Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH)

Inclusion Criteria: * Ability to understand and the willingness to sign a written informed consent document. * Males and females, 18 years of age or older at the time of enrollment. * Participants must have active HLH and meet \>= 5 of 8 of the HLH-2004 diagnostic criteria, or have familial/primary HLH with pathogenic/likely pathogenic germline variant(s) in genes known to cause HLH (e.g., PRF1, UNC13D, Syntaxin 11 (STX11), Syntaxin-binding protein 2 (STXBP2), RAB27A, SH2 domain-containing protein 1A (SH2D1A), baculovirus inhibitor of apoptosis repeat containing protein 4 (BIRC4), Lysosomal trafficking regulator (LYST), interleukin-2-inducible T-cell kinase (ITK), SLC7A7, X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN), Hermansky-Pudlak syndrome (HPS), NLR family CARD domain-containing protein 4 (NLCR4) or other immune regulatory genes. * Fever \>= 38.5 degrees Celsius (C) (or \>= 38 degrees C if acetaminophen given in prior 6 hours). * Splenomegaly. * Peripheral cytopenias involving \>= 2 of 3 cell lines (absolute neutrophil count \< 1000/uL; hemoglobin \< 9 g/dL; platelets \< 100,000/uL). * Hypertriglyceridemia (fasting triglycerides \>= 265 mg/dL) or Hypofibrinogenemia (fibrinogen =\< 150 g/dL). * Hemophagocytosis on tissue biopsy, such as in the bone marrow, spleen, lymph node, or liver. * Low/absent natural killer (NK)-cell activity/perforin and/or decreased CD107a mobilization. * Ferritin \>= 500 ug/L. …