Feasibility of a tandem autologous peripheral blood stem cell transplant regimen for high risk neuroblastoma in a cooperative group setting: A Pediatric Oncology Group study: A Report from the Children's Oncology Group

Abstract

Background The Pediatric Oncology Group performed a pilot study to assess the feasibility of tandem high dose chemotherapy with stem cell rescue (HDC/SCR). We report here the results of this single arm trial of induction chemotherapy, local control measures (surgery and local radiation), and tandem HDC/SCR. Procedure Patients with high risk neuroblastoma underwent five cycles of induction chemotherapy and resection of primary tumors. PBSC were collected after Course 3 without exvivo manipulation. Myeloablative chemotherapy was performed in rapid sequence after induction chemotherapy and surgery. The ability of patients to complete both cycles of HDC/SCR was a primary endpoint. Transplant-related toxicity, progression-free survival (PFS) and overall survival (OS) were recorded. Results A total of 33 patients were enrolled. Twenty-two patients completed at least one HDC/SCR procedure and 17 patients completed both. Only one patient had insufficient stem cells collected for both transplants. There was one transplant-related death; engraftment was rapid and toxicity was as expected. The PFS of the 33 patients treated on this study is 24.2%±7.5% and OS is 36.4%±8.4% at 5 years. For patients who received at least one transplant PFS is 36.4%±11.0% and OS is 45.5%±11.2% at 5 years. Conclusions The treatment of high risk neuroblastoma with tandem HDC/SCR is feasible in terms of transplant-related mortality and the ability to collect adequate PBSC for 2 transplants. The outcomes from this intensified treatment have been used to design a Children's Oncology Group Phase III study testing the efficacy of tandem HDC/SCR.

A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children’s Oncology Group study ANBL00P1

“…Most patients (80%) went on to receive HDC/SCR, and 79% of patients who underwent a first HDC/SCR went on to receive a second transplant, comparable to previous trials.(ref. 10, 13) With the exception of one patient who required an additional stem cell rescue using the backup PBSCs following the first HDC/SCR, stem cell collection was not a limiting factor for proceeding to HDC/SCR, consistent with the feasibility of collecting stem cells from chemotherapy-treated patients in prior studies.(ref. 10, 24) Toxicities were as expected for the planned intensity of therapy, and TRM was below the predetermined safety threshold.…”

“…20, 21, 22) In addition to its feasibility and safety in a previous study [Pediatric Oncology Group (POG) 9640],(ref. 13) thiotepa has good central nervous system (CNS) penetration, which may be important given recent data suggesting an increased risk of CNS recurrence in some neuroblastoma patients.(ref. 23); however, the present study was neither powered nor designed to measure CNS-specific relapse rates, especially as head CTs were not in routine use for recurrence surveillance or staging at that time.…”

“…The present study confirms the feasibility findings of Granger, et al, (ref. 13) and adds important data regarding the decreased safety of CD34 selection in this patient population; whereas, the POG trial used only unmanipulated peripheral stem cells. In addition, from a therapeutic development standpoint, while both studies demonstrated feasibility of tandem transplantation in children with high-risk neuroblastoma, the present manuscript demonstrates the feasibility of the exact HDC/SCR regimens subsequently used as the experimental arm of COG ANBL0532.…”

“…4) This regimen was selected as the first HDC/SCR cycle because it was expected to have less toxicity than CEM based on POG 9640.(ref. 13) 2) CEM was selected as the second regimen in order to facilitate the most straightforward evaluation of consolidation regimens in a subsequent single vs. tandem transplant cooperative group trial.…”

Tandem high-dose chemotherapy with thiotepa and busulfan–melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients

“…[30][31][32][33][34] A phase III study comparing two different consolidation strategies (CEM vs CEM followed by HD thiotepa-cyclophosphamide) with ASCT in HR-NBL patients has been ruled out by the COG [NCT00567567].…”