Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease
This multisite prospective study seeks to determine if HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus (Sickle transplant Using a Nonmyeloablative approach, SUN) can decrease the toxicity of transplant while achieving a high cure rate for children with sickle cell disease (SCD).
⁃ 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 (or ≥185 cm/sec by the imaging technique) measured at a minimum of two separate occasions.
• 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 (inpatient or outpatient) in lifetime.
• 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.
⁃ Patients with all other sickle genotypes (hemoglobin SC, Sβ+ thalassemia) 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-years 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.