Michael Boeckh, MD; W. Garrett Nichols, MD, MS; Roy F. Chemaly, MD, MPH; Genovefa A. Papanicolaou, MD; John R. Wingard, MD; Hu Xie, MS; Karen L. Syrjala, PhD; Mary E.D. Flowers, MD; Terry Stevens-Ayers, MS; Keith R. Jerome, MD, PhD; Wendy Leisenring, ScD
Acknowledgment: The authors thank all the study patients, participating centers, and study site personnel for their contributions. They thank the participating investigators, research coordinators, and research personnel: Corey Casper, MD, Christi Dahlgren, RN, Louise Kimball, RN, PhD, and David Lew from the Fred Hutchinson Cancer Research Center (Seattle, Washington), as well as Sanam Ara Hussain, Craig Silva, and Zach Stednick (data coordinators); Mark Litzow, MD, from the Mayo Clinic (Rochester, Minnesota); Voravit Ratanatharathorn, MD, from the University of Michigan (Ann Arbor, Michigan); John Zaia, MD, and Ricardo Spielberger, MD, from the City of Hope National Medical Center (Duarte, California); and Nelson Chao, MD, MBA, from Duke University (Durham, North Carolina). The authors also thank the persons who performed virologic testing (Meei-Li Huang, Tracy Santo Hayes, and Linda Cook at the University of Washington) and T-cell immunity testing (Jeremy Smith, Patrick Sudour, Kristen White, Sam Chatterton-Kirchmeier, Tera Matson, and Denise Della at the Fred Hutchinson Cancer Research Center) and the data safety monitoring board (David Snydman, MD [chair]; Richard Whitley, MD; Elizabeth Reed, MD; and Jacqueline Benedetti, PhD [statistician]).
Grant Support: By Roche Laboratories and the National Institutes of Health (grant CA 18029).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2729.
Reproducible Research Statement: Study protocol: Available from Dr. Boeckh (e-mail, firstname.lastname@example.org). Statistical code and data set: Not available.
Current Author Addresses: Dr. Boeckh: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, E4-100, PO Box 19024, Seattle, WA 98109-1024.
Dr. Nichols: GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709.
Dr. Chemaly: University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 402, Houston, TX 77030.
Dr. Papanicolaou: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
Dr. Wingard: University of Florida, 1600 Southwest Archer Road, PO Box 103633, Gainesville, FL 32610-3633.
Ms. Xie and Ms. Leisenring: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2-B230, PO Box 19024, Seattle, WA 98109-1024.
Dr. Syrjala: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D5-220, PO Box 19024, Seattle, WA 98109-1024.
Dr. Flowers: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D5-290, PO Box 19024, Seattle, WA 98109-1024.
Ms. Stevens-Ayers: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, E4-100, PO Box 19024, Seattle, WA 98109-1024.
Dr. Jerome: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, E5-110, PO Box 19024, Seattle, WA 98109-1024.
Author Contributions: Conception and design: M. Boeckh, W.G. Nichols, K.L. Syrjala, W. Leisenring.
Analysis and interpretation of the data: M. Boeckh, W.G. Nichols, R.F. Chemaly, G.A. Papanicolaou, J.R. Wingard, H. Xie, K.L. Syrjala, T. Stevens-Ayers, K.R. Jerome, W. Leisenring.
Drafting of the article: M. Boeckh, W.G. Nichols, M.E.D. Flowers, W. Leisenring.
Critical revision of the article for important intellectual content: M. Boeckh, W.G. Nichols, R.F. Chemaly, G.A. Papanicolaou, J.R. Wingard, K.L. Syrjala, W. Leisenring.
Final approval of the article: M. Boeckh, W.G. Nichols, R.F. Chemaly, G.A. Papanicolaou, J.R. Wingard, K.L. Syrjala, M.E.D. Flowers, K.R. Jerome, W. Leisenring.
Provision of study materials or patients: M. Boeckh, W.G. Nichols, R.F. Chemaly, G.A. Papanicolaou, J.R. Wingard, M.E.D. Flowers, K.R. Jerome.
Statistical expertise: H. Xie, W. Leisenring.
Obtaining of funding: M. Boeckh.
Administrative, technical, or logistic support: T. Stevens-Ayers, K.R. Jerome.
Collection and assembly of data: M. Boeckh, W.G. Nichols, R.F. Chemaly, G.A. Papanicolaou, J.R. Wingard, T. Stevens-Ayers, W. Leisenring.
Optimal prevention of late cytomegalovirus (CMV) disease is poorly defined.
To compare valganciclovir prophylaxis with polymerase chain reaction–guided preemptive therapy.
Randomized, double-blind trial. (ClinicalTrials.gov: NCT00016068)
184 recipients of hematopoietic cell transplantation (HCT) who were at high risk for late CMV disease (95 patients received valganciclovir and 89 received placebo).
6 months of valganciclovir (900 mg/d) or placebo. Patients with polymerase chain reaction positivity at 1000 copies/mL or greater or a 5-fold increase over baseline were treated with ganciclovir or valganciclovir (5 mg/kg or 900 mg twice daily, respectively).
The composite primary end point was death, CMV disease, or other invasive infections by 270 days after HCT. Secondary end points were CMV disease, CMV DNAemia, death, other infections, resource utilization, ganciclovir resistance, quality of life, immune reconstitution, and safety.
The primary composite outcome occurred in 20% of valganciclovir recipients versus 21% of placebo-preemptive therapy recipients (treatment difference, −0.01 [95% CI, −0.13 to 0.10]; P = 0.86). There was no difference in the primary end point or its components 640 days after HCT. The incidence of a CMV DNAemia level of 1000 copies/mL or greater or a 5-fold increase over baseline was reduced in the valganciclovir group (11% vs. 36%; P < 0.001). Neutropenia was not significantly different at the absolute neutrophil count of less than 0.5 × 109 cells/L (P = 0.57); however, more patients received hematopoietic growth factors in the valganciclovir group (25.3% vs. 12.4%; P = 0.026). No significant differences were seen in other secondary outcomes.
Some high-risk patients were not included.
Valganciclovir prophylaxis was not superior in reducing the composite end point of CMV disease, invasive bacterial or fungal disease, or death when compared with polymerase chain reaction–guided preemptive therapy. Both strategies performed similarly with regard to most clinical outcomes.
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Boeckh M, Nichols WG, Chemaly RF, Papanicolaou GA, Wingard JR, Xie H, et al. Valganciclovir for the Prevention of Complications of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Cell Transplantation: A Randomized Trial. Ann Intern Med. 2015;162:1–10. doi: 10.7326/M13-2729
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Published: Ann Intern Med. 2015;162(1):1-10.
Hematology/Oncology, Infectious Disease.
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