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

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, HILA 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. (Blood. 2003; 102:3060-3067). (C) 2003 by The American Society of Hematology.