Sun Yuqian, Meng Fanyi, Han Mingzhe, Zhang Xi, Yu Li, Huang He, Wu Depei, Ren Hanyun, Wang Chun, Shen Zhixiang, Ji Yu, Huang Xiaojun
Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
Nanfang Hospital, Nanfang Medical University, Guangzhou, China.
Biol Blood Marrow Transplant. 2015 Jun;21(6):1117-26. doi: 10.1016/j.bbmt.2015.03.018. Epub 2015 Mar 31.
The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm(3) for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather than autologous (17 of 348; 4.9%) HSCT and was significantly higher in patients receiving pre-emptive (18.6%) rather than empirical (6.1%) or targeted (9.5%) antifungal therapy (P = .002). Improvements in the selection and timing of prophylactic antifungals would be welcome. Health care providers should remain alert to the increased risk of IFD and associated mortality in allogeneic HSCT recipients and the ongoing risk of IFD even after discharge from the hospital.
中国血液病抗真菌治疗评估研究是中国首个关于侵袭性真菌病（IFD）的大规模观察性研究，该研究在中国31家医院纳入了1401例接受造血干细胞移植（HSCT）的患者（75.2%为异基因移植，24.8%为自体移植）。确诊或疑似IFD的总体发生率为7.7%（1401例中的108例）；另有266例（19.0%）为可能的IFD。异基因或自体HSCT后，确诊/疑似IFD的发生率分别为8.9%（1053例中的94例）和4.0%（348例中的14例）。部分病例（108例中的14例）在移植前预处理期间发生。确诊/疑似IFD的累积发生率在移植后的第一个月急剧上升，6个月后，异基因移植受者的发生率显著高于自体移植受者（9.2%对3.5%；P = .001），且当干细胞来源于脐带血、骨髓和外周血时发生率更高（与其他来源相比，P = .02）。异基因HSCT中确诊/疑似IFD的独立危险因素为糖尿病、HLA匹配的无关供者、长期严重中性粒细胞减少（绝对中性粒细胞计数>500/mm³持续>14天）和免疫抑制剂（所有因素的比值比为2.0至3.4）。抗真菌预防具有独立的保护作用（P = .01）。既往IFD和长期严重中性粒细胞减少是自体移植患者中的重要独立危险因素（分别为P < .01，P = .04）。共有1175例（83.9%）患者接受了抗真菌预防（91.6%为三唑类），514例（36.7%）患者在医院接受了治疗性抗真菌药物治疗（89.1%为三唑类；中位治疗27天）。经验性、抢先性和靶向性抗真菌药物的使用分别占病例的82.3%、13.6%和4.1%。确诊（16例中的5例；31.3%）、疑似（92例中的20例；21.7%）或可能（266例中的61例；22.9%）IFD患者的总体死亡率（13.4%；188例死亡）显著更高；异基因（1053例中的171例；16.2%）而非自体（348例中的17例；4.9%）HSCT患者，且接受抢先性（18.6%）而非经验性（6.1%）或靶向性（9.5%）抗真菌治疗的患者死亡率显著更高（P = .002）。欢迎在预防性抗真菌药物的选择和时机方面有所改进。医疗服务提供者应持续警惕异基因HSCT受者中IFD风险增加及相关死亡率，以及即使出院后仍存在的IFD持续风险。
