Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

• Survival [ Time Frame: 1-year after diagnosis ] [ Designated as safety issue: No ]
  

• Late effects [ Time Frame: At last follow-up report ] [ Designated as safety issue: No ]
  

Drug: Dexamethasone
• Dexamethasone 10 mg/m2 daily, for the first 2 weeks (week 1-2).
• Dexamethasone 5 mg/m2 daily, for another 2 weeks (week 3-4).
• Dexamethasone 2.5 mg/m2 daily, for another 2 weeks (week 5-6)
• Dexamethasone 1.25 mg/m2 daily, for another week (week 7). Steroids are tapered and discontinued during week 8.

If continuation therapy is provided, then:

- Dexamethasone pulses every second week, 10 mg/m2 for 3 days.

Drug: Etoposide
• 150 mg/m2 iv twice weekly (week 1-2).
• 150 mg/m2 iv once weekly (week 3-8).

If continuation therapy is provided, then:

- 150 mg/m2 iv, every second week.

Drug: Cyclosporin

WEEK 1-8:

- The blood levels determine the dosages, aim at levels around 200 microgram/L (trough value) (monoclonal antibody assay of whole blood). Start with 6 mg/kg daily (divided in 2 daily doses) already week 1, if kidney function is normal.

If continuation therapy is provided, then:

- Aim for blood levels around 200 microgram/L, as above. Monitor GFR.

Procedure: Intrathecal therapy

The CSF is evaluated at diagnosis and after 2 weeks. If after 2 weeks there is clinical evidence of progressive neurological symptoms or if an abnormal CSF (cell count and protein) has not improved, additional CNS-therapy is initiated with 4 weekly intrathecal injections. Be aware that some patients 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

Suggested regimen:

Preparative Regimen

• Day -8,-7,-6,-5 Busulfan 2mg/kg po, or eq iv (as 1.6mg/kg), twice daily.
• Day -4 Etoposide 30 mg/kg iv (6 hr inf) (maximum 1800 mg)
• Day -3, -2 Cyclophosphamide 60 mg/kg iv (1 hr inf)
• Day 0 Marrow infusion (preferably ³3 x 108 nucleated cells/kg, non T-cell-depleted).

GVHD Prophylaxis:

1. CSA continuous infusion starting day -1 pre-transplant with 3 mg/kg until oral nutrition re-established, thereafter 12.5 mg/kg orally daily. Monitoring of CSA through concentration levels. The immunosuppression is discontinued after 6-12 months, if possible.

2. Short course methotrexate:

   • Day +1 15 mg/m2 iv
   • Day +3 10 mg/m2 iv
   • Day +6 10 mg/m2 iv Methotrexate may be substituted by mycophenolate mofetil (MMF).

Additional Treatment for URD

• ATG (12 hr inf iv) on days -3, -2 and -1 (according to manufacturers rec).
• Metronidazole 22 mg/kg daily (po or iv) from day -8 until discharge.

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.