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

Inclusion 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;