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Article: Selective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion

TitleSelective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion
Authors
Keywordshematopoietic cell transplantation
CD45RA depletion
memory T cells
haploidentical donors
T-cell depletion
Issue Date2018
Citation
Transplant Infectious Disease, 2018, v. 20, n. 1, article no. e12823 How to Cite?
Abstract© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. Methods: Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. Results: Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/μL vs 10/μL; P <.001), and higher T-cell diversity by Vbeta spectratyping at Day +100 (P <.001). Importantly, these recipients experienced a significant reduction in both the incidence (P =.002) and duration (P =.02) of any viremia (cytomegalovirus, Epstein-Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3-depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P =.02). Conclusion: CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia.
Persistent Identifierhttp://hdl.handle.net/10722/294521
ISSN
2020 Impact Factor: 2.228
2015 SCImago Journal Rankings: 0.720
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTriplett, Brandon M.-
dc.contributor.authorMuller, Brad-
dc.contributor.authorKang, Guolian-
dc.contributor.authorLi, Ying-
dc.contributor.authorCross, Shane J.-
dc.contributor.authorMoen, Joseph-
dc.contributor.authorCunningham, Lea-
dc.contributor.authorJanssen, William-
dc.contributor.authorMamcarz, Ewelina-
dc.contributor.authorShook, David R.-
dc.contributor.authorSrinivasan, Ashok-
dc.contributor.authorChoi, John-
dc.contributor.authorHayden, Randall T.-
dc.contributor.authorLeung, Wing-
dc.date.accessioned2020-12-03T08:22:55Z-
dc.date.available2020-12-03T08:22:55Z-
dc.date.issued2018-
dc.identifier.citationTransplant Infectious Disease, 2018, v. 20, n. 1, article no. e12823-
dc.identifier.issn1398-2273-
dc.identifier.urihttp://hdl.handle.net/10722/294521-
dc.description.abstract© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. Methods: Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. Results: Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/μL vs 10/μL; P <.001), and higher T-cell diversity by Vbeta spectratyping at Day +100 (P <.001). Importantly, these recipients experienced a significant reduction in both the incidence (P =.002) and duration (P =.02) of any viremia (cytomegalovirus, Epstein-Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3-depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P =.02). Conclusion: CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia.-
dc.languageeng-
dc.relation.ispartofTransplant Infectious Disease-
dc.subjecthematopoietic cell transplantation-
dc.subjectCD45RA depletion-
dc.subjectmemory T cells-
dc.subjecthaploidentical donors-
dc.subjectT-cell depletion-
dc.titleSelective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/tid.12823-
dc.identifier.pmid29178554-
dc.identifier.pmcidPMC5809307-
dc.identifier.scopuseid_2-s2.0-85040739164-
dc.identifier.volume20-
dc.identifier.issue1-
dc.identifier.spagearticle no. e12823-
dc.identifier.epagearticle no. e12823-
dc.identifier.eissn1399-3062-
dc.identifier.isiWOS:000424942800032-
dc.identifier.issnl1398-2273-

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