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.
journal_name
Bloodjournal_title
Bloodauthors
Bornhäuser M,Thiede C,Platzbecker U,Kiani A,Oelschlaegel U,Babatz J,Lehmann D,Hölig K,Radke J,Tuve S,Wermke M,Wehner R,Jähnisch H,Bachmann MP,Rieber EP,Schetelig J,Ehninger G,Schmitz Mdoi
10.1182/blood-2010-09-308569subject
Has Abstractpub_date
2011-06-30 00:00:00pages
7174-84issue
26eissn
0006-4971issn
1528-0020pii
blood-2010-09-308569journal_volume
117pub_type
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