Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step

Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal disorder of uncontrolled inflammation, usually affecting infants. Significant progress in the treatment of this disorder has been achieved during the last decade, and outcomes for larger series of patients have been reported in recent years. Although medical therapy has advanced, hematopoietic cell transplantation remains the only curative therapy for patients with the familial form of this disorder. Unfortunately, these patients have demonstrated relatively poor post-transplant outcomes for a nonmalignant disorder, with approximately 30% mortality in the first 100 days. Early deaths were attributable to infection, GVHD, and unusually high rates of primary nonengraftment, venoocclusive disease and pneumonitis. In addition, a significant number of deaths were due to HLH reactivation, a unique complication seen in this patient group. In contrast, late complications were relatively infrequent and essentially all patients with durable engraftment remained in remission indefinitely. In this review, we will discuss recent progress in the transplant management of patients with HLH and potential future strategies, including the use of reduced intensity conditioning regimens.