thus, absolute CD4(+) and CD8(+) counts less than 100 x 10(9)/L and 50 x 10(9)/L, respectively; bone marrow as the source of stem cells; and high-dose steroid use all predict delayed recovery of functional T-cell immunity at 3 months after transplantation. Subclinical CMV reactivation while on ganciclovir appears to be a potent stimulator of T-cell function. These findings have implications for vaccination and adoptive-immunotherapy strategies in this population. (Blood. 2003; 102:3060-3067). (C) 2003 by The American Society of Hematology.