title: High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors: A Report From the Children's Oncology Group (CCG-99702).
abstract: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS).
  
  
  
  The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR.
  
  
  
  The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m(2) /day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m(2) /day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%.
  
  
  
  The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon.
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Nazemi
authors.affiliation: Children's Hospital of Orange County, Cancer Institute, Orange, California.
authors.forename: Violet
authors.initials: V
authors.lastname: Shen
authors.affiliation: Children's Hospital of Los Angeles, Neuro-Oncology Program, Los Angeles, California.|Division of Hematology, Oncology and BMT, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
authors.affiliation: Department of Biostatistics, Saint Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: James
authors.initials: J
authors.lastname: Boyett
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.affiliation: Department of Hematology-Oncology, Children's National Health System, Washington, District of Columbia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lafond
authors.affiliation: Hassenfeld Children's Center, Langone Medical Center, New York University, New York, New York.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Gardner
authors.affiliation: Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Washington, District of Columbia.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon.|Department of Child Health, University of Arizona and Phoenix Children's Hospital, Phoenix, Arizona.
authors.forename: H Stacy
authors.initials: HS
authors.lastname: Nicholson
mesh_terms: D000293:Adolescent; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D061888:Craniospinal Irradiation / Q000009:adverse effects; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D060828:Induction Chemotherapy / Q000009:adverse effects; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000401:mortality / Q000628:therapy*
keywords: CCG-99702; high-risk medulloblastoma (MB); myeloablative chemotherapy; primitive neuroectodermal tumor (PNET); sinusoidal obstructive syndrome (SOS); veno-occlusive disease (VOD)