title: Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs).
  
  
  METHODS
  Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR.
  
  
  RESULTS
  Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC.
  
  
  CONCLUSIONS
  Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. modaks@mskcc.org
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.forename: Sharon
authors.initials: S
authors.lastname: Gardner
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Dunkel
authors.forename: Casilda
authors.initials: C
authors.lastname: Balmaceda
authors.forename: Marc K
authors.initials: MK
authors.lastname: Rosenblum
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
authors.forename: Steven
authors.initials: S
authors.lastname: Halpern
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018237:Germinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008499:Medical Records; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009518:New York; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D013852:Thiotepa