title: Thiotepa and melphalan based single, tandem, and triple high dose therapy and autologous stem cell transplantation for high risk neuroblastoma.
abstract: BACKGROUND
  Outcome of high risk neuroblastoma (NBL) remains unsatisfactory in spite of intensive treatment efforts. Consolidation with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) has been intensified with tandem and triple cycles with promising results. Our purpose was to improve the outcome with two or three HD-consolidations.
  
  
  METHODS
  Thirty six children with high risk NBL, diagnosed 1995-2010, had intensive induction and surgery, and were stratified to single, tandem or triple HD-therapy and ASCT, followed by local irradiation and cis-retinoic acid. In inoperable patients surgery was facilitated by preoperative HD-melphalan. Long-term outcome of our old cohort from 1987-1994 was updated.
  
  
  RESULTS
  Ten year event-free survival (EFS) from diagnosis was 0.44+/-0.10 of the old and 0.43+/-0.085 of the new cohort. EFS from the last ASCT was 0.53 +/-0.12 and 0.48+/-0.091, respectively. Preoperative HD-melphalan rendered 73% of bulky primaries operable in the new cohort. The 5-yr EFS from ASCT was 0.46+/-0.15 for single and 0.73+/-0.15 for tandem ASCT (P = 0.19). All triple ASCT patients, selected by poor/slow response, relapsed or died.
  
  
  CONCLUSIONS
  Thiotepa- and melphalan based HD regimens, with or without total body irradiation (TBI), appeared to give an outcome comparable to major NBL study groups with acceptable toxicity. Tandem HD therapy gave a 5-year EFS of 73%, whereas a third HD consolidation did not offer any additional advantage for ultra high risk patients with slow response. Pediatr Blood Cancer 2012; 59: 1190-1197. © 2012 Wiley Periodicals, Inc.
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. ulla.pihkala@hus.fi
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
authors.forename: Liisa
authors.initials: L
authors.lastname: Hovi
authors.forename: Antti
authors.initials: A
authors.lastname: Koivusalo
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jahnukainen
authors.forename: Riitta
authors.initials: R
authors.lastname: Karikoski
authors.forename: Hannu
authors.initials: H
authors.lastname: Sariola
authors.forename: Sakari
authors.initials: S
authors.lastname: Wikström
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D009447:Neuroblastoma / Q000401:mortality / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D012074:Remission Induction; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage* / Q000009:adverse effects; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
chemical_list: D013852:Thiotepa; D008558:Melphalan