Role of Hematopoietic Cell Transplantation in Pediatric and Adult Hemophagocytic Lymphohistiocytosis—Remaining Unknowns and Challenges

The main indication for allogeneic HSCT in children is primary/familial HLH but indications in adults are diverse, including malignancy-associated HLH. Matched related donors have historically been the preferred stem cell source (if not sharing predisposing genetics) followed closely by unrelated donors, but haploidentical transplants are proving feasible. Choice of conditioning regimen between myeloablative and reduced-intensity (RIC) involves trade-offs between early toxicity, particularly veno-occlusive disease, and additional cellular infusions to address graft failure or poor chimerism. Allogeneic HSCT for HLH is most successful when primary disease is under control, so coordination between initial/salvage therapy and transplant initiation is key.