The purpose of this study is to find out what effects ruxolitinib in combination with a deintensified

HLH-94 drug regimen has on patients with newly diagnosed hemophagocytic

lymphohistiocytosis (HLH), a disorder caused by dysregulated immune responses (that

is, immune responses that are too strong and cause inflammatory damage to normal

tissues). The therapy used for HLH decreases the activity of the immune system.

All patients in this study will be given a de-intensified HLH-94 regimen and ruxolitinib.

De-intensified HLH-94 is a treatment regimen that includes 4 weeks of dexamethasone

with the dose being decreased each week, and up to 4 weeks of etoposide. This

combination is commonly used to treat HLH. Dexamethasone is a steroid medication

that works by fighting inflammation. Dexamethasone can be taken orally (by mouth) or

infused into a subjects veins. Etoposide is a type of chemotherapy (a cancer medicine) that is

used to kill the types of white blood cells in HLH that are attacking a subjects body. Etoposide

is given as an infusion. Both dexamethasone and etoposide are FDA-approved.

Ruxolitinib is a type of drug called a kinase inhibitor. It works by blocking the signals that

cause inflammatory cells to multiply. Ruxolitinib is FDA approved for other diseases and

conditions, but its use is considered investigational for HLH (not FDA-approved).

Ruxolitinib is an oral medication.