Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (R-HLH)

The purpose of this project is to study the survival of patients until Haematopoietic Stem Cell Transplantation following the use of Ruxolitinib as first-line treatment associated to corticosteroids in primary HLH.

Inclusion CriteriaPatient aged 0 to 22 yearsPatient with HLH syndrome confirmed by at least one of the two criteria:Confirmed genetic diagnosis of a condition predisposing to primary HLH (see table 1 and table 2) or abnormal expression of perforin, MUNC13-4, SAP or XIAP in FACS and/or positive family history ORPresence of at least 5 of the 8 following HLH diagnostic criteria:FeverSplenomegalyCytopenia (affecting at least two cell lineages)Haemoglobin < 9 g/dl (<10 g/dL in neonates)Platelets < 100,000/µLAbsolute neutrophil count (ANC) < 1,000/µLHypertriglyceridemia and/or hypofibrinogenemiaFasting triglycerides ≥ 3 mmol/lFibrinogen <1.5 g/LHaemophagocytosis found in a histological sample (without evidence of a malignant process or an underlying rheumatic disorder)Decreased or absent NK functionFerritin ≥ 500 µg/lPresence of activated T cells in the immune phenotyping as evidenced by expression of the activation marker DR (superior to the normal value of the laboratory) OR CD25 soluble (sIL-2 receptor) ≥ 2,400 U/mL.Patient with no previous specific treatment for HLH syndromeFor patients of childbearing age : using an effective method of contraception during the trial, and through to 90 days after EOS for male participants and 30 days after EOS for female participantsFreely given, informed and written consent of legal representative of the participant or consent of the adult participantAffiliation to Social Security.Exclusion CriteriaPrevious treatment with ATG, Alemtuzumab, Etoposide, JAK-inhibitors, rifampicin and/or anti-Interferon gamma antibodies. St. John's Wort, or any other strong CYP3A4 inducers.Previous treatment with corticosteroids and/or cyclosporine A for more than 14 daysIsolated CNS disease.Contraindication to receive Ruxolitinib:History of hypersensitivity to the active substance or to any of the excipientsPregnant or lactating female patientContraindication to receive methylprednisolone or prednisoloneHistory of hypersensitivity to the active substance or to any of the excipientsAny infectious condition with the exception of infections, which are the trigger for lymphohistiocytic activation.Patient with acute very severe renal impairment (Creatinine Clearance <15 mL/min/1.73m²) who are NOT receiving dialysis.Patient with Grade 4 hepatic failure according to the CTCAE v5.0 of 27 November 2017 (Life-threatening consequences; moderate to severe encephalopathy; coma)Past or know active tuberculosisKnown rheumatologic disorder.Known active malignancy.Patient who is taking another investigational agent or is enrolled in another treatment protocol.Patient who cannot tolerate administration of drugs PO or through NG