A study of patients with symptomatic sickle cell disease (SCD) who underwent CD34+ cell-selected, T-cell-depleted peripheral blood HCT from a mismatched family member or unrelated donor has resulted in a 2-year overall survival rate of 90%.
Ten patients received a reduced-intensity conditioning regimen (melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin), with the goal of decreasing late adverse effects.
At a median follow-up of 49 months (range, 14-60), 9 of 10 patients were alive, and had stable donor hematopoietic engraftment (mean donor chimerism, 99.1% ± 0.7%). Seven patients received post-HCT donor lymphocyte infusions (DLI) in a companion study to improve immune recovery.
Hematopoietic cell transplantation resolved all surviving patients’ sickle cell complications. Two patients experienced grade II-IV acute GVHD following prophylactic and therapeutic DLI, and one patient who experienced acute GVHD developed chronic GVHD.
Epstein-Barr virus-related post-transplant lymphoproliferative disorder (PTLD) occurred in 3 patients, and one patient died as a consequence of treatment of PTLD.
The researchers concluded that despite the high rate of PTLD, “successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD.”
Gilman AL, et al. Blood Advances