Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease (NYMC-571)

This is an interventional treatment trial for Sickle Cell Disease focused on measuring stem cell transplantation, sickle cell disease, haploidentical, defibrotide Read More

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;

Exclusion 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