Chemo-immunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol

Helena Trottestam, AnnaCarin Horne, Maurizio Aricò, R Maarten Egeler, Alexandra H Filipovich, Helmut Gadner, Shinsaku Imashuku, Stephan Ladisch, David Webb, Gritta Janka and Jan-Inge Henter


Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether 249 patients fulfilled inclusion criteria and started HLH-94 therapy July 1994-December 2003; 227 (91%) with follow-up ≥5-years. At a median follow-up of 6.2 years, estimated 5-year probability-of-survival was 54±6%. Seventy-two patients (29%) died before HSCT; sixty-four within the first year, 97% of which had active disease. In 124 patients that underwent HSCT, 5-year-survival was 66±9% with tendency to increased survival (p=0.064) in patients with non-active disease at HSCT. Patients with familial disease had a 5-year-survival of 50%±13%; none survived without HSCT. Patients deceased during the first two months more often had jaundice, edema and elevated creatinine. Forty-nine non-transplanted patients (20%) were alive without signs of HLH activity and off-therapy >1-year; they presented at older age (p<0.001), were more often female (p=0.011) and less often had CNS-disease (p<0.001) or hepatomegaly (p=0.007). To conclude, HLH-94 chemo-immunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurological late-effects.

  • Submitted June 2, 2011.
  • Accepted August 19, 2011.