1. Patient HLA-DP-specific CD4+ T cells from HLA-DPB1-mismatched donor lymphocyte infusion can induce graft-versus-leukemia reactivity in the presence or absence of graft-versus-host disease.
- Author
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Rutten CE, van Luxemburg-Heijs SA, Halkes CJ, van Bergen CA, Marijt EW, Oudshoorn M, Griffioen M, and Falkenburg JH
- Subjects
- CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes pathology, Graft vs Host Disease blood, Graft vs Host Disease pathology, Graft vs Leukemia Effect immunology, HLA-DP beta-Chains blood, Hematologic Neoplasms blood, Hematologic Neoplasms immunology, Hematologic Neoplasms therapy, Humans, Male, Transplantation, Homologous, Tumor Necrosis Factor Receptor Superfamily, Member 9 blood, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology, CD4-Positive T-Lymphocytes metabolism, Graft vs Host Disease immunology, HLA-DP beta-Chains immunology, Stem Cell Transplantation, Unrelated Donors
- Abstract
Clinical studies have demonstrated that HLA-DPB1-mismatched allogeneic stem cell transplantation (allo-SCT) is associated with a decreased risk of disease relapse and an increased risk of graft-versus-host disease (GVHD) compared with HLA-DPB1-matched SCT. In T cell-depleted allo-SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, but a significant decreased risk of disease relapse was still observed. To investigate whether patient HLA-DP-specific CD4(+) T cell responses were frequently induced after T cell-depleted HLA-DPB1-mismatched allo-SCT and donor lymphocyte infusion (DLI), we developed a method to screen for the presence of HLA-DP-specific CD4(+) T cells using CD137 as an activation marker and analyzed 24 patient-donor combinations. The patients suffered from various B cell malignancies, multiple myeloma, and myeloid leukemias. Patient HLA-DP-specific CD4(+) T cells were detected after DLI in 13 of 18 patients who exhibited a clinical response to DLI, compared with only 1 of 6 patients without a clinical response to DLI. Eight patients developed significant GVHD. These data show that patient HLA-DP-specific CD4(+) T cells frequently occur after HLA-DPB1-mismatched T cell-depleted allo-SCT and DLI, and are associated with graft-versus-leukemia reactivity both in the presence and absence of GVHD., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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