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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-03-0993.

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Submitted April 1, 2002
Accepted July 23, 2002

Late cytomegalovirus disease and mortality in allogeneic hematopoietic stem cell transplant recipients: importance of viral load and T-cell immunity

Michael Boeckh*, Wendy Leisenring, Stanley R Riddell, Raleigh A Bowden, Meei-Li Huang, David Myerson, Terry Stevens-Ayers, Mary E D Flowers, Terri Cunningham, and Lawrence Corey

Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA
University of Washington, Seattle, WA, USA
Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

* Corresponding author; email: mboeckh{at}fhcrc.org.

Ganciclovir effectively prevents cytomegalovirus (CMV) disease during the first 100 days after allogeneic hematopoietic stem cell transplantation (HSCT) but late onset CMV disease is increasingly observed. We designed a prospective cohort study to define the incidence and risk factors for late CMV infection in HSCT recipients. CMV seropositive patients were studied prospectively for CMV infection (quantitative pp65 antigenemia, quantitative CMV-DNA, blood culture), T cell immunity (CMV-specific CD4+ T helper and CD8+ cytotoxic T lymphocyte responses, CD4 and CD8 T cell count, absolute lymphocyte count) and other transplant-related factors. Univariate and multivariable analyses were used to assess the risk of late CMV infection, disease, and overall survival. Of 146 patients, 26 (17.8%) developed late CMV disease at a median day 169 after transplant (range 96-784) with a fatality rate of 46%. Thirty-eight percent of patients surviving late disease had a second episode, a median of 79 days after the first episode. At the end of 3 months after transplant, prior detection of CMV pp65 antigenemia, CD4 T cell counts < 50 per mm3, postengraftment absolute lymphopenia < 100 per mm3, undetectable CMV-specific T cell responses, GvHD were associated with late CMV disease or mortality. After 3 months, continued detection of pp65 antigenemia or CMV DNA in plasma or peripheral blood leukocytes as well as lymphopenia (< 300 per mm3) were strong predictors of late CMV disease and mortality. In conclusion, CMV viral load, lymphopenia, and CMV-specific T cell immunodeficiency are predictors of late CMV disease and mortality after allogeneic stem cell transplant. Prevention strategies should be targeted at patients who reactivated CMV during the first 3 months and those with poor CMV-specific immunity or low CD4 counts.


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