Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation.

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 x 10(9)/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 x 10(9)/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 x 10(9)/L and 50 x 10(9)/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.

• Authors: Morgan Hakki, Stanley R Riddell, Jan Storek, Rachel A Carter, Terry Stevens-Ayers, Patrick Sudour, Kristen White, Lawrence Corey, Michael Boeckh
• Journal: Blood (Blood) Vol. 102 Issue 8 Pg. 3060-7 (Oct 15 2003) ISSN: 0006-4971 [Print] United States
• PMID: 12843000 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Ganciclovir

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (therapeutic use)
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Child
• Child, Preschool
• Cytomegalovirus (metabolism)
• Cytomegalovirus Infections (prevention & control)
• Dose-Response Relationship, Drug
• Female
• Ganciclovir (therapeutic use)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Infant
• Lymphocytes (metabolism)
• Male
• Middle Aged
• Multivariate Analysis
• Time Factors
• Transplantation Conditioning
• Transplantation, Homologous (methods)