title: Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.
abstract: BACKGROUND
  The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL.
  
  
  METHODS
  Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide.
  
  
  RESULTS
  No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse.
  
  
  CONCLUSIONS
  Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.
authors.affiliation: Division of Hematology/Oncology, Hematopoietic Stem Cell Transplant Program and Lymphoma Program, Feinberg School of Medicine, Northwestern University, 676 North St. Clair, Chicago, IL 60611, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Evens
authors.forename: J K
authors.initials: JK
authors.lastname: Altman
authors.forename: B B
authors.initials: BB
authors.lastname: Mittal
authors.forename: N
authors.initials: N
authors.lastname: Hou
authors.forename: A
authors.initials: A
authors.lastname: Rademaker
authors.forename: D
authors.initials: D
authors.lastname: Patton
authors.forename: L
authors.initials: L
authors.lastname: Kaminer
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: S
authors.initials: S
authors.lastname: Duffey
authors.forename: D
authors.initials: D
authors.lastname: Variakojis
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: M S
authors.initials: MS
authors.lastname: Tallman
authors.forename: J
authors.initials: J
authors.lastname: Mehta
authors.forename: J N
authors.initials: JN
authors.lastname: Winter
authors.forename: L I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D014182:Transplantation, Autologous