The Efficacy of High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Ewing Sarcoma Patients

Background: The role of high-dose chemotherapy followed by autologous stem-cell transplantation (HDCT–ASCT) in advanced Ewing sarcoma remains uncertain, with mixed prospective data and heterogeneous retrospective findings. Materials and Methods: We performed a single-center, retrospective cohort study of consecutive patients with histologically confirmed ES who received HDCT–ASCT after ≥1 prior systemic therapy line (N=46). Conditioning was ICE. Prespecified endpoints were overall survival (OS; diagnosis→death), post-transplant overall survival OS-2 (ASCT→death), and progression-free survival PFS (ASCT→progression/death). Survival was estimated by Kaplan–Meier and compared by log-rank. Prognostic factors (age at diagnosis, primary tumor site, metastatic organ involvement) were evaluated using Cox models. Results: Median age at diagnosis was 23.5 years (14–55); 69.6% were male and 21.7% had metastatic disease at presentation. Median OS was 42.0 months, median PFS and OS-2 after HDCT–ASCT were 5.0 months and 8.0 months, respectively. Younger age (≤23 years) was associated with longer OS (50.0 vs 34.0 months; p=0.027). Primary tumor site was not independently associated with PFS, OS-2, or OS. Metastatic site showed endpoint-specific effects: liver metastasis independently predicted worse OS (HR 5.411; p=0.006), while lung metastasis was associated with shorter PFS (HR 6.037; p=0.016) and OS-2 (HR 2.672; p=0.025). Post-transplant best responses were CR 8.7%, PR 17.4%, SD 15.2%, and PD 58.7%. Grade 3–4 hematologic toxicities were universal (febrile neutropenia, neutropenia, thrombocytopenia 100%; anemia 86.9%); common non-hematologic events included nausea/vomiting (82.6%), diarrhea (78.2%), and mucositis/stomatitis (65.2%). Treatment-related mortality was 2.1% (1/46). Conclusions: In this young-adult–predominant cohort, HDCT–ASCT achieved limited disease control with substantial but manageable toxicity. Prognosis was driven more by age and metastatic organ involvement than by primary site, with liver metastasis portending inferior OS and lung metastasis adversely affecting PFS/OS-2. These data support risk-adapted patient selection and exploration of post-transplant maintenance strategies in future prospective studies.