Birgitta Versluijs

173 Discussion What is the long term pulmonary outcome of children after Allo-LS? Owing to an increased number of patients undergoing HCT and better survival rates, the population of HCT-recipients surviving into adulthood is growing. More and more is learnt about long term side effects of childhood cancer treatment, including HCT. Direct pulmonary toxicity of chemotherapy and radiation, combined with low grade infections and GVHD have impact on lung function years after treatment. Other treatment related morbidity (like cardiovascular side effects, impaired growth of thorax) and exogenous factors (smoking) also play a role. In Chapter 2 these themes are reviewed. International collaboration is needed to establish a common vision and integrated stra- tegy on guidelines for surveillance of pulmonary dysfunctions in childhood cancer survi- vors to optimize quality of care and improve quality of life in survivors (The International Late Effects of Childhood Cancer Guideline Harmonization Group, IGHG, www.ighg. org). Follow-up of HCT survivors in our center, consists of regular visits to a specialized late effect outpatient clinic, standardized history taking and physical examination, and PFT 5 and 10 years after HCT in all who received TBI or busulfan. From our study in Allo-LS patients, as described in Chapter 8 , we have learnt that in survivors of Allo-LS PFT restores to lower levels of normal within 1-2 years. With longer follow up PFT seems to decline again, but solid data are lacking. Therefore we recom- mend closer monitoring with more frequent PFT screening in patients after Allo-LS. It is conceivable that lungs that have been target for Allo-LS, are prone for further damage and fibrotic processes on top of prior injury. Early detection of decrease in pulmonary function will enable timely intervention with immunosuppression, bronchodilators, vac- cination, antibiotic prophylaxis or physiotherapy. What are future perspectives for research? To further elucidate the pathophysiologic processes underlying IPS and BOS, research is needed. There should be focus on the role of tissue damage and the immunological pathways involved. This will be done in bronchial epithelial cultures or in human airway organoids made from stem cells derived from BAL material. In these models the effect of Respiratory Virus or other “damaging” triggers can be studied by measuring cytokines, antigen expression, gene profiling etcetera. This will be done in the presence or absence of neutrophils and T cells. This can be done while blocking certain pathways. We could study allogeneic and autologous settings. And ideally both luminal and basolateral ef- fects could be observed. From there we could study preventive strategies to decrease tis- sue damage and test new drugs to control immune response and minimize the fibrotic process in the lungs. 9