Outcome Analysis of Invasive Aspergillosis in Hematologic Malignancy and Hematopoietic Stem Cell Transplant Patients: The Role of Novel Antimold Azoles

• Published in: The oncologist (Dayton, Ohio) Vol. 16; no. 7; pp. 1049 - 1060
• Main Authors: Ramos, Elizabeth R., Jiang, Ying, Hachem, Ray, Kassis, Christelle, Kontoyiannis, Dimitrios P., Raad, Issam
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01.07.2011
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents - therapeutic use; Aspergillosis - drug therapy; Aspergillosis - etiology; Aspergillosis - microbiology; Aspergillus; Azole; Azoles - therapeutic use; Child; Hematologic malignancy; Hematologic Neoplasms - microbiology; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Invasive aspergillosis; Male; Middle Aged; Outcome; Outcomes Research; Prognosis; Prognostic factor; Retrospective Studies; Salvage Therapy; Treatment Outcome; Young Adult
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2010-0290

Background. Invasive aspergillosis (IA) continues to be a leading cause of morbidity and mortality in hematologic malignancy (HM) patients. We evaluated the prognostic factors for IA in HM patients. Methods. In this retrospective study, we included all HM patients diagnosed with proven or probable IA between June 1993 and June 2008. Results. A total of 449 HM patients were analyzed, the majority of which (75%) had underlying leukemia. Multivariate logistic regression analysis showed that neutropenia for more than two weeks during IA, steroid use, and intensive care admission were independently associated with failure to respond to antifungal therapy, as well as increased IA‐attributable mortality (all p‐values < .01). Antifungal therapy with an antimold azole‐containing regimen (voriconazole or posaconazole) was also independently associated with improved response to treatment, as well as decreased IA‐attributable mortality (all p‐values < .0001). Survival analysis showed that primary or salvage therapy with a regimen that contained antimold azoles was significantly associated with improved survival (p < .001). Conclusions. In HM patients, persistent neutropenia and the need for intensive care are associated with failure to respond to antifungal therapy. Use of novel antimold azoles, either as primary or salvage therapy, improves the overall outcome and IA‐attributable death of HM patients with IA. 摘要 背景 侵袭性曲霉菌病（IA）一直是血液系统恶性肿瘤（HM）患者发病率和死亡的首要原因。本文旨在评估HM患者的IA预后因素。 方法. 本项回顾性研究纳入1993年6月 ~ 2008年6月确诊或临床诊断为IA的所有HM患者。 结果. 共449例HM患者参与分析，其中，多数（75%）为白血病患者。多元logistic回归分析显示，IA期间中性粒细胞缺乏症2周以上，使用类固醇激素和在重症监护室治疗是抗真菌治疗无效的独立因素，增加了IA患者的相关死亡率（所有P值均< 0.01）。采用含抗霉菌唑类药物（伏立康唑或泊沙康唑）方案抗真菌治疗可提高疗效，可降低IA相关死亡率（所有P值均< 0.0001）。生存分析显示，采用含抗霉菌唑类药物方案进行初始或挽救治疗均可改善生存（P < 0.001）。 结论. 对于HM患者，持续中性粒细胞缺乏症和需要重症监护等因素与抗真菌治疗无疗效相关。无论是初始还是挽救治疗，新型抗霉菌唑类药物的应用均可改善伴有IA的HM患者的预后和减少IA相关死亡。 Invasive aspergillosis (IA) continues to be a leading cause of morbidity and mortality in hematologic malignancy (HM) patients. In HM patients, persistent neutropenia and the need for intensive care are associated with failure to respond to antifungal therapy. Use of novel antimold azoles, either as primary or salvage therapy, improves the overall outcome and IA‐attributable death of HM patients with IA.