Ruxolitinib-Enhanced Haplo HCT for Children and Young Adults With Sickle Cell Disease

Inclusion Criteria: 1. Participants with any genotypic form of SCD aged 12 - 45 years at enrollment with ≥1 of the following: 1. History of stroke and/or vasculopathy, including evidence of asymptomatic cerebrovascular disease for pediatric patients. 2. Recurrent moderate-severe acute chest syndrome (ACS) 3. Recurrent vaso-occlusive pain episodes requiring parenteral analgesia despite the institution of supportive care. 4. Need for chronic transfusion therapy to prevent vaso-occlusive complications (i.e. pain, stroke, and ACS). 5. For adult patients, an echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥ 2.7 m/sec. 2. Participants must have an HLA haploidentical first degree relative (parent, sibling, or half sibling) who is willing and able to donate bone marrow. 3. Participants must meet institutional eligibility criteria for HCT. Exclusion Criteria: 1. Presence of an HLA-matched sibling who is willing and able to donate bone marrow. 2. Uncontrolled infection, evidence of active TB, Hepatitis B or C infection, or HIV seropositivity or infection. 3. Previous HCT or solid organ transplant. 4. CNS revascularization procedure, myocardial infarction, pulmonary embolus or deep vein thrombosis in the past 6 months. 5. Use of medications which significantly interfere with ruxolitinib metabolism. 6. Known hypersensitivity or severe reaction to ruxolitinib or any component of the conditioning regimen or its excipients. 7. Inability to swallow and retain oral medication (use of nasogastric or gastrostomy tube permitted). 8. History of malignancy except resected basal cell carcinoma or treated carcinoma in-situ. 9. Participation in another clinical trial involving an investigational or off-label use of a drug or device in the past 3 months. 10. Currently pregnant or breast feeding. 11. Clinically significant, uncontrolled autoimmune disease. 12. High-titer anti-donor specific HLA antibodies (without review and approval by Study Chair). 13. Participant (or guardian) inability or unwillingness to comply with the dose schedule and study evaluations, comprehend or sign informed consent and utilize a highly effective method of contraception (for participants of child-bearing potential). 14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, pose a significant risk to the subject, or interfere with interpretation of study data.