Effectiveness of High-Dose Intravenous Acyclovir in Preventing Cytomegalovirus Infection in Allogeneic Stem-Cell Transplantation Recipients: A Retrospective Study in a Medical Center in Singapore

Presenter: Chin Hua Kuan, BSc, BCOP, Singapore General Hospital, National University of Singapore, Singapore

Co-Authors: W. P. Yau, PhD, BSc, National University of Singapore, Singapore; A. Ho, MBBS, MMed, FRCP, FRCPath, Singapore General Hospital, Singapore; Y. C. Linn, MBBS, MRCP, Singapore General Hospital, Singapore; H. Y. Ng, BSc, MSc, BCOP, Singapore General Hospital, Singapore; V. C. Ng, BSc, PharmD, BCOP, Singapore General Hospital, Singapore

BACKGROUND: Cytomegalovirus (CMV) is a significant infection after allogeneic hematopoietic stem-cell transplantation (HSCT). In October 2013, our institution started using prophylactic high-dose intravenous (IV) acyclovir (ie, 500 mg/m² every 8 hours) for patients who underwent allogeneic HSCT. However, an evaluation is warranted because its use is only marginally supported by guidelines.

OBJECTIVE: To evaluate the effectiveness of high-dose IV acyclovir in preventing CMV infection in patients who underwent allogeneic HSCT.

METHOD: A retrospective cohort study was conducted in adult patients who underwent allogeneic HSCT between July 2009 and October 2017 and were CMV-seropositive or had a seropositive donor. Patients admitted between October 2013 and October 2017 who received high-dose IV acyclovir (intervention group) were compared with patients who were admitted between July 2009 and September 2013 (controls). The primary end point was the incidence of clinically significant CMV infection, which was defined as CMV disease or CMV viremia leading to preemptive therapy within 180 days after allogeneic HSCT. Specifically, the incidence of CMV disease was identified. The secondary end points included the time to clinically significant CMV infection, the total number of CMV infection episodes (primary and recurrence), and the 1-year all-cause mortality. Poisson regression was used for the primary outcome analysis.

RESULTS: Of the 146 patients in the high-dose IV acyclovir group, 82 (56.2%) had CMV infection, whereas 116 (73%) of the 159 control patients had CMV infection. The patients who received high-dose IV acyclovir had a 25% reduction in the risk for CMV infection (adjusted relative risk, 0.75; 95% confidence interval, 0.57-1.00; P = .05). The incidence of CMV disease was similar between the groups (4.1% vs 8.8%, respectively; P = .261). The significant differences in the secondary end points that favored the intervention group included the time to clinically significant CMV infection (median, 44 days vs 31 days; interquartile range, [IQR], 39-49 vs 27-35; P = .002) and the total number of CMV infection episodes (median, 1 vs 2; IQR, 1-2 vs 1-2.75; P = .002). However, the 1-year all-cause mortality rate was not statistically significant (27.4% vs 32.1%, respectively; P = .46).

CONCLUSION: High-dose IV acyclovir use was associated with a 25% reduced risk for CMV infection in patients who had allogeneic HSCT, with borderline statistical significance. Although the study was not powered for secondary end points, the time to clinically significant CMV infection and the total number of CMV infection episodes favored the high-dose IV acyclovir group.

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