Gangneux Jean-Pierre, Padoin Christophe, Michallet Mauricette, Saillio Emeline, Kumichel Alexandra, Peffault de La Tour Régis, Ceballos Patrice, Gastinne Thomas, Pigneux Arnaud
Mycology Department, Centre Hospitalier Universitaire de Rennes, University Rennes, INSERM, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR S_1085, 35000 Rennes, France.
Pharmacy Department, CHU Martinique Site P. Zobda Quitman, 97261 Fort de France, Martinique, France.
J Fungi (Basel). 2020 Nov 12;6(4):281. doi: 10.3390/jof6040281.
Antifungal prophylaxis (AFP) is recommended by international guidelines for patients with acute myeloid leukaemia (AML) undergoing induction chemotherapy and allogeneic hematopoietic cell transplantation. Nonetheless, treatment of breakthrough fungal infections remains challenging. This observational, prospective, multicentre, non-comparative study of patients undergoing myelosuppressive and intensive chemotherapy for AML who are at high-risk of invasive fungal diseases (IFDs), describes AFP management and outcomes for 404 patients (65.6% newly diagnosed and 73.3% chemotherapy naïve). Ongoing chemotherapy started 1.0 ± 4.5 days before inclusion and represented induction therapy for 79% of participants. In 92.3% of patients, posaconazole was initially prescribed, and 8.2% of all patients underwent at least one treatment change after 17 ± 24 days, mainly due to medical conditions influencing AFP absorption (65%). The mean AFP period was 24 ± 32 days, 66.8% stopped their prophylaxis after the high-risk period and 31.2% switched to a non-prophylactic treatment (2/3 empirical, 1/3 pre-emptive/curative). Overall, 9/404 patients (2.2%) were diagnosed with probable or proven IFDs. During the follow-up, 94.3% showed no signs of infection. Altogether, 20 patients (5%) died, and three deaths (0.7%) were IFD-related. In conclusion, AFP was frequently prescribed and well tolerated by these AML patients, breakthrough infections incidence and IFD mortality were low and very few treatment changes were required.
国际指南建议，对于接受诱导化疗的急性髓系白血病（AML）患者以及接受异基因造血细胞移植的患者，应进行抗真菌预防（AFP）。尽管如此，突破性真菌感染的治疗仍然具有挑战性。这项针对接受骨髓抑制和强化化疗的AML患者（这些患者有侵袭性真菌病（IFD）的高风险）的观察性、前瞻性、多中心、非对照研究，描述了404例患者（65.6%为新诊断患者，73.3%为未接受过化疗的患者）的AFP管理及结果。纳入研究前1.0±4.5天开始进行正在进行的化疗，79%的参与者接受的是诱导治疗。92.3%的患者最初开具的是泊沙康唑，17±24天后，8.2%的所有患者至少进行了一次治疗调整，主要原因是影响AFP吸收的医疗状况（65%）。AFP的平均疗程为24±32天，66.8%的患者在高风险期后停止预防，31.2%的患者转为非预防性治疗（2/3为经验性治疗，1/3为抢先性/治愈性治疗）。总体而言，404例患者中有9例（2.2%）被诊断为可能或确诊的IFD。在随访期间，94.3%的患者未出现感染迹象。共有20例患者（5%）死亡，3例死亡（0.7%）与IFD相关。总之，这些AML患者经常接受AFP治疗且耐受性良好，突破性感染发生率和IFD死亡率较低，且几乎不需要进行治疗调整。
