Introduction Survival is dismal for the 40-60% of children with MDS who relapse post allogeneic HCT1,2,3. Strategies to decrease relapse risk include use of cytoreduction prior to HCT or maintenance treatment after HCT, data on the utility of these approaches remains limited4-12. Rapid withdrawal of immune suppression or use of donor lymphocyte infusion (DLI) can enhance the graft versus leukemia effect and achieve disease control in some cases13,14. Addition of hypomethylating agents to DLI may provide additional benefit15 and second HCT should be considered16-21. While several novel therapies may alter the future landscape of MDS therapy22-28 (Table 1), the optimal approach to relapsed pediatric MDS remains unclear. We report the management of a child who relapsed less than 70 days after initial HCT. Our approach demonstrates that multimodal therapy may permit prolonged survival with excellent quality of life (QOL) despite lack of long-term cure.

In recent years, a number of monogenic disorders have been described that are characterized by immune dysregulation. A subset of these ‘primary immune regulatory disorders’ can cause severe interstitial lung disease, often recognized in late childhood or adolescence. Patients presenting to pulmonary clinic may have long and complex medical histories but lack a unifying genetic diagnosis. It is crucial for pulmonologists to recognize features suggestive of multisystem immune dysregulation and to initiate genetic workup, since targeted therapies based on underlying genetics may halt or even reverese pulmonary disease progression. Through such an approach, our center has been able to diagnose and treat a cohort of patients with interstitial lung disease from gene defects that affect immune regulation. Here we present representative cases related to pathogenic mutations in three distinct pathways and summarize disease manifestations and treatment approaches. We conclude with a discussion of our perspective on the outstanding challenges for diagnosing and managing these complex life-threatening and chronic disorders.