Adolescents and Young Adults With Hemophagocytic Lymphohistiocytosis Who Undergo Allogeneic Hematopoietic Cell Transplantation Are At Increased Risk Of Mortality Compared To Younger Patients

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening disorder of immune deregulation characterized by overwhelming immune activation and inflammation. Primary HLH was once thought to affect predominantly infants and young children. However, with increasing awareness, HLH is being diagnosed in adolescents and young adults. Currently, allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy available for primary hemophagocytic lymphohistiocytosis (primary HLH). There is limited data on HCT outcome for adolescents and young adults with HLH. We reviewed the allogeneic HCT outcomes of 19 adolescents and young adults with HLH (12 males and 7 females) who underwent HCT from January 2000 to June 2013 at our center. The median age at transplantation was 18.2 years (range: 15.2 -27.2). The Majority (15/19) underwent reduced-intensity conditioning (RIC) regimen consisting of alemtuzumab, fludarabine, and melphalan. Thirteen patients received transplants from HLA- matched donors (10 MUD and 3 MSD). Bone marrow was the source of stem cells in 15 patients. The HCT outcome of this group was compared to outcome of children with HLH less than 15 years of age. Median follow up of adolescent and young adult patients following HCT is 280 days (range 9-1643 days). Mixed donor chimerism was noted in 20% (3/15) of patients who received RIC. Acute GVHD grade II-IV was noted in four patients. Overall survival for adolescent and young adult patients was 42.1% (8/19). In patients who received RIC, Kaplan Meier analysis revealed a long term estimated survival of 57%, compared to 75% for children less than 15 years of age (p=0.03). Cox proportional hazard modeling revealed a reduced risk of mortality in young patients undergoing RIC HCT compared to adolescent and young adult patients (HR 0.379 [0.154-0.933], p=0.035), controlling for donor match and source. Deaths in adolescent and young adult patients occurred from days +9 to +568 following HCT. The cause of death varied from fulminant bacterial sepsis (n=4), acute refractory GVHD (n=2), disseminated aspergillus and fungal sepsis (n=2), viral infection (n=2), and refractory chronic GVHD (n=1). In conclusion, adolescents and young adults with HLH who undergo allogeneic HCT are at increased risk of mortality compared to younger patients. Further studies are needed to identify risk factors and potential interventions to improve HCT outcome for adolescents and young adults with HLH.