title: Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas.
abstract: The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m(2) intravenously (i.v.) Day 1, ifosfamide 2 g/m(2) i.v. Days 3- 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m(2) i.v. Days 1-2, thiotepa 40 mg/m(2) i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m(2) i.v. Day -5, thiotepa 2×5 mg/kg i.v. Days -4 to -3 and etoposide 150 mg/m(2) i.v. Days -5 to -3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173).
authors.affiliation: Department of Hematology and Oncology, Charite Universitätsmedizin Berlin, Germany. agnieszka.korfel@charite.de
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korfel
authors.forename: Thomas
authors.initials: T
authors.lastname: Elter
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Matthias
authors.initials: M
authors.lastname: Hänel
authors.forename: Robert
authors.initials: R
authors.lastname: Möhle
authors.forename: Roland
authors.initials: R
authors.lastname: Schroers
authors.forename: Marcel
authors.initials: M
authors.lastname: Reiser
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Jan
authors.initials: J
authors.lastname: Eucker
authors.forename: Christian
authors.initials: C
authors.lastname: Scholz
authors.forename: Bernd
authors.initials: B
authors.lastname: Metzner
authors.forename: Alexander
authors.initials: A
authors.lastname: Röth
authors.forename: Josef
authors.initials: J
authors.lastname: Birkmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlegel
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Gerard
authors.initials: G
authors.lastname: Illerhaus
authors.forename: Lars
authors.initials: L
authors.lastname: Fischer
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D060186:Infusions, Spinal; D008223:Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents