High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma

Abstract

Summary:Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. Keywords: Wilms tumor; high-dose chemotherapy; autologous bone marrow transplantation A child with newly diagnosed Wilms tumor (WT) has a probability of about 85% of being cured with multimodal treatment nowadays. Current treatment strategies stratify intensity and scheduling of the different treatment modalities -surgery, radiation and chemotherapy -according to biologic and prognostic features of the initial disease, most importantly, stage and histology. Three large multiinstitutional study groups have contributed to this development: the National Wilms Tumor Study (NWTS), USA, 1-3 the United Kingdom Children's Cancer Study Group 4,5 and the International Society of Pediatric Oncology (SIOP). [6][7][8][9] For the 15% of patients with relapse or refractory disease, attempts have been made to use a similar risk-adapted strategy. These efforts were based upon the analysis of Grundy et al 10 demonstrating a 3-year survival of 30% in 367 patients who relapsed following treatment within studies NWTS-2 and -3. The authors identified prognostic factors with respect to time and site of relapse, histology and previous therapy, and used them to identify a good-risk group of relapsed patients who had a survival of >40% with conventional therapy. 10 For the complementary group of very high-risk patients, treatment alternatives were investigated. In phase II studies, single drugs or combinations gave the following results: single drug etoposide: 42% of response; 11 ifosfamide plus etoposide: overall response rate 39.5%; 12 etoposide and ifosfamide: 15% complete and 54% partial remission; 13 etoposide plus carboplatin: 70% response. 14 None of these approaches, however, could improve the long-term survival of these patients above 30%. 14 Consequently, dose-response strategies were investigated. Warkentin et al 15 who administered etoposide and thiotepa, reported eight out of 12 relapse-free survivors after 1 year. The Solid Tumor Registry of the EBMT reviewed 24

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…Currently, the SIOP-RTSG board suggests a regimen based on unpublished but presented data from the COG 27 , including combinations of vincristine, irinotecan, cyclophosphamide, carboplatin, etoposide, and doxorubicin, followed by high-dose chemotherapy and autologous stem cell transplantation at the discretion of the treating physician. The role of upfront high-dose chemotherapy for this subgroup is under debate, but a trend towards favourable outcomes has been reported by several groups in the primary and relapsed settings [28][29][30] . Details of this suggested regimen were added as an appendix to the UMBRELLA protocol.…”

Value and difficulties of a common European strategy for recurrent Wilms’ tumor

“…Trials with high-dose chemotherapy and ASCR obtained a better outcome than historical controls, with 3 or 4-year OS rates ranging from 60 to 73% [9][10][11]14,15].…”

“…The introduction of these drugs into intensive chemotherapy regimens or high-dose therapy with autologous stem-cell rescue (ASCR) led to DFS rates ranging between 50 and 70% for children with recurrent WT [9][10][11][12][13][14][15].…”

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

“…Malignant tumours that require AHSCT treatment are considered rare. These can be lymphomas or solid tumours such as neuroblastomas, Ewing's sarcomas/primitive neuroectodermal tumours (PNET), rhabdomyosarcomas, nephroblastomas, brain tumours and germ-cell tumours [1][2][3][4].…”