Birgitta Versluijs

158 Predictors for allo-LS The primary aim of this thesis was to investigate predictors, diagnostic tools and deter- minants for outcome in Allo-immune mediated Lung Syndromes (Allo-LS) after pedia- tric Hematopoietic Cell Transplantation (HCT). In this Chapter the main findings are discussed in the context of current literature, with their implications for patient care and future research. What are predictors for allo-LS? Studies evaluating predictors for Allo-LS in adults are scarce, and they present con- flicting results. For IPS aGVHD, TBI conditioning, busulfan conditioning, age, malig- nant disease and unrelated donor are all identified as risk factors. 1,2 For BOS cGVHD, aGVHD grade II-IV, PBSC grafts, HLA disparity, high donor age, male gender, cigarette smoking history, hypogammaglobinemia, pre-existing lung disease and Respiratory Vi- rus (RV) infections are thought to be predictors. 3,4 A systematic search of the literature on predictors for non-infectious pulmonary compli- cations after allogeneic HCT in children revealed 17 studies, including our own studies as described in Chapter 3 and Chapter 7 . 5,6 All studies with more than 5 children were selected. All studies analyze the role of general patient characteristics, HCT characteris- tics, aGVHD and cGVHD on pulmonary endpoints. Some studies have special focus on biomarkers, innate immunity, drug reactions and the presence of Respiratory Viruses pre-HCT. Table 1 shows an overview of the data. Limitations of the studies are their retrospective nature and small numbers of patients. When comparing the results of the studies one also has to consider the varying end- points (decline in Pulmonary Function Tests or clinical diagnosis like IPS and BOS) and the different statistical methods used for analyses. The most consistent overall result is the strong association of aGVHD and cGVHD with Allo-LS, 7-13 although some groups did not find this relation. 14,15 Our group was the first to specifically study RV early during HCT 5,6 and we found a strong association with the occurrence of Allo-LS (HR 8.37, 95% CI 1.78-39.43, p=0.007). In most other studies, RV was an exclusion criterion for Allo-LS, so nothing is noted on incidence or impact of viral infections. Although Duncan et al. 13 do mention a high incidence of early viral infections in patients developing BOS, it was no significant pre- dictor however. This point will be further elucidated in the next section on Respiratory Viruses (“Why study Respiratory Viruses after lung transplantation and HCT?” and “RV and Allo-LS”). 9