title: Toxicities of busulfan/melphalan versus carboplatin/etoposide/melphalan for high-dose chemotherapy with stem cell rescue for high-risk neuroblastoma.
abstract: The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ(2) or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Desai
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Heneghan
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Bunin
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Grupp
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bagatell
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Seif
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D002066:Busulfan / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D007223:Infant; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D052016:Mucositis / Q000139:chemically induced; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000633:toxicity*; D009447:Neuroblastoma / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D010198:Pancytopenia / Q000139:chemically induced; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D005047:Etoposide; D016190:Carboplatin; D002066:Busulfan; D008558:Melphalan