Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation

Blood - Tập 116 - Trang 4360-4367 - 2010
Tobias Feuchtinger1, Kathrin Opherk1, Wolfgang A. Bethge2, Max S. Topp3, Friedhelm R. Schuster4, Eva M. Weissinger5, Mohamad Mohty6, Reuven Or7, Michael Maschan8, Michael Schumm1, Klaus Hamprecht9, Rupert Handgretinger1, Peter Lang1, Hermann Einsele3
1Department of Pediatric Hematology/Oncology, University Children's Hospital, Tübingen, Germany;
2Department of Hematology/Oncology, Eberhard-Karls University, Tübingen, Germany;
3Department of Hematology/Oncology, University Hospital Würzburg, Würzburg, Germany;
4Clinic of Pediatric Oncology, Hematology and Immunology, Heinrich-Heine-University, Düsseldorf, Germany;
5Hannover Medical School, Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany;
6Hematologie Clinique, Universite de Nantes, Nantes, France;
7Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel
8Russian Children's Hospital, Moscow, Russia; and
9Institute of Virology, Eberhard-Karls University, Tübingen, Germany

Tóm tắt

Abstract Cytomegalovirus (CMV) disease and infection refractory to antiviral treatment after allogeneic stem cell transplantation (allo-SCT) is associated with a high mortality. Adoptive transfer of CMV-specific T cells could reconstitute viral im-munity after SCT and could protect from CMV-related complications. However, logistics of producing virus-specific T-cell grafts limited the clinical application. We treated 18 patients after allo-SCT from human leukocyte antigen–mismatched/haploidentical or human leukocyte antigen–matched unrelated donors with polyclonal CMV-specific T cells generated by ex vivo stimulation with pp65, followed by isolation of interferon-γ–producing cells. Patients with CMV disease or viremia refractory to antiviral chemotherapy or both were eligible for adoptive T-cell transfer and received a mean of 21 × 103/kg pp65-specific T cells. In 83% of cases CMV infection was cleared or viral burden was significantly reduced, even in cases of CMV encephalitis (n = 2). Viral control was associated with in vivo expansion of CMV-specific T lymphocytes in 12 of 16 evaluable cases, resulting in reconstitution of antiviral T-cell responses, without graft-versus-host disease induction or acute side effects. Our findings indicate that the infusion of low numbers of CMV-specific T cells is safe, feasible, and effective as a treatment on demand for refractory CMV infection and CMV disease after allo-SCT.

Tài liệu tham khảo

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Blood

Tập 116

4360-4367

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