Donor Lymphocyte Infusion Prevented Late Post-Transplant Rejection in 30 Patients with Thalassemia Major

OBJECTIVE:To investigate the role of donor lymphocyte infusions (DLI) in preventing post-transplant graft rejection (GR) in hematopoietic stem cell transplantation (HSCT) for patients with β-thalassemia major (TM);

METHODS: A total of 50 patients with TM who had mixed chimerism (MC) after HSCT from June 2011 to June 2016 was divided into 4 groups. The group 1 included the patients with grade I MC ratio of 90%-95% (n=20) but not DLI; Group 2 patients had same grade I MC ratio as Group 1 and received DLI (n=11); Group 3 had grade II MC ratio of 75%-90% (n=13); Group 4 had grade III MC of <75% (n=6). Group 1 received gradually reduced immunosuppressive agents; Groups 2 to 4 received DLIs of gradually increasing dose after reduction of immunosuppressive agents;

RESULTS: (1) Full donor chimerism (FDC) conversion rates in the groups 1 to 4 were 100%, 100%, 85%, and 66.7%, respectively; The incidence of graft versus host disease (GVHD) in groups 1 to 4 was 15%, 27.3%, 46.2%, and 33.3%, respectively; (2) There was no significant differeces as comparing incidence of GVHD in group 1 and in group 2 (15% vs. 27.3%, P = 0.638); (3) A significant difference was found in comparing patients receiving initial DLI at ≤180 and > 180 days and the incidence of GVHD was 50% vs 10% (P=0.049); (4) Comparing the accumulated doses of DLI >1×107/kg with ≤1×107/kg, the incidence of GVHD was 50% vs. 27.3% (P=0.142);

CONCLUSION: 1. The optimal choice for post-transplant MC grade 1 patient is only observation and decreasing the immunosuppressive drugs; 2. For grade 2-3 patients with high risk of rejection, the fractional increasing dose DLI can effectively reverse the unstable chimera to FDC; 3. Post-DLI GVHD was associated with DLI timing, and the incidence of GVHD was higher in patients who received DLI at ≤180 days after transplantation.