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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

Bornhäuser et al., Blood. (2011) - PMID: 21540460

Product(s) used in this publication: PepMix™ Peptide Pools

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.

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