Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment

Abstract

Background:Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported.Methods:We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months.Results:Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR.Conclusion:The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.

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 growthin vitroandin 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, 22–25]. 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.…”

“…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 graft-versus-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]. Taken together, these findings indicate that allogeneic stem cell transplantation may not be sufficient to control cancer by itself, but may serve as platform or model for immunotherapeutic approaches.…”

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.…”

“…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]. Taken together, these findings indicate that allogeneic stem cell transplantation may not be sufficient to control cancer by itself, but may serve as platform or model for immunotherapeutic approaches.…”