Safety and Efficacy of Prophylactic Defibrotide in Children, Adolescents, and Young Adults With Sickle Cell Disease or Beta Thalassemia Following MAC and Haploidentical Stem Cell Transplantation Utilizing CD34 Enrichment and T-Cell (CD3) Addback
This is a follow-up trial to NYMC 526 (NCT01461837) to assess the safety, efficacy and toxicity of administering Defibrotide prophylaxis for high-risk sickle cell or beta thalassemia patients undergoing a familial haploidentical allogeneic stem cell transplantation with CD34 enrichment and T-cell addback. This patient population historically has a risk of developing sinusoidal obstructive syndrome (SOS) and Defibrotide has demonstrated efficacy in treatment of SOS. The Funding Source is FDA OOPD.
• 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;