Unrelated Umbilical Cord Blood Transplantation for Sickle Cell Disease Following Reduced-Intensity Conditioning: Results of a Phase I Trial.
Hematopoietic stem cell transplantation from HLA-matched sibling donors results in disease-free survival of >90% in patients with sickle cell disease (SCD); however, only approximately 18% of these patients have suitable donors available. Unrelated cord blood transplantation (UCBT) is one way to expand donor options for patients with severe SCD, but historically has been associated with high graft rejection rates (50% to 62%). We hypothesized that the addition of thiotepa to a previously tested reduced-intensity conditioning (RIC) regimen would support engraftment after UCBT in patients with SCD. Nine children (age 3 to 10 years) with cerebrovascular complications of SCD underwent 5-6/6 HLA-matched (A, B, and DRB1 loci) UCBT after conditioning with hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan. A calcineurin inhibitor and mycophenolate mofetil were used for graft-versus-host-disease (GVHD) prophylaxis. With median follow up of 2.1 years (range, 1 to 4.2 years), 7 patients had sustained donor cell engraftment and are free of SCD, and 2 patients had autologous recovery. Acute GVHD (grade II-IV) and mild and moderate chronic GVHD developed in 3 patients, 2 patients, and 1 patient, respectively. At >2 years post-UCBT, 4 of 5 patients discontinued systemic immunosuppression. Seven patients had viral infections (cytomegalovirus, Epstein-Barr virus, respiratory syncytial virus, or adenovirus) and recovered. The 1-year overall survival and disease-free survival rates were 100% and 78%, respectively. Thus, this RIC regimen was able to achieve donor engraftment in the majority of patients. Future efforts will focus on further reducing rates of acute GVHD and viral infection.
['Abraham|Allistair|A|', 'Cluster|Andrew|A|', 'Jacobsohn|David|D|', 'Delgado|David|D|', 'Hulbert|Monica L|ML|', 'Kukadiya|Divyesh|D|', 'Murray|Lisa|L|', 'Shenoy|Shalini|S|']
D000074323:Alemtuzumab D000755:Anemia, Sickle Cell D065095:Calcineurin Inhibitors D002648:Child D002675:Child, Preschool D036101:Cord Blood Stem Cell Transplantation D005260:Female D005500:Follow-Up Studies D006086:Graft vs Host Disease D006801:Humans D006918:Hydroxyurea D008297:Male D008558:Melphalan D009173:Mycophenolic Acid D016019:Survival Analysis D013852:Thiotepa D019172:Transplantation Conditioning D014184:Transplantation, Homologous D016896:Treatment Outcome D061349:Unrelated Donors D014740:Vidarabine
Sickle cell disease Stem cell transplant Unrelated cord blood