Bonnet S, Duléry R, Regany K, Bouketouche M, Magro L, Coiteux V, Alfandari S, Berthon C, Quesnel B, Yakoub-Agha I
Department of Hematology, CHRU de Lille, 59037 Lille, France.
Department of Hematology, CHRU Saint-Antoine, AP-HP, 75012 Paris, France.
Curr Res Transl Med. 2017 Apr-Jun;65(2):77-81. doi: 10.1016/j.retram.2017.05.003. Epub 2017 Jul 5.
Antifungal prophylaxis (AP) has dramatically changed the epidemiology of invasive aspergillosis (IA). To better understand the differences in terms of clinical significance of IA between allogeneic stem cell transplantation (allo-SCT) recipients and patients treated for leukemia, we report a single-center study of 735 unselected consecutive patients treated between 2000 and 2004, before the era of systematic AP. Probable or confirmed IA were observed in 29 patients (2008 EORTC/MSG criteria), including 7/235 undergoing allo-SCT (5.2%), 19/380 treated for acute leukemia (5.0%), 1/116 for chronic lymphocytic leukemia (0.9%) and 2/104 for myelodysplastic syndrome (1.9%). In allo-SCT recipients, IA occurred later than in leukemia patients, after the neutropenic period. The median time between the last treatment and the diagnosis of IA was 231 days (range, 68-341) in allo-SCT recipients and 17 days (6-57) in leukemia patients (P<0.001). Importantly, the 7 cases of IA after allo- SCT occurred only in patients treated with corticosteroids for graft-versus-host disease (GVHD). Mortality directly related to IA was 24%. The 100-day, 2-year and 10-year overall survival were 42.9%, 0%, 0% in allo-SCT recipients compared to 68.1%, 18.2%, 13.6% in leukemia patients, respectively (P≥0.05). These poor outcomes were mainly attributable to non-relapse mortality (NRM). In conclusion, our data allows distinguishing 2 types of IA occurring at different time in the treatment course. In both cases, the NRM is very high and treatment remains challenging. Thus, systematic broad-spectrum AP against Aspergillus should be considered in acute leukemia patients during the neutropenic phase and in all patients undergoing allo-SCT who develop GVHD.
抗真菌预防（AP）显著改变了侵袭性曲霉病（IA）的流行病学。为了更好地理解异基因干细胞移植（allo-SCT）受者与白血病治疗患者在IA临床意义方面的差异，我们报告了一项单中心研究，该研究纳入了2000年至2004年期间在系统性AP时代之前连续治疗的735例未经筛选的患者。根据2008年欧洲癌症研究与治疗组织/侵袭性真菌感染协作组（EORTC/MSG）标准，在29例患者中观察到可能或确诊的IA，其中235例接受allo-SCT的患者中有7例（5.2%），380例急性白血病治疗患者中有19例（5.0%），116例慢性淋巴细胞白血病患者中有1例（0.9%），104例骨髓增生异常综合征患者中有2例（1.9%）。在allo-SCT受者中，IA发生时间晚于白血病患者，在中性粒细胞减少期之后。allo-SCT受者从最后一次治疗到IA诊断的中位时间为231天（范围68 - 341天），白血病患者为17天（6 - 57天）（P<0.001）。重要的是，allo-SCT后的7例IA仅发生在接受糖皮质激素治疗移植物抗宿主病（GVHD）的患者中。与IA直接相关的死亡率为24%。allo-SCT受者的100天、2年和10年总生存率分别为42.9%、0%、0%，而白血病患者分别为68.1%、18.2%、13.6%（P≥0.05）。这些不良结局主要归因于非复发死亡率（NRM）。总之，我们的数据显示在治疗过程中存在两种不同时间发生的IA类型。在这两种情况下，NRM都非常高，治疗仍然具有挑战性。因此，对于急性白血病患者在中性粒细胞减少期以及所有发生GVHD的allo-SCT患者，应考虑系统性应用针对曲霉菌的广谱AP。
