Abstract: Cytomegalovirus (CMV) reactivation occurs in up to 60% of CMV‐seropositive recipients after allogeneic hematopoietic stem cell transplantation (HSCT). The incidence of CMV disease among T‐cell‐depleted HSCT patients has been reported from 5–15%. The incidence of reactivation refractory to antivirals in this population is not well studied.

Methods. In this retrospective study we characterized the outcome of CMV reactivation in a cohort of 255 adult and pediatric patients who underwent T‐cell‐depleted HSCT at Memorial Sloan‐Kettering Cancer Center from September 1999 through August 2004. CMV infection was monitored by the pp65 antigenemia assay (CMV Ag). Persistent reactivation was defined as antigenemia positivity >21 days on antiviral therapy.

Results. Of 118 CMV‐seropositive recipients, 69 (58.4%) had reactivated CMV. Twenty of 69 (29%) developed persistent reactivation at first episode of reactivation, and 7 (10%) in subsequent episode. All patients with persistent reactivation received ≥2 antivirals and CMV hyperimmune globulin; 45% received combination antiviral therapy. The median duration of persistent reactivation was 98 days, range 31–256 days. In multivariate analysis, maximum CMV Ag >25 cells/slide was associated with persistent reactivation (odds ratio 16.2%, 95% confidence interval 4–64, P<0.0001). CMV disease occurred in 6/27 (22%) patients with persistent reactivation. Patients with persistent reactivation had lower CD4⁺ and CD8⁺ lymphocyte counts compared with those with non‐persistent reactivation at day +90 post HSCT (P=0.01 and 0.02, respectively).

Conclusions. Persistent reactivation occurred in 39% of T‐cell‐depleted HSCT despite treatment with currently available antivirals. Maximum CMV Ag >25 cells/slide was associated with persistent CMV reactivation. More effective treatment modalities are needed for this high‐risk population to reduce CMV‐associated morbidity and mortality.