High Readmission Costs in Patients with Respiratory Syncytial Virus Following Haematopoietic Stem Cell Transplantation
Authors: Gorcea Claudia M , Tholouli Eleni , Turner Andrew , Dignan Fiona L 
Published: October 2019

Abstract
Background
Respiratory syncytial virus (RSV) is a common cause of respiratory viral infections and is associated with increased morbidity and mortality in patients undergoing haematopoietic stem cell transplantation (HSCT). Little is known about the economic burden associated with RSV infection. We sought to analyse the readmission rates and costs associated with RSV infection in a single UK centre.
Patients and method
We undertook a retrospective case analysis of 48 consecutive patients diagnosed with RSV infection post HSCT between December 2010 and April 2014. The frequency of infection was 35/227 (17%) in allogeneic HSCT and 13/180 (7%) in autologous HSCT recipients.
Patient characteristics: male 28, median age 55 (range 23 to 71), diagnosis: acute leukaemia 15, multiple myeloma 16, myelodysplasia 6, aplastic anaemia 5, chronic leukaemia 3, other 3. In patients who had received an allogeneic transplant 22 had reduced intensity conditioning (RIC) regimen and 13 myeloablative conditioning. One patient received a cord blood transplant (CBT), 14 had a sibling allograft, whereas 20 had a volunteer unrelated donor (VUD) HSCT. In 20 patients, Alemtuzumab was part of the conditioning regimen. Twenty-seven patients were on immunosuppressive drugs (ciclosporin, mycophenolate mofetil, tacrolimus or corticosteroids) at time of diagnosis and 15 had active graft versus host disease (GVHD). At diagnosis, 37 patients were lymphopenic with lymphocytes below 1.5x10e9/L.
Diagnosis was established by polymerase chain reaction (PCR) assay for respiratory viruses and was performed as part of routine screening and in patients with respiratory symptoms. At diagnosis, 26 patients presented with lower respiratory tract infection (LRTI) as defined by new infiltrate on chest X-ray (CXR), signs on auscultation or hypoxia, whereas 22 experienced upper RTI. A CXR was performed in 39 patients and revealed infective or inflammatory changes in 12 patients, all with LRTI signs.
The primary indication for treatment was LRTI signs. Patients who were felt to be at high risk of progression to LRTI also received therapy. In total, 42 patients received Ribavirin: orally 16; aerosolised 17; aerosolised and orally combined 5; aerosolised and IV combined 4. Six patients received no treatment. The median duration of treatment was 7 days (range 5 to 47 days). Additional therapy was given: 13 patients received immunoglobulin replacement, 33 had concomitant antibiotic treatment and 11 also received antifungal treatment.
Results
Ribavirin was well tolerated with mild side effects associated with aerosolised administration: claustrophobia 2, headaches 1, nausea 1. Twenty patients were admitted for treatment of RSV infection, 6 of which required intensive care unit (ICU) admission including 4 who required invasive ventilation. Fifteen patients were treated as out-patients. Median length of ward stay was 10 days (range 4 to 55 days). ICU admission was associated with a median stay of 5 days (range 4 to 60 days). An additional 13 patients were diagnosed as in-patients and RSV was not felt to have extended their hospital stay. After a median follow-up period of 6.5 months (range 0-39): 33 patients are alive, 15 patients died. The causes of death were sepsis 3, relapsed disease 3, GVHD 2, gastrointestinal bleed 1, stroke 1. In 5 patients the cause of death was attributed to RSV infection, 4 having had previous ITU stay. No RSV-related deaths were recorded in the group treated with oral Ribavirin.
Admission costs were calculated based on the 2014 hospital tariff. Median cost was £3,700 for ward stay (range £1,480 to 20,350) and ICU admission with a median cost of £7,340 (range £5,872 to 88,080). The median cost of aerosolised ribavirin (6 g/day 2014 pharmacy prices) was £800 (range £570 to 1,596). The median cost of oral ribavirin (1000 mg/day based on 70kg) was £98 (range £28 to 658) and for the IV formulation median cost was £7,920 (range 3,394 to 12,445).
Conclusions
RSV in post HSCT patients remains a challenge due to the high frequency of infection and high rates and costs of readmission. Oral ribavirin may be an option for lower risk patients and strict isolation of patients in waiting areas to prevent transmission could be a cost effective measure. Prompt initiation of treatment in high risk patients is essential due to increased morbidity and mortality associated with RSV- associated LRTI.

Disclosures
No relevant conflicts of interest to declare.