Complementary Transplantation Improved Results of Both Peripheral Blood Stem Cells and Unrelated Cord Blood Transplants in Thalassemia: A Multi-Center Study from China

Abstract

Background: Unrelated cord blood (UCB) transplant (UCBT) is not recommended in patients with thalassemia major (TM) so far. Post-transplant (PT) Cyclophosphamide (PTCy) with long pre-transplant immunosuppression therapy have improved haploidentical peripheral blood (PB) stem cell transplant (haplo-SCT) survival in TM patients but with 2/31 primary rejection. So, we designed a novel dual transplantation of UCBT following haplo-SCTwith PTCy(NF-14-TM-CT protocol). Aim:To improve results of haplo-SCT and UCBT in patients with TM. Patients and method: NF-14-TM -CT protocol was termed as double-insurance dual transplantsincluding a haplo-SCT and an UCBT, in which conditioning regimen consisted of ATG (at -10 to -8 day), Cy (-7), Fludarabine (-6 to -2), Busulfan (-6 to -4) Thiotepa (-3), haplo-PB (0), PTCy (+3, +4) and UCB (+6). PTCy serve as GVHD prophylaxes after haplo-SCT and as conditioning before UCBT. In total 131 patients with TM from three pediatric center in China received NF-14-TM-CT protocolfrom June, 2014 to April, 2019, with a median follow-up of 13 (2-59) months and a median age of 8 (3.5-17) years. Results Final haplo-PB engrafted(group1)in 76 patients with mean PBSC-MNCof 22.49 (±5.36) x108/kgand UCB nuclear cells (NC) of 5.95 (±3.39) x107/kg and final UCB engrafted (group 2) in 55 patients with mean PBSC-MNC of 21.78 (±5.68) x108/kg and mean UCB-NC of. 5.43 (±2.32) x107/kg. The 4-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR), and transplant related mortality (TRM) were 97.6%, 96.0%, 1.5%, and 2.4%, respectively (Fig. A), in total. The corresponding rates for group 1 were 98.3%, 96.9%, 1.7% and 1.8% and for group 2 were 95.5%, 93.8%, 4.5% and 1.4%, respectively. No statistic significant difference was found in OS, TFS, GR and TRM, respectively, when comparing group 1 with group 2 (Fig. B. C, D, E).The incidence of grade II-IV acute GVHD, III-IV acute GVHD, mild chronic GVHD, moderate/severe chronic GVHD, VOD, PT cystitisand PT hemolysis of the entire cohort was 16.8%, 6.87%, 9.92%, 1.52%, 4.60%, 31.3% and 14.5, respectively. Summary:Current study proved that the novel CT improved the results of haplo-SCT and UCBT in patients with TM. Disclosures Wing: Miltenyi Biotec: Employment.

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children’s patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study

“…High MNC of PBSC from relative donors combined with unrelated CB were applied. And PTCY with or without a low dose of ATG rather than a regular dose of ATG in vivo T cell depletion in haplo-HSCT in our study (Li et al, 2019;Xiao et al, 2021). Consistently, a series of studies support CMV infection occurred more frequently in haplo-HSCT due to delayed T-cell reconstitution (Dziedzic et al, 2017;Lin et al, 2019;Yokoyama et al, 2019;Solano et al, 2021;Cho et al, 2021).…”

“…The donor selection and the transplant protocol were administered as previously reported ( Li et al., 2012 ; Li et al., 2019 ; He et al., 2020 ; Xiao et al., 2021 ; Wen et al., 2022 ). In brief, a myeloablative conditioning regimen like busulfan (Bu)/cyclophosphamide (Cy)/fludarabine (Flu) with or without thiotepa (TT) was used for HLA-matched relative or unrelative donor transplant with anti-thymocyte globulin (ATG) as in vivo T cell depletion.…”

Applying Rituximab During the Conditioning Regimen Prevents Epstein–Barr Virus Infection Following Allogeneic Hematopoietic Stem Cell Transplant in a Children’s Cohort: A Retrospective Case–Control Study

“…The conditioning regimens were depicted in previous studies [ 14 – 17 ]. Briefly, the myeloablative conditioning regimens consisted of busulfan/cyclophosphamide/fludarabine with or without thiotepa.…”