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Antivirals improve CMV pneumonia outcomes after HCT
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Outcomes of cytomegalovirus pneumonia after hematopoietic cell transplantation have improved modestly over the past 25 years largely due to antiviral treatment and changes in transplantation protocols rather than the use of adjunctive immunoglobulin treatment, according to recent findings.
“Although the development of effective cytomegalovirus (CMV) prevention strategies has significantly reduced the need to treat established CMV disease after hematopoietic cell transplantation (HCT), the management of CMV pneumonia remains a formidable challenge,” the researchers wrote. “Furthermore, late CMV disease may occur after both myeloablative and non-myeloablative HCT.”
Michael Boeckh, MD, of the vaccine and infectious disease division of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues examined factors that determine outcome of CMV pneumonia in 421 HCT recipients. Treatment strategies for CMV-seropositive allogeneic HCT recipients have varied over time. For example, in the early 1980s, there was no effective treatment available. When Cytovene (ganciclovir, Hoffmann-La Roche) became available in the mid-1980s, it was adopted as first-line treatment (5 mg/kg every 12 hours for 7 to 21 days as induction therapy followed by 5 mg/kg/day for at least 3 weeks as maintenance therapy). In the event of marrow suppression, Foscavir (foscarnet sodium, Clinigen) was given as a substitute. In the late 1980s, adjunct therapy with pooled immunoglobulin (IVIG) 500 mg/kg or CMV-specific immunoglobulin (CMV-Ig) 150 mg/kg was administered to most patients as adjunct therapy every other day for 2 weeks, followed by a weekly dose for 4 weeks.
Michael Boeckh
In their analysis, the researchers found that at 6 months, the overall survival was 30% (95% CI, 25%-34%). Both all-cause mortality (adjusted HR = 0.7; 95% CI, 0.5-1) and attributed mortality (aHR = 0.6; 95% CI, 0.4-0.9) improved after 2000. Female sex, elevated bilirubin, lymphopenia and mechanical ventilation were independently correlated with an increased risk for both all-cause and attributable mortality. Grade 3-4 acute graft-versus-host disease was correlated with all-cause mortality only.
In an analysis of patients (n = 233) who underwent HCT in the current era of pre-emptive therapy, the researchers found lymphopenia and mechanical ventilation to be the only significant risk factors for overall and attributable death. Antiviral therapy with ganciclovir or foscarnet was associated with improved outcomes compared with no antiviral treatment; however, the adjunctive use of IVIG or CMV-Ig did not improve all-cause or attributable mortality.
“Our results suggest that the introduction of effective antiviral drugs in the late 1980s was an important advance,” the researchers wrote. “This study adds to the controversy regarding the benefit of using immunoglobulin products as adjunct therapy for CMV pneumonia after HTC as it suggests that the benefits are much less impressive than previously reported.”
Boeckh and colleagues said that despite advances in outcomes of CMV pneumonia in the past 25 years, mortality remains too high, and more effective prevention strategies are needed.
Disclosure: Erard reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
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