title: Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation.
abstract: BACKGROUND
  In patients with multiply relapsed Hodgkin's lymphoma allogeneic stem-cell transplantation has been limited by prohibitive non-relapse-related mortality rates and by a lack of definitive evidence for a therapeutic graft-versus-tumour effect. Therefore, we aimed to assess the graft-versus-tumour effect of reduced-intensity allogeneic transplantation.
  
  
  METHODS
  We undertook reduced-intensity transplantation in 49 patients with multiply relapsed Hodgkin's lymphoma, 44 (90%) of whom had progression of disease after previous autologous transplantation (median age 32 years [range 18-51], number of previous treatment courses was five [range 3-8], and time from diagnosis 4.8 years [range 0.6-4.8]). 31 patients had HLA matched donors who were related and 18 had donors who were unrelated. Median follow-up was 967 days (range 102-2232). The primary endpoints were engraftment, toxic effects, non-relapse-related mortality, incidence of graft-versus-host disease (GVHD), and the toxic effects of adjuvant donor-lymphocyte infusion.
  
  
  RESULTS
  All patients engrafted. Eight of 49 (16%) had grade II-IV acute GVHD and seven (14%) had chronic GVHD before donor-lymphocyte infusion. 16 (33%) patients received donor-lymphocyte infusion from 3 months after transplantation for residual disease or progression. Six (38%) of the 16 developed grade II-IV acute GVHD and five developed chronic GVHD. Nine (56%) showed disease responses after infusion (eight complete, one partial). Non-relapse-related mortality was 16.3% at 730 days (7.2% for patients who had related donors vs 34.1% for those with unrelated donors, p=0.0206). Projected 4 year overall and progression-free survival were 55.7% and 39.0%, respectively (62.0% and 41.5% for related donors).
  
  
  CONCLUSIONS
  These data show the potential for durable responses in patients who have previously had substantial treatment for Hodgkin's lymphoma. The low non-relapse-related mortality suggests the procedure could be undertaken earlier in the course of the disease.
authors.affiliation: Department of Haematology, Royal Free and University College London, UK. kpeggs@hotmail.com
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chopra
authors.forename: Anne
authors.initials: A
authors.lastname: Parker
authors.forename: Premini
authors.initials: P
authors.lastname: Mahendra
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Ruth
authors.initials: R
authors.lastname: Pettengell
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Thomson
authors.forename: Emma C
authors.initials: EC
authors.lastname: Morris
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D006801:Humans; D017710:Lymphocyte Transfusion; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous