Ruxolitinib Based GVHD Prophylaxis Regimen before, during, and after Hematopoietic Cell Transplantation in Older Adult Patients with Acquired Aplastic Anemia

Inclusion Criteria

• Age > 40 years or ages 18 - 40 years with Hematopoietic Cell Transplantation - Specific Comorbidity Index (HCT-CI) score > 3 necessitating a low intensity transplant or determined inability to tolerate antithymocyte globulin (ATG) (Sorror M JCO 2014)
• Diagnosis of severe acquired aplastic anemia defined as a bone marrow hypoplasia (< 25% or 25-50% with < 30% residual hematopoietic cells) shown by a biopsy and at least two of the three following criteria: absolute neutrophil count (ANC) < 0.5×10^9/L, platelets < 20×10^9/L, or absolute reticulocytes < 40×10^9/L or
• Non-severe acquired aplastic anemia defined as a hypocellular marrow and transfusion dependent (red cells and/or platelets)
• Does not meet World Health Organization (WHO) criteria for myelodysplastic syndrome (MDS)
• Ability to understand and the willingness to sign a written informed consent document
• Patient must be a potential hematopoietic stem cell transplant candidate as assessed by the consenting physician
• Karnofsky ≥ 70
• Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hr urine creatinine clearance must be > 60 ml/min
• Total serum bilirubin must be < 2 mg/dL unless the elevation is thought to be due to Gilbert’s disease or hemolysis
• Transaminases must be < 3x the upper limit of normal
• Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded
• Diffusing capacity for carbon monoxide (DLCO) corrected > 60% normal
• May not be on supplemental oxygen
• Left ventricular ejection fraction > 40% OR shortening fraction > 26%
• Patients may have received prior treatment for their AA but they are NOT required to have received immune suppression prior to consideration for transplant

Exclusion Criteria

• Contraindication to receiving ruxolitinib including: patients who have known hypersensitivity to JAK inhibitors and excipients
• Patients with history of myocardial infarction (MI), cerebrovascular accident (CVA) or unprovoked pulmonary embolism (PE)/deep vein thrombosis (DVT) in past 6 months
• History of prior allogeneic transplant
• Active or recent infection without infectious disease (ID) consult and approval
• History of untreated tuberculosis (TB)
• History of HIV infection
• Pregnant or breastfeeding
• History of prior malignancy with > 20% risk of recurrence in the next 5 years
• Patients without an HLA-identical sibling donor, 10 of 10 HLA-matched or 9 of 10 mismatched unrelated donor that meet transplant criteria