Department of Hematology, Spedali Civili Brescia, P.le Spedali Civili, Brescia, Italy.
Bone Marrow Transplant. 2011 Jan;46(1):132-6. doi: 10.1038/bmt.2010.76. Epub 2010 Apr 12.
Invasive fungal infections (IFIs) still pose major challenges in allogeneic hematopoietic SCT (HSCT), and effective antifungal prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the toxicity and the impact of aerosolized deoxycholate amphotericin B (aero-d-AmB) on respiratory tract IFIs (airways IFIs) in a homogeneous cohort of allogeneic HSCT patients, transplanted at one institution. Since 1999, 102 consecutive patients were transplanted from matched related (N = 71) or unrelated donor (MUD). Aero-d-AmB was administered for a median time of 16 days (range 2-45), in addition to systemic antifungal prophylaxis. Prolonged administration was neither associated with increased severe bacterial infections, nor with severe adverse events. In 16 patients in whom aero-d-AmB was delivered for less than 8 days, due to worsened clinical conditions or poor compliance, proven or probable airways IFIs were diagnosed in three cases (one mucormycosis and one fusariosis and one probable aspergillosis), whereas in 84 patients receiving aero-d-AmB for ≥ 8 days, one possible and one probable aspergillosis were diagnosed. A shortened administration (< 8 days) of aero-d-AmB was therefore associated with an increased risk of both total airways IFIs (P = 0.027) and proven/probable IFIs (P = 0.012). At multivariate analysis prolonged aero-d-AmB administration retained an independent protective effect on airways IFIs (P = 0.026) whereas a MUD transplant was associated with a borderline increase of IFIs risk (P=0.052). Overall, 95.1% of patients did not experience airways IFIs and no patient died due to IFIs. In this cohort of patients, prolonged aero-d-AmB seems to have a role in preventing respiratory tract IFIs, but a randomized controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.
侵袭性真菌病（IFI）仍然是异基因造血干细胞移植（HSCT）的主要挑战，有效的抗真菌预防仍然存在争议。本回顾性研究的目的是评估在同一机构接受异基因 HSCT 的同质患者人群中，使用雾化脱氧胆酸钠两性霉素 B（aero-d-AmB）的毒性和对呼吸道 IFI（气道 IFI）的影响。自 1999 年以来，共有 102 例患者接受了来自匹配的亲缘供体（N=71）或无关供体（MUD）的移植。除了全身抗真菌预防外，aero-d-AmB 的中位给药时间为 16 天（范围 2-45 天）。长时间给药既不会增加严重细菌感染，也不会导致严重不良事件。在 16 例因临床状况恶化或依从性差而在 8 天内停止使用 aero-d-AmB 的患者中，有 3 例（1 例毛霉菌病、1 例镰刀菌病和 1 例可能的曲霉菌病）诊断为确诊或拟诊气道 IFI，而在 84 例接受 aero-d-AmB 治疗≥8 天的患者中，诊断为 1 例可能和 1 例拟诊曲霉菌病。因此，aero-d-AmB 给药时间缩短（<8 天）与总气道 IFI（P=0.027）和确诊/拟诊 IFI（P=0.012）的风险增加相关。多变量分析表明，延长 aero-d-AmB 的给药时间与气道 IFI 具有独立的保护作用（P=0.026），而 MUD 移植与 IFI 风险的边界增加相关（P=0.052）。总体而言，95.1%的患者未发生气道 IFI，也没有患者因 IFI 而死亡。在本队列患者中，延长 aero-d-AmB 似乎可预防呼吸道 IFI，但推荐进行随机对照试验以验证该预防措施在异基因 HSCT 中的作用。
