Hemophagocytic lymphohistiocytosis

Section editor
	Ronald S. Go, MD Mayo Clinic Rochester, MN

4 regimens on this page 4 variants on this page

Untreated

HLH-94 regimen

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Regimen

Study	Evidence
Henter et al. 1997 (HLH-94)	Non-randomized

Immunosuppressive therapy, initial

• Dexamethasone (Decadron) in a tapering schedule as follows:
  • 10 mg/m2/day (single or split doses not specified) for weeks 1 & 2
  • 5 mg/m2/day (single or split doses not specified) for weeks 3 & 4
  • 2.5 mg/m2/day (single or split doses not specified) for weeks 5 & 6
  • 1.25 mg/m2/day (single or split doses not specified) for week 7
  • Taper off during week 8 (exact schedule not specified)
• Etoposide (Vepesid) 150 mg/m² IV as follows:
  • Twice per week for weeks 1 & 2
  • Once per week for weeks 3 to 8
• Methotrexate (MTX) (dose not specified) IT once per week for weeks 3 to 6 in patients with progressive neurological symptoms and/or persisting abnormal cerebrospinal fluid findings.

Supportive medications

• Prophylactic cotrimoxazole (5 mg/kg of trimethoprim equivalent), three times weekly
• An oral antimycotic during initial dexamethasone phase

8-week course; patients without familial or persistent disease then stopped. Patients with familial, persistent, or relapsed disease were treated with up to one year of continuation therapy, until an allogeneic HCT could be performed, as follows:

Immunosuppressive therapy, continuation

• Dexamethasone (Decadron) 10 mg/m²/day PO for three days, every two weeks (even weeks)
• Etoposide (Vepesid) 150 mg/m² IV once every two weeks (odd weeks)
• Cyclosporine A aiming for trough blood levels of 200 mcg/L (not clear from the paper whether this is modified or non-modified)

Continued for up to 52 weeks

References

1. HLH-94: Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH, Gadner H, Imashuku S, Janka-Schaub G, Komp D, Ladisch S, Webb D; HLH study Group of the Histiocyte Society. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. Med Pediatr Oncol. 1997 May;28(5):342-7. link to original article does not contain protocol PubMed
   1. Update: Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002 Oct 1;100(7):2367-73. link to original article contains verified protocol PubMed
   2. Update: Trottestam H, Horne A, Aricò M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI; Histiocyte Society. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood. 2011 Oct 27;118(17):4577-84. Epub 2011 Sep 6. link to original article contains verified protocol link to PMC article PubMed

Relapsed or refractory

DEP

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DEP: Doxil (Liposomal doxorubicin), Etoposide, MethylPrednisolone

Regimen

Study	Evidence	Efficacy
Wang et al. 2015a	Phase II	76%

Note: Liposomal doxorubicin could be repeated, although details are scant in the text. End of etoposide is also somewhat unclear.

Chemotherapy

• Pegylated liposomal doxorubicin (Doxil) 25 mg/m² IV once on day 1
• Etoposide (Vepesid) 100 mg/m² IV once per week
• Methylprednisolone (Solumedrol) as follows:
  • Days 1 to 3: 15 mg/kg/day
  • Days 4 to 6: 2 mg/kg/day
  • Days 7 to 10: 1 mg/kg/day
  • Days 11 to 14: 0.75 mg/kg/day
  • Days 15 to 21: 0.5 mg/kg/day
  • Days 22 to 28: 0.4 mg/kg/day
  • Days 29 to 35: 0.3 mg/kg/day
  • Days 36 to 42: 0.2 mg/kg/day
  • Days 43 to 49: 0.1 mg/kg/day

One course

References

1. Wang Y, Huang W, Hu L, Cen X, Li L, Wang J, Shen J, Wei N, Wang Z. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood. 2015 Nov 5;126(19):2186-92. Epub 2015 Aug 19. link to original article contains verified protocol link to PMC article PubMed