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, Michael Boeckh

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

Reconstitution of cellular immunity by 3 months after hematopoietic stem cell transplantation (HSCT) is a critical determinant of the long-term success of the transplantation. We analyzed the factors affecting recovery of cytomegalovirus (CMV)-specific CD4+ and CD8+] function at 3 months after HSCT by univariate and multivariable analyses including source of stem cells (bone marrow vs peripheral blood stem cells [PBSCs]), age, sex, graft-versus-host disease (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 less than 100 × 109/L 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 less than 50 × 109/L 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 less than 100 × 109/L and 50 × 109/L, respectively; bone marrow as the source of stem cells; and high-dose steroid use all predict delayed recovery of functional T-cell immunity at 3 months after transplantation. 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.

Original languageEnglish (US)
Pages (from-to)3060-3067
Number of pages8
JournalBlood
Volume102
Issue number8
DOIs
StatePublished - Oct 15 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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