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Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen.
Bone Marrow Transplant. 2004 Apr; 33(8):839-46.BM

Abstract

Cytomegalovirus (CMV) represents a major cause of morbidity after allogeneic stem cell transplantation (allo-SCT). Using interferon-gamma-enzyme-linked immunospot (ELISPOT) assay and HLA-peptide tetramers, we analysed 54 patients who received a reduced-intensity conditioning regimen, including fludarabine, busulphan and antithymocyte globulin (ATG), with the aim of defining essential elements of protective immunity to CMV. The cumulative incidence of CMV positive antigenaemia was 37% occurring at a median of 43 days (range, 7-104) after allo-SCT. In univariate analysis, conditioning regimen (ATG dose) and graft characteristics (graft source and CD3+ T-cell dose) significantly influenced CMV-specific immune recovery. A significant correlation (P=0.000002) was found between CMV-specific T cells detected by IFN-gamma ELISPOT assay and pp65-specific CD8+ T-cell frequency quantified by tetramers. CMV-specific CD8+ T cells presented a phenotype of effector cells (perforin and 2B4 positive). In multivariate analysis, bone marrow (BM) as a graft source was the only variable associated with an increased risk of CMV positive antigenaemia (P=0.0001) in line with the ELISPOT assay showing a higher frequency of functional CMV-specific effectors within peripheral blood stem cell grafts as compared to BM. Thus, early monitoring of CMV-specific immune recovery using sensitive new tools might prove useful for patient management after allo-SCT.

Authors+Show Affiliations

Unité de Transplantation et de Thérapie Cellulaire, Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France. mohtym@marseilles.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14767500

Citation

Mohty, M, et al. "Cytomegalovirus-specific Immune Recovery Following Allogeneic HLA-identical Sibling Transplantation With Reduced-intensity Preparative Regimen." Bone Marrow Transplantation, vol. 33, no. 8, 2004, pp. 839-46.
Mohty M, Mohty AM, Blaise D, et al. Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen. Bone Marrow Transplant. 2004;33(8):839-46.
Mohty, M., Mohty, A. M., Blaise, D., Faucher, C., Bilger, K., Isnardon, D., Sainty, D., Gastaut, J. A., Viens, P., Olive, D., & Gaugler, B. (2004). Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen. Bone Marrow Transplantation, 33(8), 839-46.
Mohty M, et al. Cytomegalovirus-specific Immune Recovery Following Allogeneic HLA-identical Sibling Transplantation With Reduced-intensity Preparative Regimen. Bone Marrow Transplant. 2004;33(8):839-46. PubMed PMID: 14767500.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen. AU - Mohty,M, AU - Mohty,A M, AU - Blaise,D, AU - Faucher,C, AU - Bilger,K, AU - Isnardon,D, AU - Sainty,D, AU - Gastaut,J A, AU - Viens,P, AU - Olive,D, AU - Gaugler,B, PY - 2004/2/10/pubmed PY - 2004/11/13/medline PY - 2004/2/10/entrez SP - 839 EP - 46 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 33 IS - 8 N2 - Cytomegalovirus (CMV) represents a major cause of morbidity after allogeneic stem cell transplantation (allo-SCT). Using interferon-gamma-enzyme-linked immunospot (ELISPOT) assay and HLA-peptide tetramers, we analysed 54 patients who received a reduced-intensity conditioning regimen, including fludarabine, busulphan and antithymocyte globulin (ATG), with the aim of defining essential elements of protective immunity to CMV. The cumulative incidence of CMV positive antigenaemia was 37% occurring at a median of 43 days (range, 7-104) after allo-SCT. In univariate analysis, conditioning regimen (ATG dose) and graft characteristics (graft source and CD3+ T-cell dose) significantly influenced CMV-specific immune recovery. A significant correlation (P=0.000002) was found between CMV-specific T cells detected by IFN-gamma ELISPOT assay and pp65-specific CD8+ T-cell frequency quantified by tetramers. CMV-specific CD8+ T cells presented a phenotype of effector cells (perforin and 2B4 positive). In multivariate analysis, bone marrow (BM) as a graft source was the only variable associated with an increased risk of CMV positive antigenaemia (P=0.0001) in line with the ELISPOT assay showing a higher frequency of functional CMV-specific effectors within peripheral blood stem cell grafts as compared to BM. Thus, early monitoring of CMV-specific immune recovery using sensitive new tools might prove useful for patient management after allo-SCT. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/14767500/Cytomegalovirus_specific_immune_recovery_following_allogeneic_HLA_identical_sibling_transplantation_with_reduced_intensity_preparative_regimen_ L2 - https://doi.org/10.1038/sj.bmt.1704442 DB - PRIME DP - Unbound Medicine ER -