title: Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma.
abstract: BACKGROUND
  Outcomes for high-risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long-term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing.
  
  
  METHODS
  We retrospectively reviewed data from 87 patients with high-risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n = 12) and Chicago Pilot 2 (CP2; n = 75).
  
  
  RESULTS
  The 15-year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1-45.0%). The 10- and 15-year cumulative incidence of SMN was 16.5% (95%CI, 7.2-38.0%) and 34.2% (95%CI, 18.6-63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n = 2 in CP1 and n = 8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma.
  
  
  CONCLUSIONS
  A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life-long follow-up of survivors who were treated using modern therapy.
authors.affiliation: Division of Hematology/Oncology/Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Illinois.
authors.forename: Alissa
authors.initials: A
authors.lastname: Martin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schneiderman
authors.forename: Irene B
authors.initials: IB
authors.lastname: Helenowski
authors.forename: Elaine
authors.initials: E
authors.lastname: Morgan
authors.forename: Kimberley
authors.initials: K
authors.lastname: Dilley
authors.forename: Karina
authors.initials: K
authors.lastname: Danner-Koptik
authors.forename: Mohamad
authors.initials: M
authors.lastname: Hatahet
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Morris
authors.initials: M
authors.lastname: Kletzel
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hijiya
mesh_terms: D000293:Adolescent; D064592:Autografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D016609:Neoplasms, Second Primary / Q000401:mortality / Q000628:therapy; D009447:Neuroblastoma / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate
keywords: AML; MDS; alkylating agents; epipodophyllotoxins; neuroblastoma; second malignant neoplasm