Myeloablative Busulfan/Melphalan Consolidation following Induction Chemotherapy for Patients with Newly Diagnosed High-Risk Neuroblastoma: Children’s Oncology Group Trial ANBL12P1

Granger MM, Naranjo A, Bagatell R, DuBois SG, McCune JS, Tenney SC, Weiss BD, Mosse YP, Asgharzadeh S, Grupp SA, Hogarty MD, Gastier-Foster JM, Mills D, Shulkin BL, Parisi MT, London WB, Han-Chang J, Panoff J, von Allmen D, Jarzembowski JA, Park JR, Yanik GA. Myeloablative Busulfan/Melphalan Consolidation following Induction Chemotherapy for Patients with Newly Diagnosed High-Risk Neuroblastoma: Children’s Oncology Group Trial ANBL12P1. Transplant Cell Ther. 2021 Jun;27(6):490.e1-490.e8. doi: 10.1016/j.jtct.2021.03.006. Epub 2021 Mar 6. PubMed PMID: 33823167; PubMed Central PMCID: PMC8855886.

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 with newly diagnosed, high-risk neuroblastoma who did not progress during induction therapy and met organ function requirements received intravenous busulfan [every 24 hours × 4 doses based on age and weight] and melphalan (140 mg/m2 × 1 dose) followed by ASCT. Busulfan doses were adjusted to achieve to an average daily area under the curve (AUC) <5,500 μM×min. The primary endpoint was the occurrence of severe sinusoidal obstruction syndrome (SOS) or Grade ≥4 pulmonary complications within the first 28 days of completion of consolidation therapy.