van Burik Jo-Anne H, Carter Shelly L, Freifeld Alison G, High Kevin P, Godder Kamar T, Papanicolaou Genovefa A, Mendizabal Adam M, Wagner John E, Yanovich Saul, Kernan Nancy A
Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Biol Blood Marrow Transplant. 2007 Dec;13(12):1487-98. doi: 10.1016/j.bbmt.2007.08.049.
Serious infections are a major obstacle limiting the usefulness of unrelated donor marrow transplantation. Graft-versus-host disease (GVHD) and its therapy are associated with a high risk of opportunistic infection. In this study, patients were randomized to receive 1 of 2 GVHD prophylaxis strategies, marrow T cell depletion, and cyclosporine (TCD) or methotrexate/cyclosporine (M/C) after transplantation. The patients underwent transplantation between March 1995 and October 2000 as part of a multicenter randomized trial. As a secondary analysis, we analyzed infections in this study cohort. Among the 404 patients who underwent transplantation, a total of 1598 infections were reported. The rates of serious and fatal infections did not differ between the TCD and M/C groups. Bacterial infections accounted for 1/3 of serious infections in each treatment arm. A significantly higher incidence of severe cytomegalovirus (CMV) and life-threatening or fatal aspergillus infections was observed in the patients receiving TCD (CMV, 28% vs 17% [P = .02]; aspergillosis, 16% vs 7% [P < .01]). The only independent risk factor for serious infection was the development of grade III-IV acute GVHD (aGVHD; hazard ratio = 1.41; 95% confidence interval = 1.03-1.91). Strategies to speed immune recovery, even in the absence of GVHD, are needed to overcome the risk of infection after unrelated donor transplantation.
严重感染是限制无关供者骨髓移植效用的主要障碍。移植物抗宿主病(GVHD)及其治疗与机会性感染的高风险相关。在本研究中,患者被随机分配接受两种GVHD预防策略中的一种,即移植后进行骨髓T细胞清除并使用环孢素(TCD),或使用甲氨蝶呤/环孢素(M/C)。作为一项多中心随机试验的一部分,这些患者于1995年3月至2000年10月期间接受了移植。作为一项次要分析,我们分析了该研究队列中的感染情况。在接受移植的404例患者中,共报告了1598例感染。TCD组和M/C组的严重和致命感染发生率没有差异。细菌感染在每个治疗组的严重感染中占三分之一。在接受TCD的患者中,观察到严重巨细胞病毒(CMV)感染以及危及生命或致命的曲霉感染的发生率显著更高(CMV,28%对17%[P = .02];曲霉病,16%对7%[P < .01])。严重感染的唯一独立危险因素是III-IV级急性GVHD(aGVHD)的发生(风险比 = 1.41;95%置信区间 = 1.03 - 1.91)。即使在没有GVHD的情况下,也需要采取加速免疫恢复的策略来克服无关供者移植后感染的风险。