Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease

Eligibility Criteria

• * Disease: Homozygous Hemoglobin S Disease, or Hemoglobin S B0/+ thalassemia, or Hemoglobin SC Disease, or Beta thalassemia intermedia/majora
• * Patients must demonstrate one or more of the following Sickle Cell Disease Complications (or patients in Cohort 2 can meet other high risk criteria instead)
• * Clinically significant neurologic event (stroke) or any neurologic deficit lasting \>24 hours that is accompanied by an infarct on cerebral MRI
• * Acute chest syndrome in the preceding two year period prior to enrollment that have failed, been non-compliant or declined hydroxyurea treatment, or prior to chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis.
• * Recurrent painful events (at least 3 in the 2 years prior to enrollment or prior to chronic chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis).
• * Abnormal TCD study requiring starting on chronic transfusion therapy and/or exchange transfusions.
• * At least one silent infarct lesion on a MRI scan of the head. Or (directly or probably related to SCD)
• * Sickle Cell nephropathy;
• * Splenic sequestration requiring RBC transfusion;
• * Aplastic crisis requiring RBC transfusion;
• * Avascular necrosis of the hip diagnosed by MRI;
• * Two episodes or more of leg ulcerations;
• * Recurrent priapism .
• * Infant dactylitis.
• * OR for Cohort #2 ONLY: Patient must be between 18 and 34.99 years of age, patients must demonstrate at least two of the following:
• * WBC \> 13,500 cells/microliter at baseline when not acutely ill (on two separate occasions) \> 2 weeks from a VOC event or hospitalization.
• * Tricuspid Regurgitant Jet Velocity (TRV) \> 3.0 m/s
• * Requiring Chronic Monthly Transfusions ( \> 12 transfusions in the 12 months)
• * History of sepsis
• * N-terminal pro-brain natriuretic peptide (NT-proBNP) \> 160 ng/L at clinical baseline when not acutely ill or hospitalized.
• * all patients must meet disease, age, organ function and donor criteria;
• * Patients who are receiving concomitant systemic anticoagulants and/or fibrinolytic therapies.
• * Patients with a previously known hypersensitivity reaction to defibrotide.
• * Females who are pregnant or breast-feeding are not eligible
• * SCD Patients with documented uncontrolled infection at the time of study entry are not eligible.
• * SCD patients who have an unaffected HLA matched family donor willing to proceed to donation will not be eligible for this study.
• * Karnofsky or Lansky (age appropriate) Performance Score \<50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
• * Demonstrated lack of compliance with medical care.
• * Patients with clinically significant fibrosis or cirrhosis of the liver will not be eligible.
• * Patients who have previously received a HSCT will not be eligible.
• * Patients with contraindications to the use of defibrotide