SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-11-3472. This Article Full Text (PDF) All Versions of this Article: 2002-11-3472v1 102/8/3060    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hakki, M. Articles by Boeckh, M. Search for Related Content PubMed PubMed Citation Articles by Hakki, M. Articles by Boeckh, M. Social Bookmarking                   What's this? Submitted November 15, 2002 Accepted June 8, 2003 Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation Morgan Hakki, Stanley R Riddell, Jan Storek, Rachel A Carter, Terry Stevens-Ayers, Patrick Sudour, Kristen White, Lawrence Corey, and Michael Boeckh* Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA * Corresponding author; email: mboeckh{at}fhcrc.org. Reconstitution of cellular immunity by three months after hematopoietic stem cell transplantation (HSCT) is a critical determinant of the long-term success of the transplant. We analyzed the factors affecting recovery of CMV-specific CD4+ and CD8+ function at 3 months after HSCT by univariate and multivariable analyses, including source of stem cells (bone marrow vs. PBSC), age, gender, GVHD, steroid use, conditioning regimens, ganciclovir use, HLA matching, circulating CMV antigenemia, absolute CD4+ and CD8+ counts, and donor CMV serology. High dose steroids and CD4+ count <100/mm3 were significant predictors of impaired CD4+ functional recovery in the multivariable analysis. High dose steroids, bone marrow as a source of stem cells, and CD8+ count <50/mm3 were associated with impaired CD8+ function in the multivariable analysis. Steroids were found to impair both CD4+ and CD8+ function in a dose-dependent manner. In the absence of high-dose steroids, low-level subclinical CMV antigenemia was found to stimulate both CD4+ and CD8+ functional recovery in recipients of ganciclovir prophylaxis. There was no difference in immune reconstitution between those who received prophylactic ganciclovir versus antigenemia-guided pre-emptive therapy. Thus, absolute CD4+ and CD8+ counts <100/mm3 and 50/mm3, respectively, bone marrow as the source of stem cells, and high-dose steroid use all predict delayed recovery of functional T-cell immunity at three months after transplant. Subclinical CMV reactivation while on ganciclovir appears to be a potent stimulator of T-cell function. These findings have implications for vaccination and adoptive-immunotherapy strategies in this population. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Lilleri, C. Fornara, A. Chiesa, D. Caldera, E. P. Alessandrino, and G. Gerna Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection Haematologica, February 1, 2008; 93(2): 248 - 256. [Abstract] [Full Text] [PDF] E. Castermans, F. Baron, E. Willems, N. Schaaf-Lafontaine, N. Meuris, A. Gothot, J.-F. Vanbellighen, C. Herens, L. Seidel, V. Geenen, et al. Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning Haematologica, February 1, 2008; 93(2): 240 - 247. [Abstract] [Full Text] [PDF] F. M. Marty, J. Bryar, S. K. Browne, T. Schwarzberg, V. T. Ho, I. V. Bassett, J. Koreth, E. P. Alyea, R. J. Soiffer, C. S. Cutler, et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis Blood, July 15, 2007; 110(2): 490 - 500. [Abstract] [Full Text] [PDF] D. M. Hockenbery, S. Cruickshank, T. C. Rodell, T. Gooley, F. Schuening, S. Rowley, D. David, M. Brunvand, B. Berryman, S. Abhyankar, et al. A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease Blood, May 15, 2007; 109(10): 4557 - 4563. [Abstract] [Full Text] [PDF] J. C. Wade Viral Infections in Patients with Hematological Malignancies Hematology, January 1, 2006; 2006(1): 368 - 374. [Abstract] [Full Text] [PDF] J. D. Roback Vaccine-Enhanced Donor Lymphocyte Infusion (veDLI) Hematology, January 1, 2006; 2006(1): 486 - 491. [Abstract] [Full Text] [PDF] Y. Chalandon, S. Degermann, J. Villard, L. Arlettaz, L. Kaiser, S. Vischer, S. Walter, M. H. M. Heemskerk, R. A. W. van Lier, C. Helg, et al. Pretransplantation CMV-specific T cells protect recipients of T-cell-depleted grafts against CMV-related complications Blood, January 1, 2006; 107(1): 389 - 396. [Abstract] [Full Text] [PDF] V. Erard, H. W. Kim, L. Corey, A. Limaye, M.-L. Huang, D. Myerson, C. Davis, and M. Boeckh BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients Blood, August 1, 2005; 106(3): 1130 - 1132. [Abstract] [Full Text] [PDF] Z. Wang, C. La Rosa, S. Mekhoubad, S. F. Lacey, M. C. Villacres, S. Markel, J. Longmate, J. D. I. Ellenhorn, R. F. Siliciano, C. Buck, et al. Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells Blood, August 1, 2004; 104(3): 847 - 856. [Abstract] [Full Text] [PDF] M. Boeckh and W. G. Nichols The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy Blood, March 15, 2004; 103(6): 2003 - 2008. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020