title: Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin.
abstract: Since 2003, high-risk neuroblastoma (HR-NB) patients at our center received anti-GD2 antibody 3F8/GM-CSF + isotretinoin - but not myeloablative therapy with autologous stem-cell transplantation (ASCT). Post-ASCT patients referred from elsewhere also received 3F8/GM-CSF + isotretinoin. We therefore accrued a study population of two groups treated during the same period and whose consolidative therapy, aside from ASCT, was identical. We analyzed patients enrolled in 1st complete/very good partial remission (CR/VGPR). Their event-free survival (EFS) and overall survival (OS) were calculated from study entry. Large study size allowed robust statistical analyses of key prognosticators including MYCN amplification, minimal residual disease (MRD), FCGR2A polymorphisms, and killer immunoglobulin-like receptor genotypes of natural killer cells. The 170 study patients included 60 enrolled following ASCT and 110 following conventional chemotherapy. The two cohorts had similar clinical and biological features. Five-year rates for ASCT and non-ASCT patients were, respectively: EFS 65% vs. 51% (p = .128), and OS 76% vs. 75% (p = .975). In multivariate analysis, ASCT was not prognostic and only MRD-negativity after two cycles of 3F8/GM-CSF correlated with significantly improved EFS and OS. Although a trend towards better EFS is seen with ASCT, OS is near identical. Cure rates may be similar, as close surveillance detects localized relapse and effective salvage treatments are applied. ASCT may not be needed to improve outcome when anti-GD2 immunotherapy is used for consolidation after dose-intensive conventional chemotherapy.
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Kushner
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Ostrovnaya
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Irene Y
authors.initials: IY
authors.lastname: Cheung
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuk
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Kramer
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Roberts
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Basu
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Karima
authors.initials: K
authors.lastname: Yataghene
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Nai-Kong V
authors.initials: NK
authors.lastname: Cheung
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003879:Dermatologic Agents / Q000627:therapeutic use; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy / Q000401:mortality*; D007223:Infant; D007231:Infant, Newborn; D015474:Isotretinoin / Q000627:therapeutic use*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000401:mortality*; D015996:Survival Rate; D014182:Transplantation, Autologous
chemical_list: D000911:Antibodies, Monoclonal; D003879:Dermatologic Agents; D005732:Gangliosides; C019403:ganglioside, GD2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015474:Isotretinoin
keywords: anti-GD2 antibody; autologous stem-cell transplantation; immunotherapy; minimal residual disease; pediatric oncology