Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

Study Overview
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Brief Summary
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Without therapy HLH is often fatal, and often rapidly fatal. The treatment protocol HLH-94 has improved survival markedly as compared to the survival earlier. We now aim to improve survival further.

Detailed Description
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The most dangerous period after HLH diagnosis is the first 2 months. In HLH-2004 we provide additional therapy during this period as compared to in HLH-94.

Official Title
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HLH-2004 Treatment Protocol

Conditions
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Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Etoposide
* Drug: Cyclosporin
* Procedure: Intrathecal therapy
* Procedure: Stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who fulfil the diagnostic criteria of HLH. Exclusion Criteria: Prior cytotoxic or cyclosporin treatment for HLH.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & Steroids<br>As compared to the HLH-94 treatment, the main changes are that Cyclosporin A is administered from day 1 and Intrathecal steroids are added to the intrathecal methotrexate. Drugs, dosage, frequency and duration are described in the paragraph Interventions below. | Drug: Dexamethasone<br>* 10 mg/m2 daily wk 1-2 5 mg/m2 daily wk 3-4 2.5 mg/m2 daily wk 5-6 1.25 mg/m2 daily wk 7 Steroids tapered wk 8 If continuation: Pulses every 2nd wk, 10 mg/m2 for 3 days<br>Drug: Etoposide<br>* 150 mg/m2 iv twice/wk (wk 1-2) 150 mg/m2 iv once/wk (wk 3-8) If continuation: 150 mg/m2 iv, every 2nd wk<br>Drug: Cyclosporin<br>* WK 1-8: - Aim at around 200 microgram/L (trough value). Start: 6 mg/kg daily (divided in 2 daily doses) wk 1, if kidney function is normal. If continuation: - Aim for around 200 microgram/L. Monitor GFR.<br>Procedure: Intrathecal therapy<br>* If at 2 wks there are progressive neurological symptoms or if an abnormal CSF (cell count and protein) has not improved, then give 4 wkly intrathecal inj. Be aware that some pat may have increased intracranial pressure. Methotrexate: <1 yr 6 mg, 1-2 yrs 8 mg, 2-3 yrs 10 mg, >3 yrs 12 mg. Prednisolone: <1 yr 4 mg, 1-2 yrs 6 mg, 2-3 yrs 8 mg, >3 yrs 10 mg.<br>Procedure: Stem cell transplant<br>* The SCT procedure is up to the treating physician. However, a suggested regimen is provided.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 1-year after diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late effects |  | 5-years after diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophagocytic lymphohistiocytosis