High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis

Purpose: To determine whether consolidation therapy with high-dose melphala n, etoposide, and total-body irradiation (TBI) with autologous stem-cell su pport would improve the prognosis for patients with newly diagnosed metasta tic Ewing's sarcoma (ES). Patients and Methods: Thirty-two eligible patients with newly diagnosed ES metastatic to bone and/or bone marrow were enrolled onto this study. Treatm ent was initially comprised of five cycles of induction chemotherapy (cyclo phosphamide, doxorubicin, and vincristine alternating with ifosfamide and e toposide) and local control, Peripheral-blood stem-cell collection was perf ormed after the second cycle of chemotherapy, with delay if the bone marrow was persistently involved. If patients had a good response to initial ther apy, they proceeded to consolidation therapy with melphalan, etoposide, TBI , and stem-cell support, Results: Of the 32 eligible patients, 23 proceeded to high-dose therapy con solidation. Of the nine patients who did not proceed to consolidation, four were secondary to progressive disease and two were secondary to toxicity. Three patients died from toxicity during the high-dose phase of the therapy , the majority of the patients who underwent high-dose consolidation therap y experienced relapse and died with progressive disease. Two-year event-fre e survival (EFS) for all eligible patients is 20%. The 2-year post-stem-cel l reconstitution EFS for the subset of 23 patients who received consolidati on therapy is 24%. Analysis of peripheral-blood stem-cell collections by mo lecular techniques for minimal residual disease showed contamination of at least some samples by tumor cells in all three patients with available data . Conclusion: Consolidation with high-dose melphalan, etoposide, TBI, and aut ologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.