No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients

Abstract

transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts.Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts.Results: Median overall survival was 7.9 months [61.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (61.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE).Conclusions: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.

Transgenic antigen-specific, HLA-A*02:01-allo-restricted cytotoxic T cells recognize tumor-associated target antigen STEAP1 with high specificity

“…40,41 Further, there was no improvement of survival of ES patients receiving reduced intensity conditioning compared to high-dose conditioning prior to allogeneic SCT with HLA-matched grafts, implicating absence of a clinically relevant graft versus ES effect. 42 T-cell recognition of conventional and allogeneic antigens share similarities. 43,44 Allo-restricted T cells mainly recognizing peptide in the context of specific MHC, are now easily isolated from an allogeneic T cell population by the use of peptide MHC multimers.…”

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

“…The major cause of death still is relapse followed by transplant-related toxicity, post transplant infections and GvHD. 10,11 In mismatched haploidentical transplantation, natural killer (NK) cells have been shown to exert significant GvL effects in the presence of KIR ligand incompatibility in GvH direction. 12,13 In pediatric solid tumors, this has also been observed in a limited number of patients.…”

Human HLA-A*02:01/CHM1+ allo-restricted T cell receptor-transgenic CD8+ T cells specifically inhibit Ewing sarcoma growth in vitro and in vivo

“…Some reports indicate that the lessons learned from immunotherapy of melanoma patients could be potentially translated to other solid tumor entities [9]. However, in the pediatric sarcoma setting, tumor immunogenicity remains yet to be determined [4,6,13,14,[22][23][24][25]. The possibility to target tumor cell antigens essential for survival and proliferation, including transcription factors such as CHM1 renders the use of peptide specific T cells is very attractive.…”

“…Wells were blocked with 2% BSA in PBS for 1 h at 37°C and then washed twice with 2.5% HEPES in PBS. Stimulated PBMCs/T-cells were collected and set to a concentration of 1x10 6 / ml in TCM. 1 ml of each Virus supernatant and T cells were added into coated 6-well plates with additional Protamine-sulfate (c end = 4 μg / ml), HEPES (c end = 0.5%), and IL-2 (c end = 100 U / ml).…”

“…Koscielniak et al [10] and Lucas et al [11] reported on AES patients who experienced tumor regression upon allogeneic stem cell transplantation. In recent analyses on the role of allogeneic stem cell transplantation in the treatment of AES patients we demonstrated high treatment toxicity due to graft versus host disease (GVHD) but absence of a graftversus-ES effect in HLA-matched settings [12,13]. In a further analysis we demonstrated tumor control in several patients with rhabdomyosarcoma who received unspecific donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation [14].…”