Birgitta Versluijs

163 Discussion RSV and influenza virus are thought to be more virulent than other RV like rhinovirus. 26 Recent reports however, also show an important role for rhinovirus in lung disease after HCT. 28 In a large prospective study, including adults and children undergoing allogeneic HCT, clinical outcomes associated with RV detected prior to HCT were analyzed. 29 Multiplex PCR-testing for RV was done on nasal washes or nasopharyngeal swabs. In 25 % of pa- tients they found a RV, 22% of them being asymptomatic. RV positive patients were sig- nificantly younger and had higher risk underlying disease with lower lymphocyte count. Overall mortality at day 100 was significantly higher in RV-patients than in non-RV pa- tients, patients with rhinovirus performing worse compared to the other RV (like RSV, influenza). In 28% of the deceased patients the cause of death was directly related to the pre-HCT RV. This study largely supports our findings (as described in Chapter 3 and 7), with high prevalence of RV in patients prior to HCT, also in asymptomatic patients, especially in children, when using modern high sensitive virus detection methods. They also showed persistence of the RV after HCT in 40%, and direct progression to LRTI only in 4% of patients. Rhinovirus was at least as pathologic as the other RV. Comments could be made about the stated relation between RV and death. It is impor- tant to realize that it is hard to distinguish death from RV pneumonia from Allo-LS. Given the time of death (median day + 32), and the description of clinical symptoms oc- curring weeks after first detection of RV with hypoxia, alveolar damage and pulmonary infiltrates, this might well all be allo-immune mediated lung disease. It would also be very interesting to see the data on follow up after day + 100, with regard to the develop- ment of BOS. In Chapter 6 we discuss the risks of Respiratory Syncytial Virus (RSV) during HCT. In ge- neral the literature estimates the risk of progression from RSV-URTI to -LRTI at around 50%, with RSV-related mortality rates varying between 10-55%. 25,27,30 These figures are found in the context of RSV treatment with antivirals. In adults, effect of treatment with ribavirin on progression to LRTI and RSV-related mortality is suggested, but in children this is unclear. In our small case series of untreated RSV-positive HCT recipients, we saw progression to mild LRTI in 38% and no RSV related deaths. Symptoms of LRTI occur- red rather late after the detection of RSV, coinciding with neutrophil engraftment and early T-cell reconstitution. Our observation suggests a role for immunity in the sympto- matology of RSV disease after HCT. This is consistent with an ongoing discussion in the field of RSV bronchiolitis. What drives disease? Is it high viral load, is it an excessive immune response, or both? 31 In our cohort of patients there were no RSV related deaths. We do not think that the risk of 9