Fukuda Takahiro, Boeckh Michael, Carter Rachel A, Sandmaier Brenda M, Maris Michael B, Maloney David G, Martin Paul J, Storb Rainer F, Marr Kieren A
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Blood. 2003 Aug 1;102(3):827-33. doi: 10.1182/blood-2003-02-0456. Epub 2003 Apr 10.
The incidence of invasive mold infections has increased during the 1990s among patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) after myeloablative conditioning. In this study, we determined risk factors for invasive mold infection and mold infection-related death among 163 patients undergoing allogeneic HCT with nonmyeloablative conditioning. The cumulative incidence rates of proven or probable invasive fungal infections, invasive mold infections, invasive aspergillosis, and invasive candidiasis during the first year after allogeneic HCT with nonmyeloablative conditioning were 19%, 15%, 14%, and 5%, respectively, which were similar to those after conventional myeloablative HCT. Invasive mold infections occurred late after nonmyeloablative conditioning (median, day 107), with primary risk factors including severe acute graft-versus-host disease (GVHD), chronic extensive GVHD, and cytomegalovirus (CMV) disease. The 1-year survival after diagnosis of mold infections was 32%. High-dose corticosteroid therapy at diagnosis of mold infection was associated with an increased risk for mold infection-related death. Overall, nonrelapse mortality was estimated at 22% (36 patients) after nonmyeloablative conditioning, of which 39% (14 patients) were mold infection-related (9% of the overall mortality). More effective strategies are needed to prevent invasive mold infections, which currently account for a notable proportion of nonrelapse mortality after nonmyeloablative allogeneic HCT.
20世纪90年代，在接受清髓性预处理的异基因造血干细胞移植（HCT）患者中，侵袭性霉菌感染的发生率有所上升。在本研究中，我们确定了163例接受非清髓性预处理的异基因HCT患者发生侵袭性霉菌感染及霉菌感染相关死亡的危险因素。接受非清髓性预处理的异基因HCT后第一年，确诊或疑似侵袭性真菌感染、侵袭性霉菌感染、侵袭性曲霉病和侵袭性念珠菌病的累积发生率分别为19%、15%、14%和5%，与传统清髓性HCT后的发生率相似。侵袭性霉菌感染发生在非清髓性预处理后较晚时间（中位时间为第107天），主要危险因素包括严重急性移植物抗宿主病（GVHD）、慢性广泛性GVHD和巨细胞病毒（CMV）疾病。霉菌感染诊断后的1年生存率为32%。霉菌感染诊断时使用大剂量皮质类固醇治疗与霉菌感染相关死亡风险增加有关。总体而言，非清髓性预处理后的非复发死亡率估计为22%（36例患者），其中39%（14例患者）与霉菌感染相关（占总死亡率的9%）。需要更有效的策略来预防侵袭性霉菌感染，目前侵袭性霉菌感染在非清髓性异基因HCT后的非复发死亡率中占相当大的比例。
