PURPOSE:
Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis and in 1983 the long-term survival was reported as 4%. Prompted by these poor results, in 1994 the Histiocyte Society developed a treatment strategy (HLH-94) which combined two previously reported regimens, chemotherapy and immunotherapy. HLH-94 is based on etoposide (VP-16), corticosteroids, cyclosporin A (CSA), and, in selected patients, IT MTX, prior to intended stem cell transplantation (SCT).

TIMELINE:
The Histiocyte Society launched the first international therapeutic study on HLH in 1994 (HLH-94). It started July 1, 1994, and closed for recruitment December 31, 2003.

OUTCOMES OF THE TRIAL:
Altogether 249 patients fulfilled inclusion criteria. At a median follow-up of 6.2 years, estimated 5-year probability-of-survival was 54±6%. Seventy-two patients (29%) died before SCT. In the 124 patients that underwent SCT, 5-year-survival was 66±9% with tendency to increased survival (p=0.064) in patients with non-active disease at SCT. Patients with familial disease had a 5-year-survival of 50%±13%. To conclude, HLH-94 chemo-immunotherapy considerably improved outcome in HLH.

PUBLICATIONS:

1. Henter JI, Arico M, Egeler M, Elinder G, Filipovich A, Favara B, Gadner H, Imashuku S, Janka G, Komp D, Ladisch S, Webb D. HLH-94: A treatment protocol for hemophagocytic lymphohistiocytosis. Med Pediatr Oncol 1997; 28: 342-47.

2. Henter JI, Samuelsson AC, Arico M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immuno-chemotherapy and bone marrow transplantation. Blood 2002; 100: 2367-2373.                           

3. Horne AC, Janka G, Egeler RM, Gadner H, Imashuku S, Ladisch S, Locatelli F, Montgomery SM, Webb D, Winiarski J, Filipovich AH, Henter JI.  Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis. Br J Haematol 2005; 129: 622-630.    

4. Horne AC, Trottestam H, Aricó M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI. Frequency and spectrum of CNS involvement in 193 children with hemophagocytic lymphohistiocytosis. Br J Haematol. 2008; 140: 327-35. 

5. Trottestam H, Horne AC, Arico M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI, Chemo immunotherapy for hemophagocytic lymphohistiocytosis: long term results of the HLH-94 treatment protocol. Blood 2011; 118: 4577-84.