Alpha/beta T-cell depleted grafts as an immunological booster to treat graft failure after hematopoietic stem cell transplantation with HLA-matched related and unrelated donors.
Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the αβ T-cell receptor and the remaining T-cells express the γδ T-cell receptor. As αβ T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts. The majority of γδ T-cells in the grafts expressed Vδ2 and/or Vγ9. Most patients receiving αβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study.
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Rådestad
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Wikell
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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M
Engström
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Watz
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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B
Sundberg
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Thunberg
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Uzunel
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Mattsson
Department of Oncology and Pathology, Karolinska Institutet, 141 86 Stockholm, Sweden ; Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, 141 86 Stockholm, Sweden ; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 141 86 Stockholm, Sweden.
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Uhlin
D000328:Adult; D001772:Blood Cell Count; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta