Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies

Abstract

Respiratory viruses (RVs) are known to be major causes of morbidity and mortality in recipients of hematopoietic stem cell transplants (HSCTs), but prospective long-term studies are lacking. We prospectively screened all adult HSCT recipients (172 allogeneic [alloHSCT] and 240 autologous [autoHSCT]) who underwent transplantation during a 4-year period (1999 to 2003) for the development of a first episode of symptomatic upper respiratory tract infections and/or lower respiratory tract infections (LRTI) by an RV. RVs studied were influenza A and B viruses (n=39), human respiratory syncytial virus (n=19), human adenoviruses (n=11), human parainfluenza viruses 1 to 3 (n=8), human enteroviruses (n=5), human rhinoviruses (n=3), and the recently discovered human metapneumoviruses (n=19). During the study, 51 and 32 cases of RV symptomatic infections were identified of alloHSCT and autoHSCT recipients (2-year incidence, 29% and 14%, respectively). Risk factors for progression of upper respiratory tract infection to LRTI included severe (<0.2x10(9)/L) and moderate (<0.2x10(9)/L) lymphocytopenia in alloHSCT (P=.02) and autoHSCT (P=.03). Death from LRTI was attributed to an RV in 8 alloHSCT recipients. Symptomatic RV had no effect on 2-year outcomes, with the possible exception of influenza A and B virus infections in autoHSCT: these were associated with nonrelapse mortality (P=.02). In conclusion, this prospective trial allows an estimation of the minimum incidence of a first RV infection in adult HSCT recipients and identifies risk factors for acquisition of an RV infection and progression to LRTI; this should aid in the design of future studies. In addition, human metapneumovirus should be added to the potentially serious causes of RV infections in HSCT.

Figure 1

Cumulative incidence of development of a first documented episode of respiratory virus infection in allogeneic transplant recipients. A, Incidence in 86 patients who developed cGVHD according to whether they had (heavy line) or did not have (light line) close household contact with children (<12 years): this incidence was 45% and 19%, respectively, on day +720. B, Incidence in 57 evaluable patients who did not develop cGVHD according to whether they had (heavy line) or did not have (light line) close household contact with children (< 12 years): this incidence was 29% and 11%, respectively, on day +720.

Figure 2

Cumulative incidence of development of a first documented episode of respiratory virus infection in autoHSCT recipients. A, Incidence in 92 patients with advanced underlying disease status at transplantation according to whether they had (heavy line) or did not have (light line) close household contact with children (<12 years): this incidence was 18% and 9%, respectively, on day +720. B, Incidence in 148 patients with early underlying disease status at transplantation according to whether they had (heavy line) or did not have (light line) close household contact with children (<12 years): this incidence was 10% and 4%, respectively, on day +720.