Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies

Abstract

Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo-HCT) recipients would be at higher risk for 60-day mortality.

Methods: We examined a retrospective cohort of adults with HM with or without HCT treated for RSV LRTI (n = 154) at our institution from 1996-2013. We defined possible RSV LRTI as RSV detected only in the upper respiratory tract with new radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable logistic regression analyses were performed to identify independent risk factors associated with 60-day all-cause mortality.

Results: Mortality was high in HM patients (25%), but there was no difference between those without HCT, autologous or allo-HCT recipients in logistic regression models. Separate multivariate models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8-24.2, P = 0.005) and lymphopenia (OR 3.7, 95% CI 1.7-8.2, P = 0.001) were associated with 60-day mortality. Proven LRTI was associated with higher 60-day mortality (neutropenia model: OR 4.7, 95%CI 1.7-13.5; lymphopenia model: OR 3.3, 95% CI 1.2-8.8), and higher ICU admission. In HCT recipients, high ISI and very severe immunodeficiency by SID criteria were associated with higher 60-day all-cause mortality.

Conclusions: Mortality is similarly high among HM patients without HCT and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60-day mortality.

Keywords: hematologic malignancy; hematopoietic cell transplantation; lower respiratory tract infection; mortality; respiratory syncytial virus.

Figure 1

Kaplan‐Meier survival cures for patients with HM but no HCT (solid line), allo‐HCT recipients (dashed line), and auto‐HCT recipients (alternating dots and dashes). There was no difference among survival rates between these groups (log‐rank test, P = 0.63)

Figure 2

Kaplan‐Meier survival curves for patients with possible (dashed line) and proven (solid line) RSV LRTI. Patients with proven RSV LRTI had significantly lower survival rates (log‐rank test, P < 0.001)

Figure 3

Kaplan‐Meier survival curves for patients who underwent bronchoscopy, stratified by microbiological results, and patients who did not undergo bronchoscopy (short dashed line). Patients who underwent bronchoscopy were further divided into BAL positive for RSV (solid black line), BAL positive for RSV and another respiratory pathogen (solid grey line), BAL positive for only a non‐RSV respiratory pathogen (long dashed line) and a BAL without growth (alternate short and long dashed lines). A log‐rank test showed significant differences in survival rates between groups (log‐rank test, P = 0.001)

Figure 4

Kaplan‐Meier survival curves for patients who started ribavirin therapy at the URTI stage of infection (solid line), ribavirin therapy at the LRTI stage of infection (long dashed line), or no ribavirin therapy (short dashed line). There was no significant difference in survival rates between these groups (log‐rank test, P = 0.16)

Figure 5

Kaplan‐Meier survival curves for HCT recipients with a) low, moderate, or high ISI and b) with MID, SID, or vSID. Both ISI and SID criteria predicted time to death (P < 0.001 for both scores)