Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

Overview

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.

Full Title of Study: “HLH-2004 Treatment Protocol”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2011

Detailed Description

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.

Interventions

  • Drug: Dexamethasone
    • 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
  • Drug: Etoposide
    • 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
  • Drug: Cyclosporin
    • 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.
  • Procedure: Intrathecal therapy
    • 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.
  • Procedure: Stem cell transplant
    • The SCT procedure is up to the treating physician. However, a suggested regimen is provided.

Arms, Groups and Cohorts

  • Experimental: Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & Steroids
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Survival
    • Time Frame: 1-year after diagnosis

Secondary Measures

  • Late effects
    • Time Frame: 5-years after diagnosis

Participating in This Clinical Trial

Inclusion Criteria

  • Patients who fulfil the diagnostic criteria of HLH. Exclusion Criteria:

  • Prior cytotoxic or cyclosporin treatment for HLH.

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Karolinska University Hospital
  • Collaborator
    • Azienda Ospedaliero, Universitaria Meyer
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jan-Inge Henter, Professor – Karolinska University Hospital
  • Overall Official(s)
    • Jan-Inge Henter, MD, PhD, Principal Investigator, Karolinska Institutet

References

Henter JI, Horne A, Arico 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. doi: 10.1002/pbc.21039.

Citations Reporting on Results

Bergsten E, Horne A, Arico M, Astigarraga I, Egeler RM, Filipovich AH, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Montgomery S, Nanduri V, Rosso D, Henter JI. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017 Dec 21;130(25):2728-2738. doi: 10.1182/blood-2017-06-788349. Epub 2017 Sep 21.

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