HLH-2004 for untreated hemophagocytic lymphohistiocytosis (HLH)
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Regimen in use at
Regimen
Study | Evidence |
Henter et al. 2007 (HLH-2004) | Non-randomized |
Initial therapy
- Start allogeneic stem cell transplant (SCT) donor search
- Dexamethasone (Decadron) in a tapering schedule as follows:
- Weeks 1 & 2: dexamethasone 10 mg/m2 (route not specified) once per day
- Weeks 3 & 4: dexamethasone 5 mg/m2 (route not specified) once per day
- Weeks 5 & 6: dexamethasone 2.5 mg/m2 (route not specified) once per day
- Week 7: dexamethasone 1.25 mg/m2 (route not specified) once per day
- Week 8: "taper then discontinue"
- Etoposide (Vepesid) as follows:
- Weeks 1 & 2: etoposide 150 mg/m2 IV twice per week
- Weeks 3 to 8: etoposide 150 mg/m2 IV once per week
- Cyclosporine A 3 mg/kg/dose by mouth twice per day (total dose per day is 6 mg/kg), if normal kidney function. Then, titrate doses with goal of levels around 200 mcg/L (monoclonal, trough level). It was not clear from the paper whether this is modified or non-modified cyclosporine.
- Intrathecal therapy to "start only if progressive neurological symptoms or if an abnormal CSF has not improved," maximum of 4 doses, as follows:
- Weeks 3 to 6: Methotrexate (MTX) (dosed by age as listed below) IT once per week. Methotrexate doses by age:
- less than 1 year old: 6 mg each dose
- 1 to 2 years old: 8 mg each dose
- 2 to 3 years old: 10 mg each dose
- greater than 3 years old: 12 mg each dose
- Weeks 3 to 6: Prednisolone IT once per week. Prednisolone doses by age:
- less than 1 year old: 4 mg each dose
- 1 to 2 years old: 6 mg each dose
- 2 to 3 years old: 8 mg each dose
- greater than 3 years old: 10 mg each dose
- Weeks 3 to 6: Methotrexate (MTX) (dosed by age as listed below) IT once per week. Methotrexate doses by age:
Supportive medications:
- Prophylactic cotrimoxazole (5 mg/kg of trimethoprim equivalent), three times weekly, start on week 1 and treat onwards
- An oral antimycotic from weeks 1 to 9
- IvIG 0.5 g/kg IV once every 4 weeks
- "Gastroprotection suggested" for weeks 1 to 9
8-week course; patients with resolved, non-familial, non-genetically verified disease stopped therapy. Patients with familial, genetically verified, persistent, or reactivation/relapsed disease continued to continuation therapy, until an allogeneic HCT could be performed, as follows:
Continuation therapy
Starts during week 9.
- Dexamethasone (Decadron) 10 mg/m2 (route not specified) once per day for three days, every two weeks (on even weeks)
- Etoposide (Vepesid) 150 mg/m2 IV once every two weeks (on odd weeks)
- Cyclosporine A by mouth twice per day, aiming for trough blood levels of 200 mcg/L (not clear from the paper whether this is modified or non-modified)
- Proceed with allogeneic stem cell transplant (SCT) as soon as an acceptable donor is found, such as:
- HLA-idential record donor
- Matched unrelated donor
- Mismatched unrelated donor
- Family haploidentical donor
Continuous
References
- Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. link to full article at ResearchGate link to original article contains verified protocol link to study protocol PubMed