Early Use of Inhaled Ribavirin Can Improve Outcomes in High Risk Hematopoietic Stem Cell Transplant and Leukemia Patients with RSV Infection

Respiratory syncytial virus (RSV) in the immunocompromised adult can lead to significant morbidity and mortality. Most immunocompromised patients with RSV pneumonia present to a health care facility with an upper respiratory tract infection ∼1 week prior to the onset of pneumonia.  Overall, 40%–50% of RSV upper respiratory tract infections (URTI) in HCT recipients will progress to pneumonia. RSV pneumonia in HCT recipients is associated with fatality rates as high as 70–80%. Treatment of RSV pneumonia is primarily supportive.  The role of specific antiviral therapy remains uncertain.  We retrospectively reviewed RSV-infected patients with upper or lower respiratory tract infection (LRTI) diagnosed by antigen testing, polymerase chain reaction and/or culture from January 2007 through March 2013. In general, clinically stable URTI patients with an absolute lymphocyte count (ALC) > 300 received only supportive care. Patients presenting with URTI and lymphopenia (ALC ≤ 300) were preferentially treated with a course of inhaled ribavirin (IR) alone.  Those presenting with LRTI were preferentially treated with IR in combination with the RSV-specific humanized monoclonal antibody, Palivizumab.  We identified 60 consecutive patients who were diagnosed with RSV (median age 52 [21 - 72]) - 35 had URTI and 25 had LRTI.  Forty-one (71%) of the patients had received an allogeneic transplant, seven (12%) were post autologous transplant, while 10 (17%) were receiving treatment for acute leukemia.  Of the allogeneic transplant patients, 31 (51.6 %) were receiving immunosuppressants and 24 (40%) were being actively treated for graft-versus-host disease (GVHD).  The median (range) ANC and ALC at the time of RSV diagnosis was 1.6 (0 - 11) and 0.8 (0 - 7.3), respectively.  Among the 35 patients with URTI, 12 received IR while 23 did not.  None of the 12 patients treated with IR progressed to LRTI.  In contrast, 6 of the 23 untreated patients (24%) with URTI progressed to LRTI. Of the 31 patients with LRTI (25 initially diagnosed with LRTI and 6 patients who progressed from URTI to LRTI), there were four deaths occurring within 60 days of RSV diagnosis (two deaths directly from RSV, one from disease relapse, and one from GVHD).  In patients with LRTI (25 patients with LRTI at diagnosis plus 6 patients who progressed from URTI to LRTI), RSV-related mortality was (6.4%). On univariate analysis, only the presence of GVHD significantly predicted the development of LRTI in patients with URTI (P = .028); however, the use of inhaled ribavirin had a protective effect that was marginally significant (P= .074).  Early use of IR in high-risk transplant and leukemia patients can both reduce the progression from URTI to LRTI and improve the historically dismal outcomes of patients with RSV pneumonia.