Double Donor Lymphocytes Infusion Reduced the Rejection in Tαβ Cell Depleted Hematopoietic Stem Cell Transplantation from Haploidentical Donors for Thalassemia Patients

Background and aim: Hematopoietic stem cell transplantation (HSCT) still was a cure way proved by time in patients with thalassemia major (TM), but it usually resulted in severe graft versus host disease (GVHD). Although low GvHD have been proved in Tαβ cell depleted HSCT (TDH) from haploidentical (haplo-) donors, rejection was high in TM patients. For preventing the high rejection, we tried to give the TM patients double donor lymphocytes infusion (DLI) in haplo-TDH.

Patients and method: Total 69 TM patients received haplo-TDH from April 2021 to July 2022 in Taixin BMT center. Median age was 8 (3-19) year old and male: female was 48:21. Conditioning regimen included ATG on -day 21 and 3-Gy TBI on -13 day, as well as, Cy-Bu-Flu-TT as NF-08-TM protocol. Prophylaxis of GVHD included short-term (< 6 months) Tacrolimus or Sirolimus with or without MMF. The mean doses of infused CD34+ cells, Tgd cells, and NK cells were, respectively, 32.51(14.3-61.2) *10⁶/kg, 37.34(5.18-137.59) *10⁶/kg, and 107.72(34.15-309.40) *10⁶/kg. Infused Tab dose was < 0.5*10⁵/kg. First DLI (2*10⁸/kg) on -day13 and second DLI (2*10^5/kg) on day 0.

Results: All patients excluded one got engraftment of 3-line blood cells in +day25 and platelet recovered usually at first. Overall survive (OS) was 100%, thalassemia-free survive (TFS) was 98.5% (Fig.1), with 136-day median follow-up. Primary engraftment failure occurred in one patient, who underwent second haplo-HSCT from alternative donor with post-transplant Cyclophosphamide after a reduced toxicity conditioning on +day 30 and acquired TFS. So, in total, TFS was 100% for 69 TM patients in the current study. No GVHD (acute and chronic) occurred in majority patients. Some patients have acute GVHD less than 2 degree and was cured soon.

Summary: Current study proved that double DLI reduced the rejection in haplo-TDH for TM patients.

No relevant conflicts of interest to declare.