High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of Pediatric Oncology study.

Abstract

The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy define children with very-poor-risk recurrent WT. Despite high treatment-related toxicity, about half of these patients remain disease-free at 3 years. Patient outcome is statistically better when high-dose chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol

“…Furthermore, treatment with high-dose chemotherapy (extremely high, potentially toxic doses of chemo therapy) followed by autologous stem cell transplantation (HD-ASCT) to consolidate the second complete remission seems to be of value 21,55 . In total, the outcomes of 24 patients with CCSK who experienced relapse and received HD-ASCT have been reported in the literature, of whom 50% were alive without disease after a median follow-up duration of 52 months, whereas the average 5-year OS of patients with relapsed CCSK is about 26% 21,[55][56][57][58] . Importantly, this HD-ASCT treatment was mostly given to a selected group of patients with relapsed disease who already achieved second complete remission; thus, the positive effect of HD-ASCT might (in part) be attributable to this selection of patients.…”

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

“…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].…”

“…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].…”

Autologous stem cell transplantation for high-risk pediatric solid tumors

“…Previous reports have documented a 3-20% incidence of transplant-related mortality following autotransplantation for pediatric solid tumors. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] The first regimen that we evaluated, protocol MT 8911, consisting of etoposide, thiotepa and cyclophosphamide was associated with one patient experiencing peri-transplant mortality. The second regimen that we evaluated, MT 9408, consisted exclusively of alkylating drugs (busulfan, melphalan and thiotepa) and was associated with two toxic deaths, both from complications of hepatic veno-occlusive disease.…”

“…[1][2][3] ASCT is under evaluation as consolidation therapy for patients with metastatic disease and for those who have relapsed after intensive therapies. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Durable responses have been reported for neuroblastoma, 10,13,14,16 Ewing's sarcoma, 5,9,[15][16][17] rhabdomyosarcoma, 8,15,17 Wilms tumor 15,18 and brain tumors. [19][20][21][22][23][24][25][26] We present our experience with two consecutive studies evaluating the role of myeloablative chemotherapy followed by ASCT for young patients with aggressive solid tumors.…”