Preliminary Experience with Haploidentical Stem Cell Transplantation for Children with Sickle Cell Disease and Stroke.

Hematopoietic stem cell transplantation has been shown to be curative for approximately 83% of symptomatic children with sickle cell disease who have undergone the procedure. Despite these encouraging results, only 15% of children with symptoms that might merit consideration for transplantation have an available, unaffected HLA-matched sibling donor, severely limiting this therapeutic option. To address this problem, we developed a protocol for children with SCD and stroke using reduced-intensity conditioning and CD34-selected peripheral blood stem cells from haploidentical parental donors. We now report our preliminary experience using this approach in three children with SCD and stroke. After a chemotherapy-only conditioning regimen of fludarabine 150–200 mg/m², thiotepa 10 mg/kg, i.v. busulfan targeted to a steady state concentration of 900 ng/ml, and OKT3, patients received an average of 27.2 x 10⁶ CD34⁺cells/kg and 1.1 x 10⁴ CD3⁺ cells/kg. Two patients required additional immunosuppression with methylprednisolone and OKT3 followed by a CD34 boost after graft rejection. One of these two had durable long-term engraftment, while one had a second rejection. Two of three patients have durable donor engraftment 20 and 24 months after transplantation, respectively. Donor T-cell chimerism evolved from predominantly host-derived to donor-derived over a number of months. One patient developed grade I acute GVHD and none developed chronic GVHD. Two engrafted patients have had no further SCD events. Both have recovery of immune function with normal CD4⁺ T-cell counts and normal thymic function. This preliminary experience demonstrates the feasibility of using mismatched parental donors for children with sickle cell disease. Future studies will focus on achieving reliable donor engraftment through additional graft manipulation strategies.