Bone marrow involvement identifies a subgroup of advanced Ewing sarcoma patients with fatal outcome irrespective of therapy in contrast to curable patients with multiple bone metastases but unaffected marrow

Abstract

PurposeAdvanced Ewing sarcomas have poor prognosis. They are defined by early relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols.DesignOf 44 patients, 18 patients were enrolled into two subsequent MetaEICESS protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing sarcoma patients treated with EICESS 1992 between 1992 and 1996. MetaEICESS 1992 consisted of induction chemotherapy, whole body imaging directed radiotherapy to the primary tumor and metastases, tandem high-dose chemotherapy and autologous rescue. In MetaEICESS 2007 this treatment was complemented by allogeneic stem cell transplantation. EICESS 1992 comprised induction chemotherapy, local therapy to the primary tumor only followed by consolidation chemotherapy.ResultsIn MetaEICESS 8/18 patients survived in complete remission vs. 2/26 in EICESS 1992 (p<0.05). Survival did not differ between MetaEICESS 2007 and MetaEICESS 1992. Three MetaEICESS patients died of complications, all in MetaEICESS 1992. After exclusion of patients succumbing to treatment related complications (n=3), 7/10 patients survived without BM involvement, in contrast to 0/5 patients with BM involvement. This was confirmed in a multivariate analysis. There was no correlation between BM involvement and the number of metastases at diagnosis.ConclusionThe MetaEICESS protocols yield long-term disease-free survival in patients with advanced Ewing sarcoma. Allogeneic stem cell transplantation was not associated with increased death of complications. Bone marrow involvement is a risk factor distinct from multiple bone metastases.

Bone marrow biopsy in the initial staging of Ewing sarcoma: Experience from a single institution

“…The survival data observed in our series are in agreement with those reported in the literature, confirming the poor prognosis of patients with positive BMB.…”

MHC Class I-Restricted TCR-Transgenic CD4+ T Cells Against STEAP1 Mediate Local Tumor Control of Ewing Sarcoma In Vivo

“…Pediatric sarcoma, in particular Ewing sarcoma (EwS), are aggressive malignancies of enigmatic histogenesis [6] with a high metastatic capacity. Survival rates drastically decrease when patients present with multifocal disease or early relapse [7,8]. Standard treatment strategies for EwS include surgery, irradiation, and high-dose chemotherapy followed by autologous stem cell transplantation (SCT).…”

Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma

“…We re-evaluated data of eight patients (14–26 years) from previous publications with advanced ES and RMS, who received DLI after allo-SCT between 1997 and 2011 [ 3 , 9 ]. Median follow-up after allo-SCT was 27.5 months.…”

“…Patients with advanced Ewing sarcoma (ES), defined as ≥ 2 bone metastases, and/or bone marrow involvement or relapse ≤ 2 years after diagnosis have poor prognoses [ 1 ]. Intensified therapy regimens including high-dose chemotherapy (HDC), involved field irradiation, autologous and allogeneic stem cell transplantation (auto- and allo-SCT) [ 2 ] could improve survival in some of these patients, excluding patients with bone marrow (BM) infiltration who do not survive irrespective of therapy [ 3 ]. Advanced rhabdomyosarcoma (RMS) patients with metastatic disease at diagnosis or those with recurrent disease have 5-year-survival rates not exceeding 30% [ 4 ].…”