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 immunity 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.
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Authors | Tobias Feuchtinger, Kathrin Opherk, Wolfgang A Bethge, Max S Topp, Friedhelm R Schuster, Eva M Weissinger, Mohamad Mohty, Reuven Or, Michael Maschan, Michael Schumm, Klaus Hamprecht, Rupert Handgretinger, Peter Lang, Hermann Einsele |
Journal | Blood
(Blood)
Vol. 116
Issue 20
Pg. 4360-7
(Nov 18 2010)
ISSN: 1528-0020 [Electronic] United States |
PMID | 20625005
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Phosphoproteins
- Viral Matrix Proteins
- cytomegalovirus matrix protein 65kDa
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Topics |
- Adolescent
- Adoptive Transfer
(methods)
- Adult
- Child
- Child, Preschool
- Cytomegalovirus Infections
(immunology, therapy, virology)
- Feasibility Studies
- Follow-Up Studies
- Haploidy
- Histocompatibility Testing
- Humans
- Middle Aged
- Phosphoproteins
(immunology)
- Recurrence
- Stem Cell Transplantation
- T-Lymphocytes
(immunology, transplantation)
- Time Factors
- Treatment Outcome
- Viral Matrix Proteins
(immunology)
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