Study of Ruxolitinib for Acute and Chronic Graft Versus Host Disease

ARM 1 Inclusion Criteria: * Established diagnosis of chronic GVHD (all grades eligible) * Currently on treatment with ruxolitinib for chronic GVHD for a minimum of 3 weeks * No changes in doses of ruxolitinib or concurrent azoles (if present) one week prior to obtaining ruxolitinib levels * Ages eligible for enrollment (0-≤18 years at time of enrollment) Exclusion Criteria: * Clinical presentation resembling overlap syndrome with both acute and chronic GVHD features ARM 2 Inclusion Criteria: * Ages \<12 years status post allogeneic hematopoietic stem cell transplant or solid organ transplant * Any underlying diagnoses, preparative regimen, stem cell source or acute GVHD prophylaxis are eligible * Diagnosis of acute GVHD which is refractory to steroids (defined as lack of improvement to 2 mg/kg/day of methylprednisolone or bioequivalent oral steroids, for 7 days or progression of acute GVHD within 72 hours at 2 mg/kg/day of Methylprednisolone or bioequivalent oral doses) * Able to take enteral medications * Clinically diagnosed Grades II to IV acute GVHD as per modified Glucksberg criteria occurring after allogeneic HSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with acute GVHD is encouraged but not required for study enrollment. * Blood counts at decision to initiate ruxolitinib: absolute neutrophil count (ANC) \> 1000/mm3\* AND platelets ≥ 20,000/mm3 (\*Use of growth factor supplementation and transfusion support is allowed to achieve these above defined hematological parameters) * Estimated GFR by cystatin C of \>30 mL/min * Prior systemic treatments for acute GVHD are allowed. Once ruxolitinib is initiated, no further doses of these agents will be allowed. * Calcineurin inhibitors are allowed throughout the duration of study and may be discontinued per treating physician discretion. Additionally dose adjustments to maintain target blood levels of calcineurin inhibitors may proceed per routine clinical practice. Exclusion Criteria: * Clinical presentation resembling de novo chronic GVHD or GVHD overlap syndrome with both acute and chronic GVHD features * Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. * Evidence of uncontrolled viral reactivation (Adenovirus, CMV, EBV, BK virus). If patients are on appropriate antiviral therapy or have received virus specific T-cells (either donor derived or third-party) then the viral reactivation is not considered uncontrolled. * Presence of relapsed primary malignancy. ARM 3 Inclusion Criteria: * 0-≤18 years of age are eligible * Any underlying diagnosis, preparative regimen, stem cell source or prior acute GVHD prophylaxis are eligible * Diagnosis of chronic GVHD as per 2014 NIH consensus criteria (any organ involvement is eligible) * Any GVHD global severity is eligible * Patients may have received methylprednisolone or oral bioequivalent steroids at a dose of 1 mg/kg/day (or greater) for up to 28 days prior to enrollment but may be enrolled anytime between diagnosis of chronic GVHD and day 28 of systemic steroids * Concurrent local therapies ( including but not limited to topical steroids, topical calcipotriene, ocular drops such as restasis, autologous serum eye drops, artificial tears, triamcinolone ointment for vulvar GVHD, Fluticasone Azithromycin and Singulair) are allowed at anytime while on ruxolitinib . Additional therapies may also be considered with PI review and approval * As children may not meet criteria for lung GVHD due to inability to perform PFTs we will establish the diagnosis of lung GVHD for children as defined by any of the following criteria listed below. However, the participants do not need to have lung involvement to be eligible to receive ruxolitinib. 1. \>10% decrease in FEV1 or FVC from baseline or 25% of FEF 25-75 2. Active GVHD in another organ system + pulmonary symptoms (Tachypnea without wheezing, new oxygen requirement, cough) 3. Increased R5 by 50% by Impulse oscillometry 4. Air trapping on high resolution CT scan, small airway thickening, or bronchiectasis in the absence of infection * Negative urine or serum pregnancy test for females of childbearing age * Estimated GFR by cystatin C \> 30 mL/min * Able to take enteral medications Exclusion Criteria: * Clinical presentation resembling overlap syndrome with both acute and chronic GVHD features * Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. * Evidence of uncontrolled viral reactivation (Adenovirus, CMV, EBV, BK virus). If patients are on appropriate antiviral therapy or have received virus specific T-cells (either donor derived or third-party) then the viral reactivation is not considered uncontrolled. * Presence of relapsed primary malignancy.