Outcome of respiratory syncytial virus lower respiratory tract disease in hematopoietic cell transplant recipients receiving aerosolized ribavirin: significance of stem cell source and oxygen requirement

Abstract

Respiratory syncytial virus (RSV) infection is an important complication after hematopoietic cell transplantation (HCT), and RSV lower respiratory tract disease (LRD) results in substantial early mortality and late airflow obstruction among survivors. Factors associated with poor outcome are unknown. We evaluated the effect of transplant and treatment factors on overall survival, mortality from respiratory failure, and pulmonary function among 82 HCT recipients who had RSV LRD between 1990 and 2011. All patients received aerosolized ribavirin. In multivariable analyses, only the use of marrow or cord blood as graft source (adjusted hazard ratio [aHR], 4.1; 95% confidence interval [CI], 1.8 to 9.0; P < .001) and oxygen requirement (aHR, 3.3; 95% CI, 1.5 to 6.7; P = .003) remained independently associated with overall mortality and death due to respiratory failure (aHR, 4.7; 95% CI, 1.8 to 13; P = .002 and aHR, 5.4; 95% CI, 1.8 to 16; P = .002, respectively). Antibody-based treatments, including intravenous immunoglobulin and palivizumab, were not independently associated with improved outcome and did not alter the associations of the graft source and oxygen requirements in statistical models. In conclusion, use of peripheral blood stem cells as graft source and lack of oxygen requirement at diagnosis appear to be important factors associated with improved survival of HCT recipients with RSV LRD. These results may explain differences in outcomes reported from RSV infection over time and may guide the design of future interventional trials.

Conflict of interest statement

Potential conflicts of interest. All other authors declare no competing financial interests.

Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

(A) Kaplan-Meier estimate of overall survival according to transplant year in HCT recipients after RSV LRD (p = 0.256, for three group comparison). (B) Cumulative incidence of death due to respiratory failure according to transplant year (p = 0.605). (C) Kaplan-Meier estimate of overall survival according to stem cell source in HCT recipients after RSV LRD (p < .001). (D) Cumulative incidence of death due to respiratory failure according to stem cell source (p = 0.006). (E) Kaplan-Meier estimate of overall survival according to the oxygen requirement at diagnosis in HCT recipients after RSV LRD (p = 0.001). (F) Cumulative incidence of death due to respiratory failure according to the oxygen requirement at diagnosis (p = 0.002).

Figure 2

(A) Kaplan-Meier estimate of overall survival according to stem cell source and the oxygen requirement at diagnosis (p = <.0001, for four group comparison). (B) Cumulative incidence of death due to respiratory failure according to stem cell source and the oxygen requirement at diagnosis (p = <.0001). (C) Kaplan-Meier estimate of overall survival according to stem cell source and mechanical ventilation requirement at diagnosis (p = <.0001). (D) Cumulative incidence of death due to respiratory failure according to stem cell source and mechanical ventilation requirement at diagnosis (p = <.0001).

Figure 3

Percentages of FEV1 (A), TLC (B), and DLCO (C) for predicted each value were shown at the time point of pre-LRD, day 60, and 1 year after RSV LRD. P-values for three parameters in %FEV1, %TLC, and %DLco were 0.249, 0.260, and 0.001, respectively. *, p < 0.05, by Wilcoxon rank sum test.