Life-threatening hemophagocytic syndromes: current outcomes with hematopoietic stem cell transplantation.

Life-threatening hemophagocytic syndromes represent a subset of genetic disorders of inflammation. Many are rapidly lethal and can only be definitively treated at the present time with allogeneic hematopoietic stem cell transplantation (HSCT). In this report, current results with allogeneic transplantation for Hemophagocytic Lymphohistiocytosis (HLH) are described. HLH typically presents symptomatically during infancy and early childhood and can be identified by a constellation of numerous physical findings and laboratory tests indicative of overwhelming inflammation. The majority of patients with familial HLH lack natural killer (NK) cell function; in approximately 50% of cases the specific underlying genetic cause can now be discerned. Effective treatment consists of initial combination therapy with proapoptotic chemotherapy (typically etoposide) and anti-inflammatory therapies (principally steroids) in addition to aggressive supportive care, followed by allogeneic HSCT from the best available donor. Over the past 25 yr, through collaborative worldwide efforts, survival of children with HLH and related disorders has improved from 5% at 1 yr after diagnosis to greater than 50% 3-5 yr after diagnosis.