Battiwalla Minoo, Wu Yiyuan, Bajwa Rajinder P S, Radovic Marija, Almyroudis Nikolaos G, Segal Brahm H, Wallace Paul K, Nakamura Ryotaro, Padmanabhan Swaminathan, Hahn Theresa, McCarthy Philip L
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14202, USA.
Biol Blood Marrow Transplant. 2007 Jul;13(7):765-70. doi: 10.1016/j.bbmt.2007.03.009. Epub 2007 May 7.
Cytomegalovirus (CMV) disease-related mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients has dramatically declined because of ganciclovir prophylaxis and preemptive therapeutic strategies. However, ganciclovir has not improved overall survival in randomized studies despite effectively preventing overt CMV disease. Moreover, recurrent posttransplant CMV antigenemia, associated with prolonged ganciclovir exposure, is a predictor of increased relapse of malignancy. We examined the hypothesis that ganciclovir itself may have a negative impact on immune reconstitution by testing the effect of ganciclovir on normal human lymphocytes in vitro. T-lymphocyte activation and proliferation, as measured by PHA-induced (3)H-thymidine uptake, was greatly reduced at therapeutic concentrations of ganciclovir (10 microg/mL) but not for foscarnet (300 microM/L). Moreover, ganciclovir impaired bromodeoxyuridine incorporation in proliferating lymphocytes, but did not impair lymphocyte survival or induce lymphocyte apoptosis. Collectively, these results show that ganciclovir suppresses T-lymphocyte proliferation in vitro by inhibiting DNA synthesis; with implications for T-lymphocyte function following allogeneic BMT.
由于使用更昔洛韦进行预防和抢先治疗策略，异基因造血干细胞移植（HSCT）受者中与巨细胞病毒（CMV）疾病相关的死亡率已大幅下降。然而，尽管更昔洛韦能有效预防明显的CMV疾病，但在随机研究中它并未提高总体生存率。此外，与更昔洛韦长期暴露相关的移植后CMV抗原血症复发，是恶性肿瘤复发增加的一个预测指标。我们通过在体外测试更昔洛韦对正常人淋巴细胞的作用，来检验更昔洛韦本身可能对免疫重建产生负面影响这一假设。用PHA诱导的（3）H-胸腺嘧啶核苷摄取来衡量，在更昔洛韦治疗浓度（10微克/毫升）下，T淋巴细胞的活化和增殖大幅降低，但膦甲酸钠（300微摩尔/升）则不会。此外，更昔洛韦会损害增殖淋巴细胞中溴脱氧尿苷的掺入，但不会损害淋巴细胞存活或诱导淋巴细胞凋亡。总体而言，这些结果表明，更昔洛韦在体外通过抑制DNA合成来抑制T淋巴细胞增殖；这对异基因骨髓移植后的T淋巴细胞功能有影响。
