Respiratory Infections and Activity of Anti-Flu Vaccine in Patients with Lymphoma and Multiple Myeloma
Authors: Lavi Noa , Hardak Emilia , Oren Ilana , Avivi Irit 
Published: October 2019

Abstract
Introduction: The significance of viral respiratory infections (VRI) and efficacy of anti-flu vaccine in patients (pts) with lymphoproliferative malignancies (LPM) have not been fully elucidated. The current large comprehensive study was designed to evaluate the incidence of respiratory infections in LPM pts, define clinical significance of VRI and assess the impact of anti-flu vaccine on RI prevention in this population.
Methods: All consecutive pts, diagnosed either with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), followed at the Rambam Hematology Outpatient Unit between 01/2011 and 03/2012 (during or after anti-cancer therapy or untreated) were evaluated. Data regarding anti-lymphoma/MM therapy used, respiratory infections occurring during the study period, tests performed to assess these infections (focusing on viral ones), administration of anti-flu vaccine and infection-related outcome were recorded. Samples of nasopharyngeal aspirate (NPA) or bronchoalveolar lavage (BAL) were evaluated for VRI pathogens using both immunofluorescence and polymerase chain reaction (PCR) methods.
Results: Five hundred and sixty two respiratory infection episodes were reported in 369 pts. In 224 (40%) episodes, VRI investigation was performed using either NPA (n=180) or BAL (n=44) samples. The decision regarding the sample source was taken based on the respiratory infection severity.
The cohort screened for VRI included a larger proportion of pts receiving anti-cancer therapy during the study period than the non-screened cohort (70% vs 30%, respectively, p<0.01). The number of respiratory episodes requiring hospitalization for their respiratory infection was higher in the former cohort (54% vs 18%). One hundred fifty two screened episodes were community-acquired (50 required hospitalization) and 72 were hospital-acquired.
Fever was the most common clinical symptom in screened episodes (n=111, 50%), followed by cough (n=91, 41%), dyspnea (n= 87, 39%), runny nose (n=47, 21%), respiratory distress (n=45, 20%): with decreased O2 saturation (n=35, 16%) and mechanical ventilation (n=10, 4%). In 12% and 23% of episodes, respectively, neutropenia and significant hypogammaglobinemia (IgG <500 mg/dl) were revealed.
VRI were identified in 66/224 episodes (29%), 59 episodes were viral infections and 7 - co-infections (viral with another pathogen). Sixty viral episodes were diagnosed in pts with upper respiratory tract infections and 6 in pts with pneumonia.
Cough, abnormal lung physical findings and hypogammaglobinemia were statistically more frequent in pts with viral infections vs those with other respiratory infections. Viral infections were treated according to pathogens recognized. Tamiflu was prescribed for influenza infections and ribavirin was given for part of the respiratory syncytial virus (RSV) infections. Supportive treatment only was given for parainfluensa and metapneumovirus infections.
Twelve episodes of VRI, developed outside of hospital, required hospitalization (5%) and 2 of these episodes resulted in death. The most frequent viral infection was Influenza A (22 cases), followed by RSV (14 cases), parainfluenza and metapneumovirus (11 cases each). Less frequent viral pathogens were Influenza B (6 cases), and adenovirus (2 cases). Seven cases (10%) were accompanied with a secondary bacterial or fungal infection. Notably, 3 of the 10 pts diagnosed with RSV infection had a concurrent Aspergillus infection.
Data regarding anti-flu vaccination were available in 701 pts; 431 pts (61%) were vaccinated. In a univariate analysis, anti-flu vaccination was found to have no impact on the respiratory infection frequency (51% vs 48.9%, p=0.752).
Among pts with VRI, 49% did and 45% did not previously receive anti-flu vaccination (p=0.95). This vaccination had no effect on the VRI incidence in the investigated episodes.
Conclusions: VRI, although frequent, are usually associated with a good outcome in LPM pts. Presence of cough and abnormal pulmonary examination were found to predict a positive screen for a viral pathogen. Influenza and RSV, both potentially treatable with Tamiflu and ribavirin, respectively, were responsible for 55% of VRI episodes, justifying a wider use of viral screening in LPM pts. Anti-flu vaccination has not proved its efficacy either in preventing viral infections or in reducing the entire incidence of respiratory infections in these pts.

Disclosures
No relevant conflicts of interest to declare.