Sickle Cell Disease Transplant Using a Nonmyeloablative Approach: Adding Daratumumab for Patients With Anti-donor Red Cell AntibodY
This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.
⁃ General:
• Patients with SCD age 2-24.99 years who have a healthy HLA-identical sibling donor with major ABO incompatibility OR patients with RBC alloantibodies against other donor RBC antigens.
• Patients must have an absolute neutrophil count of 1 x 109/L and a platelet count of 100 x 109/L.
• Lansky/Karnofsky score of, at least, 70.
⁃ Patients with genotypes hemoglobin SS and Sβ0 thalassemia must have at least one of the following:
• History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a minimum of two separate occasions.
• Progression of CNS vasculopathy on MRA determined to be secondary to SCD.
• History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2-weighted images).
• History of two or more episodes of Acute Chest Syndrome (ACS) in lifetime.
• History of three or more SCD pain events requiring treatment with an opiate or IV pain medication in lifetime.
• History of any hospitalization for a complication secondary to SCD (does NOT include empiric hospitalizations for fever only).
• History of two or more episodes of priapism.
• Administration of regular RBC transfusions (≥8 transfusions episodes in the previous 12 months).
• At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.
⁃ Patients with all other sickle genotypes (e.g. hemoglobin SC, Sβ+ thalassemia, etc.) must have at least one of the following:
• Clinically significant neurologic event (overt stroke).
• History of two or more episodes of ACS in the 2-year period preceding enrollment.
• History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the 1-year period preceding enrollment.
• History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment.
• History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
• Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months)
• At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.