Myeloablative Busulfan/Melphalan Consolidation Following Induction Chemotherapy For Patients With Newly Diagnosed High-Risk Neuroblastoma: Children'S Oncology Group Trial Anbl12p1

Consolidation using high-dose chemotherapy with autologous stem cell transplantation (ASCT) is an important component of frontline therapy for children with high-risk neuroblastoma. The optimal preparative regimen is uncertain, although recent data support a role for busulfan/melphalan (BuMel). The Children's Oncology Group (COG) conducted a trial (ANBL12P1) to assess the tolerability and feasibility of BuMel ASCT following a COG induction. Patients with newly diagnosed high-risk neuroblastoma who did not progress during induction therapy and met organ function requirements received i.v. busulfan (every 24 hours for 4 doses based on age and weight) and melphalan (140 mg/m(2) for 1 dose), followed by ASCT. Busulfan doses were adjusted to achieve to an average daily area under the curve (AUC) <5500 mu M x minute. The primary endpoint was the occurrence of severe sinusoidal obstruction syndrome (SOS) or grade >= 4 pulmonary complications within the first 28 days after completion of consolidation therapy. A total of 146 eligible patients were enrolled, of whom 101 underwent BuMel ASCT. The overall incidence of protocol-defined unacceptable toxicity during consolidation was 6.9% (7 of 101). Six patients (5.9%) developed SOS, with 4 (4%) meeting the criteria for severe SOS. An additional 3 patients (3%) experienced grade >= 4 pulmonary complications during consolidation. The median busulfan AUC was 4558 mu M x min (range, 3462 to 5189 x minute) for patients with SOS and 3512 mu M x min (2360 to 5455 mu M x minute) (P = .0142). No patients died during consolidation. From the time of study enrollment, the mean 3-year event-free survival for all 146 eligible patients was 55.6 +/- 4.2%, and the mean 3-year overall survival was 74.5 +/- 3.7%. The BuMel myeloablative regimen following COG induction was well tolerated, with acceptable pulmonary and hepatic toxicity. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.