title: T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma.
abstract: OBJECTIVE
  Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.
  
  
  METHODS
  This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.
  
  
  RESULTS
  With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).
  
  
  CONCLUSIONS
  The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.
authors.affiliation: Department of Haematology, University College Hospital, London, UK. 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: Don
authors.initials: D
authors.lastname: Milligan
authors.forename: Anne N
authors.initials: AN
authors.lastname: Parker
authors.forename: Ann E
authors.initials: AE
authors.lastname: Hunter
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.forename: Adrian J C
authors.initials: AJ
authors.lastname: Bloor
authors.forename: Fiona
authors.initials: F
authors.lastname: Clark
authors.forename: Majid
authors.initials: M
authors.lastname: Kazmi
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; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008224:Lymphoma, Follicular / Q000628:therapy*; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis; D013601:T-Lymphocytes; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents