Outcomes in Invasive Pulmonary Aspergillosis Infections Complicated by Respiratory Viral Infections in Patients With Hematologic Malignancies: A Case-Control Study

Background. Data regarding invasive pulmonary aspergillosis (IPA) following respiratory viral infections (RVIs) in patients with leukemia and/or hematopoietic stem cell transplantation (LHSCT) are limited. Methods. We conducted a retrospective case-control study of post-RVI IPA (2006-2016). Cases were patients who underwent LHSCT and had RVI due to respiratory syncytial virus (RSV), influenza virus (INF), or parainfluenza virus (PIV) followed by culture-documented IPA within 6 weeks. Controls had IPA only. Results. We identified 54 cases and 142 controls. Among cases, 29 (54%) had PIV infection, 14 (26%) had INF infection, and 11 (20%) had RSV infection. The median time to IPA after RVI was 7 days. A greater percentage of cases (37 [69%]) than controls (52 [37%]) underwent allogeneic HSCT (P<.0001). Cases were more likely to be nonneutropenic (33 [61%] vs 56 [39%]; P=.009) and in hematologic remission (27 [50%] vs 39 [27%]; P=.003) before IPA. Cases were more likely to have monocytopenia (45 [83%] vs 99 [70%]; P=.05) and less likely to have severe neutropenia (21 [39%] vs 86 [61%]; P=.007) at IPA diagnosis. Prior use of an Aspergillus-active triazole was more common in cases (27 of 28 [96%] vs 50 of 74 [68%]; P=.0017). Median time to empirical antifungal therapy initiation was 2 days in both groups. Crude 42-day mortality rates did not differ between cases (22%) and controls (27%), but the 42-day mortality rate was higher among cases with IPA after RSV infection (45%) than among those with IPA following INF or PIV infection (13%; P=.05). Conclusions. IPA had comparable outcomes when it followed RVI in patients who underwent LHSCT, and post-RVI IPA occurred more frequently in patients with prior allogeneic HSCT and was associated with leukemia relapse and neutropenia.