View source for HLH-2004 for untreated hemophagocytic lymphohistiocytosis (HLH)

<includeonly>Source: [[HLH-2004 for untreated hemophagocytic lymphohistiocytosis (HLH)]] 
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==Regimen in use at== 
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[[Category:Chemotherapy regimens]]
[[Category:Hemophagocytic lymphohistiocytosis regimens]]
[[Category:Disease-specific regimens]]
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===Regimen===
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|'''Study'''
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
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|[https://www.researchgate.net/profile/Gritta_Janka2/publication/6851976_HLH-2004_Diagnostic_and_therapeutic_guidelines_for_hemophagocytic_lymphohistiocytosis/links/5421309f0cf203f155c61206/HLH-2004-Diagnostic-and-therapeutic-guidelines-for-hemophagocytic-lymphohistiocytosis.pdf Henter et al. 2007 (HLH-2004)]
|style="background-color:#EEEE00"|Non-randomized
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====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 modified (Neoral)|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 (Millipred)|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

Supportive medications:
*Prophylactic [[Trimethoprim/Sulfamethoxazole_(Bactrim_DS)|cotrimoxazole]] (5 mg/kg of trimethoprim equivalent), three times weekly, start on week 1 and treat onwards
*An oral [[:Category:Antifungals|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 modified (Neoral)|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

'''Used continuously, with allogeneic stem cell transplant done when possible'''

===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. [https://www.researchgate.net/profile/Gritta_Janka2/publication/6851976_HLH-2004_Diagnostic_and_therapeutic_guidelines_for_hemophagocytic_lymphohistiocytosis/links/5421309f0cf203f155c61206/HLH-2004-Diagnostic-and-therapeutic-guidelines-for-hemophagocytic-lymphohistiocytosis.pdf link to full article at ResearchGate] [http://onlinelibrary.wiley.com/doi/10.1002/pbc.21039/abstract;jsessionid=4E561DF344D9A0163C24F27F34D53ADF.f02t02 link to original article] '''contains verified protocol''' [https://www.researchgate.net/file.PostFileLoader.html?id=557ab7b36307d92f338b457a&assetKey=AS%3A273796236283904%401442289517969 link to study protocol] [https://www.ncbi.nlm.nih.gov/pubmed/16937360 PubMed]