No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease

Abstract

Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).

Haploidentical hematopoietic stem cell transplantation as individual treatment option in pediatric patients with very high-risk sarcomas

“…Only 38% of patients achieved CR or VGPR prior to HSCT. The influence of pre-transplant remission status on survival has been reported earlier in patients with Ewing sarcoma ( 29 ). Indeed, in our cohort, patients who underwent haplo-HSCT in presence of better remission status (CR or VGPR) showed a significantly lower cumulative incidence of relapse (CIR) and a better EFS than those with PR (CIR 36,8% vs 87,0%, EFS 36,4% vs 9,4%) or persistent disease (CIR 99,5%, EFS 0%) ( Figures 2A , 3B ).…”

“…Patients with RMS, ES or NRSTS and primary bone metastasis or bone marrow involvement, with relapsed metastatic or primary refractory disease to standard treatment were eligible for haplo-HSCT. Patients have been in part already published in another context ( 28 , 29 ). Data analysis was done as of August 2022.…”

T Cells Directed against the Metastatic Driver Chondromodulin-1 in Ewing Sarcoma: Comparative Engineering with CRISPR/Cas9 vs. Retroviral Gene Transfer for Adoptive Transfer

“…High dose therapies with autologous hematopoietic stem-cell rescues have only been beneficial in selected subgroups [ 4 , 36 ]. Allogeneic hematopoietic stem-cell transplantation (allo-SCT) from healthy donors, as efficacious immunotherapy of leukemia, has offered hints for beneficial effects in solid tumors [ 37 ], possibly also in AES patients [ 4 , 36 , 38 ]. However, no difference in survival with reduced- versus high-intensity conditioning before allo-SCT [ 39 ] could be detected.…”

“…However, no difference in survival with reduced- versus high-intensity conditioning before allo-SCT [ 39 ] could be detected. There is also no difference in survival after HLA-mismatched versus HLA-matched allo-SCT [ 38 ]. These findings imply that allo-SCT is not sufficient for immunotherapy of AES, and novel therapeutic strategies are in urgent demand, such as TCR-based immunotherapy [ 40 ].…”

T‐cell replete haploidentical stem cell transplantation with low dose anti‐thymocyte globulin for relapsed/refractory Ewing sarcoma family tumors

“…Thiel et al 29 compared survival rates after hematopoietic allo SCT of HLA‐mismatched versus HLA‐matched advanced Ewing sarcoma patients and reported no significant difference. However, they performed ex vivo T‐cell depletion in haploidentical transplantation, which is different from our haploidentical SCT method.…”