Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients with Newly Diagnosed High-Risk Neuroblastoma: Children's Oncology Group (COG) trial ANBL12P1

Abstract PURPOSE 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, though 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 AND METHODS Patients with newly diagnosed, high-risk neuroblastoma who did not progress during induction therapy and met organ function requirements received intravenous busulfan [every 24 hours x 4 doses based on age and weight] and melphalan (140 mg/m2 x 1 dose) followed by ASCT. Busulfan doses were adjusted to achieve to an average daily area under the curve (AUC) RESULTS 146 eligible patients enrolled; 101 underwent BuMel ASCT. The overall incidence of protocol-defined unacceptable toxicity during consolidation was 6.9% (7/101). A total of six (5.9%) patients developed SOS, with four (4%) patients meeting criteria for severe SOS. An additional three (3%) patients experienced Grade ≥4 pulmonary complications during consolidation. The median busulfan AUCs for patients with and without SOS were 4,558 µM × min (range 3,462-5,189) and 3,512 µM × min (2,360–5,455), respectively (p=0.0142). No patients died during consolidation. From time of study enrollment, the 3-year event-free survival for all 146 eligible patients was 55.6±4.2% and 3-year overall survival was 74.5±3.7%. CONCLUSION A BuMel myeloablative regimen following COG induction was well tolerated, with acceptable pulmonary and hepatic toxicity.