title: Donor lymphocyte infusions modulate relapse risk in mixed chimeras and induce durable salvage in relapsed patients after T-cell-depleted allogeneic transplantation for Hodgkin's lymphoma.
abstract: OBJECTIVE
  Reduced-intensity conditioning has minimized nonrelapse-related mortality rates after allogeneic transplantation in patients with Hodgkin's lymphoma, and relapse has now become the major cause for treatment failure. We aimed to assess the impact of donor lymphocyte infusions (DLIs) on relapse incidence when administered for mixed chimerism and their utility as salvage therapy when given for relapse.
  
  
  METHODS
  This study reports the outcomes of 76 consecutive patients with multiply relapsed or refractory Hodgkin's lymphoma who underwent allogeneic transplantation that incorporated in vivo T-cell depletion. Forty-two patients had related donors and 34 had unrelated donors. DLIs were administered in a dose-escalating fashion to 22 patients for mixed chimerism (median time of first dose, 9 months post-transplantation) and to 24 patients for relapse.
  
  
  RESULTS
  Three-year donor lymphocyte-related mortality was 7%, relating mainly to the induction of graft-versus-host disease. Nineteen (86%) of 22 patients receiving donor lymphocytes for mixed chimerism converted to full donor status. Four-year relapse incidence was 5% in these 22 patients compared with 43% in patients who remained relapse free but full donor chimeras at 9 months post-transplantation (P = .0071). Nineteen (79%) of 24 patients receiving donor lymphocytes for relapse responded (14 complete responses, five partial responses). Four-year overall survival from relapse was 59% in recipients of donor lymphocytes, contributing to a 4-year overall survival from transplantation of 64% and a 4-year current progression-free survival of 59% in all 76 patients.
  
  
  CONCLUSIONS
  These data demonstrate the potential for allogeneic immunotherapy with donor lymphocytes both to reduce relapse risk and to induce durable antitumor responses in patients with Hodgkin's lymphoma after hematopoietic stem-cell transplantation that incorporates in vivo T-cell depletion.
authors.affiliation: Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley St, London WC1E 6BT United Kingdom. karl.peggs@cancer.ucl.ac.uk
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.forename: Irfan
authors.initials: I
authors.lastname: Kayani
authors.forename: Noha
authors.initials: N
authors.lastname: Edwards
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kottaridis
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Rachael
authors.initials: R
authors.lastname: Hough
authors.forename: Emma C
authors.initials: EC
authors.lastname: Morris
authors.forename: Adele
authors.initials: A
authors.lastname: Fielding
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Thomson
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006689:Hodgkin Disease / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008131:London; D008212:Lymphocyte Depletion / Q000009:adverse effects / Q000401:mortality; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016879:Salvage Therapy; D015996:Survival Rate; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome; D051598:Whole Body Imaging; D055815:Young Adult