title: Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases.
abstract: BACKGROUND
  Relapsing primary central nervous system lymphoma carries a poor prognosis when treated with conventional chemotherapy with a one-year overall survival of 25-40%. Encouraging results have been shown with intensive chemotherapy followed by autologous hematopoietic stem cell rescue. We report the results of a large multicenter retrospective analysis of intensive chemotherapy followed by hematopoietic stem cell rescue in immunocompetent adult patients with primary central nervous system lymphoma or intraocular lymphoma after the failure of high-dose methotrexate-based treatment.
  
  
  METHODS
  Patients were included if they received intensive chemotherapy with a combination of thiotepa, busulfan and cyclophosphamide. Seventy-nine patients (median age 52.4 years, range 23-67 years) were identified. All of the patients except 5 received a salvage treatment after the failure of high-dose methotrexate. After salvage treatment and just before intensive chemotherapy followed by hematopoietic stem cell rescue, 32 patients were in complete response, 26 patients were in partial response, 2 patients had stable disease and 19 patients had progressive disease.
  
  
  RESULTS
  With a median follow up of 56 months, the 5-year overall survival probability was 51% in the whole population and 62% among patients who were chemosensitive to the salvage treatment. The 5-year event-free survival probability was 37.8% in the whole population and 43.7% in the chemosensitive subpopulation. Neurocognitive assessments in a subset of patients suggest no evidence of intensive chemotherapy-induced neurocognitive decline.
  
  
  CONCLUSIONS
  Thiotepa, busulfan and cyclophosphamide-based intensive chemotherapy is an effective treatment for refractory and recurrent primary central nervous system lymphoma in chemosensitive patients up to 65 years of age. The role of intensive chemotherapy followed by hematopoietic stem cell rescue in chemorefractory patients needs to be more accurately defined.
authors.affiliation: Department of Hematology, Hôpital René Huguenin, Institut Curie, Saint-Cloud, France. carole.soussain@curie.net
authors.forename: Carole
authors.initials: C
authors.lastname: Soussain
authors.forename: Sylvain
authors.initials: S
authors.lastname: Choquet
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fourme
authors.forename: Daniel
authors.initials: D
authors.lastname: Delgadillo
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.forename: Hervé
authors.initials: H
authors.lastname: Ghesquières
authors.forename: Gandhi
authors.initials: G
authors.lastname: Damaj
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dupriez
authors.forename: Jacques
authors.initials: J
authors.lastname: Vargaftig
authors.forename: Alberto
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Caroline
authors.initials: C
authors.lastname: Houillier
authors.forename: Luc
authors.initials: L
authors.lastname: Taillandier
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblond
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005134:Eye Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan