Ruxolitinib for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (RISE)

Inclusion Criteria: * Patients of age 18 or older * Diagnosis of for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) per ASTCT consensus criteria * Patients must have an elevated ferritin (\>2 × ULN) at time of infusion and/or have a ferritin count that is rapidly rising (per clinical assessment) and at least 2 of the following manifestations as described in the ASTCT consensus criteria: * Onset with resolving/resolved CRS or worsening inflammatory response after initial improvement with CRS-directed therapy * Hepatic transaminase elevation§ (\>5 × ULN (if baseline was normal) or \>5 × baseline if baseline was abnormal) * Hypofibrinogenemia (\<150 mg/dL or \<LLN) * Hemophagocytosis in bone marrow or other tissue * Grade 1 cytopenias (new onset, worsening, or refractory) defined as: * Anemia (Hgb) \<LLN\* - 10.0 g/dL(gr1) * Neutropenia (ANC) 1,000 - 1,499/µL (Gr1) * Thrombocytopenia \<LLN - 75,000/µL (Gr1) * Lactate dehydrogenase elevations (\>ULN) * Other coagulation abnormalities (e.g. elevated PT/PTT) * Direct hyperbilirubinemia * New-onset splenomegaly that is palpable ≥5 cm below costal margin or \>450cc on imaging * Fever of 100.4 or greater (new or persistent) * Neurologic changes greater than baseline that are consistent with a grade 1 Immune Effector Cell Encephalopathy (ICE) Score or greater * Pulmonary manifestations * Gr 2 Hypoxia with decreased oxygen saturation with exercise (e.g. pulse ox \<88%) * pulmonary infiltrates * pulmonary edema with radiologic findings and moderate dyspnea on exertion * New onset renal insufficiency defined by: * an absolute increase in serum creatinine of ≥0.3 mg/dL within 48 hours. * A baseline increase in serum creatinine of ≥1.5 times within the prior 7 days. * Oliguria defined as urine volume \<0.5 mL/kg/h for at least 6 hours. * Hypertriglyceridemia (fasting level, \>265 mg/dL‖) * Patients who have received a CAR T product, commercially available or investigational, will be allowed to enroll * Eastern Cooperative Oncology Group (ECOG) Performance Score43 of 0-2 * Patients may be treatment naïve for the IECH-HS diagnosis or may have received prior or ongoing treatment. Corticosteroids can be continued along with RUX initiation as noted above. * Patient is able to take oral medication or is willing to have an NG tube placed if unable to take oral medication. Patients in whom NG tube was placed due to acute decompensation (resulting in an ECOG of \>2), will be excluded. * Willing and able to sign an informed consent form Exclusion Criteria: * Life expectancy greater than 6 months * Patients with known active malignancy or known progressive underlying disease * Women who are pregnant or breastfeeding. Women must also refrain from breastfeeding during the course of study and for 60 days after the last dose of study treatment. * Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. Participants with acute infection requiring antibiotic, antifungal, or antiviral treatment use should delay screening/enrollment until the course of antibiotic antifungal, or antiviral therapy has been completed and the infection is not active anymore. Note: If a participant has a positive screening test result for SARS-CoV-2 infection, the participant should be excluded until test normalization and clinical recovery. * Any prior investigational agent used to treat IEC-HS * Patient on treatment with rifampin, St Johns wart or other JAK inhibitors * Patient is unable to tolerate medicine administration either orally or via NG tube. * Known history of allergic reaction to ruxolitinib * History of clinically significant or uncontrolled cardiac disease, including recent (within the last 12 months) unstable angina or acute myocardial infarction, or New York Heart Association Class III or IV congestive heart failure, or clinically significant arrhythmias not controlled by medication. Participants with a pacemaker and well-controlled rhythm for at least 1 month before the first dose of study treatment will be allowed. * Any major surgery within 28 days before the first dose of study treatment. * Active HBV (or at risk of reactivation), defined as follows: positive HBsAg result (laboratory test required at screening), and/or positive total anti-HBc result (laboratory test required at screening), and/or quantitative HBV DNA test result greater than the lower limits of detection of the assay (if known; laboratory test not required for eligibility purpose, but can be done as part of screening if available locally). Note: Participants with no prior history of HBV infection who have been vaccinated against HBV and who have a positive anti-HBs as the only evidence of prior exposure may participate in the study. * Active HCV, defined as follows: positive anti-HCV result (laboratory test required at screening) and quantitative HCV RNA test result greater than the lower limits of detection of the assay (laboratory test only required if anti-HCV-positive, can be done as part of screening if available locally). Note: Anti-HCV-positive participants who received and completed treatment for HCV that was intended to eradicate the virus may participate if HCV RNA levels are undetectable at least 12 weeks after the last dose of therapy. Anti-HCV-positive participants with no available confirmatory negative HCV RNA test results will be excluded. * Known history of HIV (1/2 antibodies). * Any condition or circumstance that would, in the investigator's judgment, interfere with full participation in the study (eg, unable, unlikely, or unwilling to comply with the dose schedule and study evaluations, active alcohol or drug addiction), including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.