The Safety and Efficacy of Prophylactic Defibrotide Administration in Children, Adolescents, and Young Adults With Sickle Cell Disease or Beta Thalassemia Following Myeloablative Conditioning (MAC) and Haploidentical or Matched Unrelated Donor (MUD) 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 or MUD 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
• 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 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.
• all patients must meet disease, age, organ function and donor criteria;