title: Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes.
abstract: The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.
authors.affiliation: Department of Haematology, Royal Free and University College, London, UK. k.peggs@ucl.ac.uk
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Wendi
authors.initials: W
authors.lastname: Qian
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: James
authors.initials: J
authors.lastname: Cavet
authors.forename: Josep M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Anne
authors.initials: A
authors.lastname: Parker
authors.forename: Miguel
authors.initials: M
authors.lastname: Canales
authors.forename: Premini
authors.initials: P
authors.lastname: Mahendra
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Conde
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanz
authors.forename: Kirsty
authors.initials: K
authors.lastname: Thomson
authors.forename: Reyes
authors.initials: R
authors.lastname: Arranz
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: Ivan
authors.initials: I
authors.lastname: Alvarez
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D008727:Methotrexate