title: High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma.
abstract: BACKGROUND
  Stage 4b retinoblastoma (central nervous system metastatic disease) has been lethal in virtually all cases reported. Here we describe a series of eight patients treated with intensive chemotherapy, defined as the intention to include high-dose chemotherapy with autologous hematopoietic stem cell rescue.
  
  
  METHODS
  Induction chemotherapy included cyclophosphamide and/or carboplatin with a topoisomerase inhibitor. High-dose chemotherapy regimens were carboplatin and thiotepa with or without etoposide (n = 3) or carboplatin, etoposide, and cyclophosphamide (n = 2).
  
  
  RESULTS
  Seven patients had leptomeningeal disease and one patient had only direct extension to the CNS via the optic nerve. Three patients had stage 4b disease at the time of original diagnosis of the intra-ocular retinoblastoma; five had later onset at a median of 12 months (range 3-69 months). One patient died of toxicity (septicemia and multi-organ system failure) during induction and two had disease progression prior to high-dose chemotherapy. Five patients received high-dose chemotherapy at a median of 6 months (range 4-6) post-diagnosis of stage 4b disease. Two patients survive event-free at 40 and 101 months; one was irradiated following recovery from the high-dose chemotherapy.
  
  
  CONCLUSIONS
  Intensive multimodality therapy may be beneficial for some patients with stage 4b retinoblastoma. Longer follow-up will determine whether it has been curative.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. dunkeli@mskcc.org
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Dunkel
authors.forename: Helen S L
authors.initials: HS
authors.lastname: Chan
authors.forename: Rima
authors.initials: R
authors.lastname: Jubran
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Chantada
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Khakoo
authors.forename: David H
authors.initials: DH
authors.lastname: Abramson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D019572:Retinal Neoplasms / Q000175:diagnosis / Q000628:therapy*; D012175:Retinoblastoma / Q000175:diagnosis / Q000628:therapy*; D014182:Transplantation, Autologous