Background.  Despite major advances in the prevention of cytomegalovirus (CMV) disease, the treatment of CMV pneumonia in recipients of hematopoietic cell transplant remains a significant challenge.

Methods.  We examined recipient, donor, transplant, viral, and treatment factors associated with overall and attributable mortality using Cox regression models.

Results.  Four hundred twenty-one cases were identified between 1986 and 2011. Overall survival at 6 months was 30% (95% confidence interval [CI], 25%–34%). Outcome improved after the year 2000 (all-cause mortality: adjusted hazard ratio [aHR], 0.7 [95% CI, .5–1.0]; P = .06; attributable mortality: aHR, 0.6 [95% CI, .4–.9]; P = .01). Factors independently associated with an increased risk of all-cause and attributable mortality included female sex, elevated bilirubin, lymphopenia, and mechanical ventilation; grade 3/4 acute graft-vs-host disease was associated with all-cause mortality only. An analysis of patients who received transplants in the current preemptive therapy era (n = 233) showed only lymphopenia and mechanical ventilation as significant risk factors for overall and attributable mortality. Antiviral treatment with ganciclovir or foscarnet was associated with improved outcome compared with no antiviral treatment. However, the addition of intravenous pooled or CMV-specific immunoglobulin to antiviral treatment did not seem to improve overall or attributable mortality.

Conclusions.  Outcome of CMV pneumonia showed a modest improvement over the past 25 years. However, advances seem to be due to antiviral treatment and changes in transplant practices rather than immunoglobulin-based treatments. Novel treatment strategies for CMV pneumonia are needed.