Inclusion
Subject with idiopathic hypereosinophilic syndrome must meet the following:
Has as at least 2 readings with an absolute eosinophil count \>= 1,500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
Dependent, intolerant or refractory to corticosteroids OR has relapsed/refractory disease to other therapy besides corticosteroids.
Symptomatic from his/her disease OR has one or more signs of organ damage (assessed by the investigator as possibly-related to eosinophilia or biopsy-proven). This can include skin, lung, cardiac, central nervous system, liver, or gastrointestinal (GI) involvement, or evidence of symptomatic hepatic or splenic enlargement.
Subject with lymphocyte-variant hypereosinophilia must meet the following
Has at least 2 readings with an absolute eosinophil count \>= 1,500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
Dependent, intolerant or refractory to corticosteroids\* OR has relapsed/refractory disease to other therapy besides corticosteroids.
Symptomatic from his/her disease OR has one or more signs of organ damage (assessed by the investigator as possibly-related to eosinophilia or biopsy-proven). This can include skin, lung, cardiac, central nervous system, liver, or GI involvement, or evidence of symptomatic hepatic or splenic enlargement
Has abnormal T-lymphocyte immuno-phenotype by flow cytometry.
Subject with chronic eosinophilic leukemia, not otherwise specified (CEL,NOS) must meet the following
Has at least 2 readings with an absolute eosinophil count \>= 500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
Newly-diagnosed OR receiving corticosteroids OR has relapsed/refractory disease to any therapy besides corticosteroids.
Has increased blasts in the blood or bone marrow (\> 5% and \< 20%), and/or a clonal cytogenetic or molecular abnormality
Subjects with JAK2 mutations are included within this group.
Subject with JAK2-rearranged eosinophilic neoplasm must meet the following
Has at least 2 readings with an absolute eosinophil count \>= 500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
Newly-diagnosed OR receiving corticosteroids OR has relapsed/refractory disease to any therapy besides corticosteroids.
This group includes subjects with PCM1-JAK2, BCR-JAK2, ETV6-JAK2 or other JAK2 rearrangements.
If receiving corticosteroids, must be a stable dose for \>= 28 days prior to Day 1 (unstable dosing not eligible).
Eastern Cooperative Oncology Group (ECOG) performance status =\< 3.
Willing and able to review and execute informed consent (legally-authorized consent acceptable).
Exclusion
Active life-threatening complication(s) from underlying eosinophilic disease (i.e., leukostasis; acute thromboembolic disease including central nervous system (CNS) involvement; severe pulmonary or cardiac dysfunction). Stabilization of acute, life-threatening eosinophil-related co-morbidities will allow enrollment of the patient.
World Health Organization (WHO)-defined myeloid neoplasm associated with eosinophilia other than CEL NOS and JAK2 rearranged neoplasms (e.g., myelodysplastic syndrome (MDS); myeloproliferative neoplasms (MPN); MDS/MPN overlap disorders; and systemic mastocytosis (SM).
Reactive hypereosinophilia due to connective tissue disease, sarcoidosis or eosinophilic granulomatosis with polyangiitis.
Organ-restricted ?tissue? eosinophilia with the absence of peripheral eosinophilia in the blood.
Invasive malignancy over the previous 2 years except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers.
Myeloid or lymphoid neoplasm with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1.
Anticipated to receive a hematopoietic stem cell transplant within the first 6 months of treatment on trial.
Major surgery within 4 weeks prior to entering the study.
Life expectancy of \< 6 months.
Known diagnosis of human immunodeficiency virus (HIV).
Known diagnosis of chronic active hepatitis B or C (viral testing is not required). Subjects with a known history of hepatitis B and/or C are allowed on trial if at the time of enrollment, the virus is not active and undetected (testing required if there is a known history), and such patients are not actively receiving antiviral treatment specific for hepatitis B and/or C.
Clinically serious infections requiring ongoing antibiotic therapy.
Parasitic infection diagnosed within 24 weeks prior to enrollment.
Platelet count =\< 25 x 10\^9/L at baseline.
Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) \> 4 x upper limit of normal (ULN) or direct bilirubin \> 4 x ULN (if considered to be unrelated to the underlying eosinophilic disorder).
End-stage renal function (creatinine clearance \[CrCl\] \< 15 mL/min or glomerular filtration rate \[GFR\] \< 15 mL/min) regardless of whether hemodialysis is required.
Use of investigational or commercial therapies with the intent to treat the underlying eosinophilic disorder within 28 days of study start, including interferon; imatinib; alemtuzumab; cyclosporine; methotrexate; mepolizumab; benralizumab; or other antibody therapies.
Use of hydroxyurea within 7 days of study start.
Prior therapy with ruxolitinib or other JAK inhibitors.
Previous allergic reactions to JAK inhibitors or excipients.
Unwilling to commit to abstinence from heterosexual contact or agree to use and comply with highly effective contraception, 28 days prior to starting study drug, during the treatment period and for 12 weeks after discontinuation of study treatment.
Females of childbearing potential who have a positive pregnancy test (urine or serum) during screening period.