Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma (original) (raw)
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Korean journal of pediatrics, 2013
We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 mon...
Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors
Bone Marrow Transplantation, 2006
The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P ¼ 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.
Frontiers in Oncology, 2023
Background: Prognosis of children with primary disseminated or metastatic relapsed sarcomas remains dismal despite intensification of conventional therapies including high-dose chemotherapy. Since haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of hematological malignancies by mediating a graft versus leukemia effect, we evaluated this approach in pediatric sarcomas as well. Methods: Patients with bone Ewing sarcoma or soft tissue sarcoma who received haplo-HSCT as part of clinical trials using CD3+ or TCRa/b+ and CD19+ depletion respectively were evaluated regarding feasibility of treatment and survival. Results: We identified 15 patients with primary disseminated disease and 14 with metastatic relapse who were transplanted from a haploidentical donor to improve prognosis. Three-year event-free survival (EFS) was 18,1% and predominantly determined by disease relapse. Survival depended on response to pre-transplant therapy (3y-EFS of patients in complete or very good partial response: 36,4%). However, no patient with metastatic relapse could be rescued. Conclusion: Haplo-HSCT for consolidation after conventional therapy seems to be of interest for some, but not for the majority of patients with high-risk pediatric sarcomas. Evaluation of its future use as basis for subsequent humoral or cellular immunotherapies is necessary.
Bone Marrow Transplantation, 2021
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).
Bone Marrow Transplantation, 2012
According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing 0 s sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m 2 i.v. on day À 2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P ¼ 0.008); OS 0.31 vs 0.71 (P ¼ 0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P ¼ 0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features.
Annals of Oncology, 2011
transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. Results: Median overall survival was 7.9 months [61.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (61.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). Conclusions: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.
Biology of Blood and Marrow Transplantation, 2013
Children with relapsed or refractory solid tumors face dismal prognoses, and novel therapies are desperately needed. Allogeneic hematopoietic cell transplantation (HCT) offers potential for cell-based therapy, but the toxicity of myeloablation limits this approach in heavily pretreated patients. We sought to determine the feasibility of HCT in a cohort of 24 children with incurable solid tumors using human leukocyte antigene matched sibling or unrelated donors and a minimal conditioning regimen. Before stem cell infusion, all patients received 3 daily doses of 30 mg/m 2 fludarabine followed by 2 Gy of total body irradiation. Hematopoietic cell recovery was rapid and reliable. Median time to neutrophil engraftment was 13.5 days for sibling donors and 12 days for unrelated donors. Donor lymphocyte infusions were used safely in 4 patients, all of whom had either improved chimerism or apparent tumor response. Graft-versus-host disease was comparable across donor sources and did not affect survival. Relapse remains a substantial barrier, although objective graft-versus-tumor effect was observed in several patients. Four patients with detectable disease before HCT achieved a complete response for at least 30 days after HCT, and two remain long-term survivors. Three patients were in complete response before HCT and remained in remission for 3, 6, and 74 months after HCT. Early disease response was associated with improved survival. Allogeneic HCT using this conditioning regimen offers a potential platform for novel immunotherapies.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018
Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis ≥ 200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year event-free survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122)....
Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma
Bone Marrow Transplantation, 2008
The aim of this study was to identify risk factors associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116 patients underwent ASCT in 1989-2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score o90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of PFS in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30-69) and 34% (95% CI 22-47) respectively. The 5-year probability of PFS in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3-30). PFS rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials.