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

162 Citations (Scopus)

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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Drug therapy
Hematopoietic Stem Cell Transplantation
Stem cells
Cytomegalovirus
Ganciclovir
Steroids
Drug Therapy
CD4 Lymphocyte Count
Recovery
Bone
Stem Cells
T-cells
Bone Marrow
Transplantation
T-Lymphocytes
Adoptive Immunotherapy
Graft vs Host Disease
Serology
Grafts
Cellular Immunity

ASJC Scopus subject areas

  • Hematology

Cite this

Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation : Impact of host factors, drug therapy, and subclinical reactivation. / Hakki, Morgan; Riddell, Stanley R.; Storek, Jan; Carter, Rachel A.; Stevens-Ayers, Terry; Sudour, Patrick; White, Kristen; Corey, Lawrence; Boeckh, Michael.

In: Blood, Vol. 102, No. 8, 15.10.2003, p. 3060-3067.

Research output: Contribution to journalArticle

Hakki, Morgan ; Riddell, Stanley R. ; Storek, Jan ; Carter, Rachel A. ; Stevens-Ayers, Terry ; Sudour, Patrick ; White, Kristen ; Corey, Lawrence ; Boeckh, Michael. / Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation : Impact of host factors, drug therapy, and subclinical reactivation. In: Blood. 2003 ; Vol. 102, No. 8. pp. 3060-3067.
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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.",
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AU - Carter, Rachel A.

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AU - Sudour, Patrick

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