A Study of Treatment of Inflammation Before Stem Cell Transplant in People With a Primary Immune Regulatory Disorder (PIRD) and/or an Autoinflammatory Condition

This clinical trial is studying whether treating inflammation before a stem cell transplant in patients with primary immune regulatory disorders (PIRDs) or autoinflammatory conditions improves transplant outcomes. PIRDs are genetic diseases where the immune system is dysregulated — attacking the body rather than protecting it — and allogeneic hematopoietic cell transplantation (HCT, or stem cell transplant) is often the only potential cure. However, active inflammation at the time of transplant significantly increases the risk of serious complications and death. Patients of any age who are receiving their first allogeneic stem cell transplant for a qualifying immune disorder, who have evidence of abnormal immune activation (measured by cytokine levels or inflammatory markers), and who have adequate organ function are eligible. Patients with uncontrolled infection, previous allogeneic transplant, HIV/HTLV infection, or who are pregnant are excluded. Participants will receive anti-inflammatory treatment (either emapalumab or fludarabine/dexamethasone, depending on the type of immune pathway involved) before their conditioning regimen and transplant. By bringing inflammation under control before transplant, researchers aim to create a safer biological environment that improves engraftment and reduces life-threatening transplant-related complications — giving patients with these devastating immune conditions the best possible chance of cure.