title: Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T cells after T cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia.
abstract: Donor lymphocyte infusions have been effective in patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation, but their use is associated with the risk of graft-versus-host disease. We investigated the effects of prophylactic infusion of in vitro-generated donor T cells reactive against peptides derived from CML-associated antigens. Fourteen CML patients received conditioning therapy followed by CD34(+)-selected peripheral blood stem cells from matched siblings (n = 7) or unrelated (n = 7) donors. Donor-derived mature dendritic cells generated in vitro from CD14(+) monocytes were loaded with human leukocyte Ag-restricted peptides derived from PR1, WT1, and/or B-cell receptor-ABL and used to repetitively stimulate donor CD8(+) T cells in the presence of IL-2 and IL-7. Stimulated T cells were infused 28, 56, and 112 days after transplantation. Thirteen patients are alive and 7 remain in molecular remission (median follow-up, 45 months). Interestingly, all 4 patients receiving CD8(+) T cells displaying marked cytotoxic activity in vitro and detectable peptide-reactive CD8(+) T cells during follow-up have not experienced graft-versus-host disease or relapse. Our study reveals that prophylactic infusion of allogeneic CD8(+) T cells reactive against peptides derived from CML-associated antigens is a safe and promising therapeutic strategy. This trial was registered at www.clinicaltrials.gov as #NCT00460629.
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital, Dresden, Germany. martin.bornhaeuser@uniklinikum-dresden.de
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiani
authors.forename: Uta
authors.initials: U
authors.lastname: Oelschlaegel
authors.forename: Jana
authors.initials: J
authors.lastname: Babatz
authors.forename: Doris
authors.initials: D
authors.lastname: Lehmann
authors.forename: Kristina
authors.initials: K
authors.lastname: Hölig
authors.forename: Jörgen
authors.initials: J
authors.lastname: Radke
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tuve
authors.forename: Martin
authors.initials: M
authors.lastname: Wermke
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.forename: Hanka
authors.initials: H
authors.lastname: Jähnisch
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bachmann
authors.forename: E Peter
authors.initials: EP
authors.lastname: Rieber
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D003713:Dendritic Cells / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012074:Remission Induction; D016019:Survival Analysis; D014184:Transplantation, Homologous; D025721:WT1 Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D010446:Peptide Fragments; D025721:WT1 Proteins; D016044:Fusion Proteins, bcr-abl; D053146:Myeloblastin