Birgitta Versluijs

146 Discussion The high rates of failure to therapy and overall mortality are comparable to those re- ported by other groups. 5-7,16 For the treatment of IPS in children only a few studies were done. In the only multicenter trial, etanercept, a TNF receptor inhibitor, was added to systemic corticosteroids. 6 Complete response rate of 71%, with 1-year survival in 63 % of patients, compares superior to other reports. 17-19 Most literature on the treatment of BOS after HCT in children is on corticosteroid therapy, with reported response rates of 33-80%. 16,20-22 In some studies azithromycin and/or pravachol were added to cortico- steroids. 20,21 The response rate in our cohort is comparable with others, but pulmonary outcome in survivors seems much better. In most studies stabilization of PFT occurs, in our cohort the majority of survivors had normalization of PFT within 1-2 years. Extended systemic steroid courses are associated with high mortality from infectious complications. Ongoing clinical trials on effective and less toxic treatment of cGVHD and Allo-LS include studies on Fluticasone-Azithromycin-Montelukast (FAM), Ciclos- porin inhalation, Pirfenidone, neutrophil elastase inhibitors, Bortezomib, Everolimus, Extra Corporal Photopheresis, anti-TNF and JAK1/2 inhibitors (clinicaltrials.gov). Given the suggestion that —after initial normalization— PFT decreases over time, fol- low up of this cohort of survivors is important, as we know that pulmonary late effects of chemotherapy and HCT continue to occur over time, and most studies only start chec- king PFT 5 years after treatment. 23 In conclusion, Allo-LS is a severe complication of HCT associated with poor survival, especially for patients who develop Allo-LS after a period of GvHD requiring systemic treatment, those who need mechanical ventilation at diagnosis of Allo-LS, and BOS pa- tients with inadequate increase of FEV1% after the first MP-pulse. Early recognition of therapy failure is crucial and novel treatment strategies are warranted in these high risk patients to improve survival. 8