High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors

Abstract

The purpose of the study was to evaluate the feasibility and safety of two cycles of high-dose chemotherapy (HDT) followed by autologous hematopoietic SCT (HSCT) in patients with poor prognosis Ewing family of tumors (EFT). Twenty patients with primary metastatic bulky disease or recurrent EFT were enrolled to a treatment protocol with two cycles of HDT and HSCT. Patients tolerated well the first (n ¼ 20) and second (n ¼ 13) cycles, with limited and predictable toxicities. Only one (5%) TRM occurred during the second cycle. Myeloid engraftment occurred at the median of 11 days after both cycles. At 3 years, the overall and EFS were 45% (confidence interval; CI 0.22, 0.69) and 47% (CI 0.25, 0.70), respectively, for the entire group and 58% (CI 0.30, 0.86) for patients who completed two cycles. Dose intensification with two cycles of HDT and HSCT is feasible and safe, with low and acceptable treatmentrelated morbidity and mortality. Adding a second course of therapy does not impair engraftment. However, only 65% of the patients were able to proceed to the second cycle. Further studies are required to define the optimal mode of delivery of HDT and HSCT in treatment of advanced EFT.

Tandem high-dose chemotherapy strategy as first-line treatment of primary disseminated multifocal Ewing sarcomas in children, adolescents and young adults

“…Although the comparison is historical, the populations were similar in terms of the EE99-R3 risk score (median = 4 (2.5-5) and 3 (0-6) for the tandem-HDC and single-HDC strategy, respectively) and the percentage of patients who actually received Mel/Bu (72% versus 60% for the tandem-HDC and the single-HDC strategy, respectively; P = 0.3). 6 Results of our series were also comparable to previously published studies of tandem-HDC strategies with other alkylating agents and platinum derivatives in primary advanced or relapsed ES, although comparison is rendered difficult by the heterogeneity of the population in the different published series [9][10][11][12] (Table 3). Our study presents the largest homogeneous cohort of PDMES treated with the same tandem-HDC programme, and with a long median follow-up.…”

“…31 Table 3. Comparison of populations and survival rates with the EE99-R3 arm and other tandem-HDC strategies in the treatment of ES Our study Ladenstein et al 6 Burdach et al 9 Burke et al 11 Rosenthal et al 10 Lashkari et al 12 No PME at the start Tandem HDC in metastatic Ewing sarcoma S Loschi et al…”

“…8 In multimetastatic ES, the results of nonrandomised studies evaluating different tandem-HDC regimens remain controversial. [9][10][11][12] Our aim was to determine the feasibility, safety and efficacy of a tandem-HDC programme with high-dose (HD) thiotepa followed by melphalan-busulfan (Mel/Bu).…”

Specificities of Autologous Haematopoietic Stem Cell Transplantation in Children: A Single Centre Experience

“…High-dose chemotherapy in Ewing's sarcoma consists mostly of melphalan and bulsulfan. Utilising AHSCT in the treatment of these patients accomplishes equal or higher survival rates with 3-5 year disease-free survival in 20-65% of patients [10][11][12][13][14][15]. Our experiences confirm that high-risk Ewing's sarcoma/ PNET patients certainly belong to the group that can greatly benefit from stem cell transplant.…”

Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing’s sarcoma

“…Two studies, by Rosenthal et al 11 and Hawkins et al, 12 describe the attempts to perform two subsequent HDTs in poor prognosis or relapsed patients; 3-year survival in those patients, 38% and 45%, seems to be promising.…”