title: Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months.
  
  
  METHODS
  Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine.
  
  
  RESULTS
  All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions +/- chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome.
  
  
  CONCLUSIONS
  The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.
authors.affiliation: Royal Free and UniversityCollege Medical School, Guys Hospital, London, United Kingdom. kirsty.thomson@uclh.nhs.uk
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Thomson
authors.forename: Emma C
authors.initials: EC
authors.lastname: Morris
authors.forename: Adrian
authors.initials: A
authors.lastname: Bloor
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.forename: Don
authors.initials: D
authors.lastname: Milligan
authors.forename: Anne
authors.initials: A
authors.lastname: Parker
authors.forename: Fiona
authors.initials: F
authors.lastname: Clark
authors.forename: Lynny
authors.initials: L
authors.lastname: Yung
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000379:methods*; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan