Stem Cell Transplantation With Identical Donors for Patients With Sickle Cell Disease

Allogeneic Stem Cell Transplantation From HLA/MLC Genotype Identical Donors for Patients With High Risk Sickle Cell Disease

This protocol studied the effect of administration of a myeloablative pretransplant preparative regimen followed by an infusion of donor stem cells in children with severe sickle cell disease. The donor graft consisted of bone marrow or cord blood derived from a genetically matched sibling.

The primary aim of the study was to evaluate how well the donated cells migrated to the bone marrow and begin producing healthy red blood cells, white blood cells and platelets (engrafted), how well the recipients immune system recovered, and assess any regimen related toxicities including a potentially life-threatening transplant related complication called graft-versus-host-disease or GVHD.

The secondary objectives of this protocol evaluated the effect of this transplant procedure on the subsequent clinical course of patients with severe SCD. Specifically, to determine whether pre-transplant organ dysfunction (brain, heart, lung, kidney, liver, spleen, etc) resultant from sickle hemoglobinopathy can be reversed following this particular transplant procedure.

Inclusion criteria:

Diagnosis of severe' disease is denoted by one of the following:

• Previous central nervous system vaso-occlusive episode with or without residual neurologic findings or
• Frequent painful vaso-occlusive episodes with significant interference with normal life activities and which necessitates chronic transfusion therapy or
• Recurrent SCD chest syndrome events which necessitate chronic transfusion therapy.

Exclusion criteria:

• Patient with SCD chronic lung disease greater than or equal to stage 3
• Patient with severe renal dysfunction defined as creatinine clearance < 40 ml/min/1.73m2.
• Patient with severe cardiac dysfunction defined as echocardiogram shortening fraction < 25%.
• Patient with HIV infection.
• Pregnant or lactating.
• Patient with unspecified chronic toxicity that in the opinion of the Principal Investigator is serious enough to detrimentally affect the patient's capacity to tolerate SCT.
• Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process