 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 February 1993 | Volume 118 Issue 3 | Pages 179-184
Objective: To evaluate the efficacy and safety of ganciclovir for prevention of cytomegalovirus (CMV) infection and disease.
Design: A randomized, placebo-controlled, double-blind trial.
Setting: University-affiliated bone marrow transplant center.
Patients: Cytomegalovirus-seropositive allogeneic bone marrow transplant recipients.
Interventions: Random assignment to receive either a placebo or ganciclovir at a dose of 2.5 mg/kg body weight every 8 hours for 1 week before transplant and then at a dose of 6 mg/kg once per day, Monday through Friday, after transplant when the post-transplant neutrophil count reached 1.0 x 109/L.
Measurements: Cytomegalovirus infection (positive culture, seroconversion, positive histologic findings), CMV disease (pneumonia, gastroenteritis, the wasting syndrome), and study-drug toxicity.
Results: Cytomegalovirus infection developed in 25 of 45 placebo patients (56%) but in only 8 of 40 ganciclovir patients (20%) (P < 0.001). Cytomegalovirus disease may also have occurred less often in the ganciclovir patients (4 of 40 patients [10%] versus 11 of 45 patients [24%]; P = 0.09). The probability of CMV disease occurring within the first 120 days after transplantation was 0.29 among the placebo patients but only 0.12 among ganciclovir patients (P = 0.06). Reversible neutropenia was the only appreciable toxicity related to ganciclovir and required interruption of the study drug after transplant in 25 of 43 ganciclovir patients (58%) and in 13 of 47 placebo patients (28%) (P = 0.005). Overall survival was similar in both the placebo patients (29 of 45 [64%]) and ganciclovir patients (28 of 40 [70%]; P > 0.2).
Conclusions: Prophylactic ganciclovir, started before transplant and continued after recovery of the post-transplant neutrophil count, reduces the incidence and severity of CMV infection in CMV-seropositive bone marrow transplant recipients but is frequently associated with neutropenia.
Author and Article Information
From the UCLA Center for the Health Sciences, Los Angeles, California; the Institute of Clinical Medicine, Syntex Research, Palo Alto, California.
ARTICLE
Ganciclovir Prophylaxis of Cytomegalovirus Infection and Disease in Allogeneic Bone Marrow Transplant Recipients: Results of a Placebo-Controlled, Double-Blind Trial
Requests for Reprints: Drew J. Winston, MD, Room 42-121 CHS, Department of Medicine, UCLA Medical Center, Los Angeles, CA 90024.
Acknowledgments: The authors thank Marjorie J. Miller, DPH, David A. Bruckner, ScD, and the staff of the UCLA Clinical Microbiology Laboratories for technical assistance; Bill Hirokawa, Ed Arriola, and the staff of the UCLA Pharmacy Services for administrative assistance; Margaret Frane for statistical assistance; Katharine Fry for preparation of the manuscript; and the nursing staffs who assisted in the care of these patients. The authors also thank Dr. Stephen Feig for his assistance and cooperation.
Grant Support: By grant CA-23175 from the National Cancer Institute and by a research grant from Syntex Research.
This article has been cited by other articles:
|
|
 |
|
  D. J. Winston, J.-A. H. Young, V. Pullarkat, G. A. Papanicolaou, R. Vij, E. Vance, G. J. Alangaden, R. F. Chemaly, F. Petersen, N. Chao, et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study Blood, June 1, 2008; 111(11): 5403 - 5410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Marty, J. Bryar, S. K. Browne, T. Schwarzberg, V. T. Ho, I. V. Bassett, J. Koreth, E. P. Alyea, R. J. Soiffer, C. S. Cutler, et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis Blood, July 15, 2007; 110(2): 490 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Albano, P. Taylor, R. F. Pass, A. Scaradavou, R. Ciubotariu, C. Carrier, L. Dobrila, P. Rubinstein, and C. E. Stevens Umbilical cord blood transplantation and cytomegalovirus: posttransplantation infection and donor screening Blood, December 15, 2006; 108(13): 4275 - 4282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Einsele, P. Reusser, M. Bornhauser, P. Kalhs, G. Ehninger, H. Hebart, Y. Chalandon, N. Kroger, B. Hertenstein, F. Rohde, et al. Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation Blood, April 1, 2006; 107(7): 3002 - 3008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ljungman, R. Brand, H. Einsele, F. Frassoni, D. Niederwieser, and C. Cordonnier Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis Blood, December 15, 2003; 102(13): 4255 - 4260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Meijer, G. J. Boland, and L. F. Verdonck Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants Clin. Microbiol. Rev., October 1, 2003; 16(4): 647 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Papanicolaou, J.-B. Latouche, C. Tan, J. Dupont, J. Stiles, E. G. Pamer, and M. Sadelain Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele Blood, October 1, 2003; 102(7): 2498 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cordonnier, S. Chevret, M. Legrand, H. Rafi, N. Dhedin, B. Lehmann, F. Bassompierre, E. Gluckman, and for the GREFIG Study Group* Should Immunoglobulin Therapy Be Used in Allogeneic Stem-Cell Transplantation? A Randomized, Double-Blind, Dose Effect, Placebo-Controlled, Multicenter Trial Ann Intern Med, July 1, 2003; 139(1): 8 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boeckh, W. Leisenring, S. R. Riddell, R. A. Bowden, M.-L. Huang, D. Myerson, T. Stevens-Ayers, M. E. D. Flowers, T. Cunningham, and L. Corey Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity Blood, January 15, 2003; 101(2): 407 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ozdemir, L. S. St. John, G. Gillespie, S. Rowland-Jones, R. E. Champlin, J. J. Molldrem, and K. V. Komanduri Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells Blood, November 15, 2002; 100(10): 3690 - 3697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Wagner, J. N. Barker, T. E. DeFor, K. S. Baker, B. R. Blazar, C. Eide, A. Goldman, J. Kersey, W. Krivit, M. L. MacMillan, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival Blood, August 13, 2002; 100(5): 1611 - 1618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Tabbara, K. Zimmerman, C. Morgan, and Z. Nahleh Allogeneic Hematopoietic Stem Cell Transplantation: Complications and Results Arch Intern Med, July 22, 2002; 162(14): 1558 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Macha and A. K. Mitra Ocular Disposition of Ganciclovir and Its Monoester Prodrugs following Intravitreal Administration Using Microdialysis Drug Metab. Dispos., June 1, 2002; 30(6): 670 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Berger and W. Preiser Viral genome quantification as a tool for improving patient management: the example of HIV, HBV, HCV and CMV J. Antimicrob. Chemother., June 1, 2002; 49(5): 713 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Reusser, H. Einsele, J. Lee, L. Volin, M. Rovira, D. Engelhard, J. Finke, C. Cordonnier, H. Link, and P. Ljungman Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation Blood, February 15, 2002; 99(4): 1159 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Griffiths The treatment of cytomegalovirus infection J. Antimicrob. Chemother., February 1, 2002; 49(2): 243 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Szmania, A. Galloway, M. Bruorton, P. Musk, G. Aubert, A. Arthur, H. Pyle, N. Hensel, N. Ta, L. Lamb Jr, et al. Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers Blood, August 1, 2001; 98(3): 505 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Cwynarski, J. Ainsworth, M. Cobbold, S. Wagner, P. Mahendra, J. Apperley, J. Goldman, C. Craddock, and P. A. H. Moss Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation Blood, March 1, 2001; 97(5): 1232 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Peggs, S. Verfuerth, and S. Mackinnon Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions Blood, February 15, 2001; 97(4): 994 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Boivin, R. Bélanger, R. Delage, C. Béliveau, C. Demers, N. Goyette, and J. Roy Quantitative Analysis of Cytomegalovirus (CMV) Viremia Using the pp65 Antigenemia Assay and the COBAS AMPLICOR CMV MONITOR PCR Test after Blood and Marrow Allogeneic Transplantation J. Clin. Microbiol., December 1, 2000; 38(12): 4356 - 4360. [Abstract] [Full Text]
|
|
|
|
|
|
Management of herpes virus infections following transplantation J. Antimicrob. Chemother., June 1, 2000; 45(6): 729 - 748. [Full Text] [PDF]
|
|
|
|
|
|
A. E. C. Broers, R. van der Holt, J. W. J. van Esser, J.-W. Gratama, S. Henzen-Logmans, V. Kuenen-Boumeester, B. Lowenberg, and J. J. Cornelissen Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation Blood, April 1, 2000; 95(7): 2240 - 2245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Sun, K. E. Pollok, R. L. Burton, L. J. Dai, W. Britt, D. J. Emanuel, and K. G. Lucas Simultaneous Ex Vivo Expansion of Cytomegalovirus and Epstein-Barr Virus-Specific Cytotoxic T Lymphocytes Using B-Lymphoblastoid Cell Lines Expressing Cytomegalovirus pp65 Blood, November 1, 1999; 94(9): 3242 - 3250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Salzberger, R. A. Bowden, R. C. Hackman, C. Davis, and M. Boeckh Neutropenia in Allogeneic Marrow Transplant Recipients Receiving Ganciclovir for Prevention of Cytomegalovirus Disease: Risk Factors and Outcome Blood, September 15, 1997; 90(6): 2502 - 2508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Reusser, R. Attenhofer, H. Hebart, C. Helg, B. Chapuis, and H. Einsele Cytomegalovirus-Specific T-Cell Immunity in Recipients of Autologous Peripheral Blood Stem Cell or Bone Marrow Transplants Blood, May 15, 1997; 89(10): 3873 - 3879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Nash, T. Gooley, C. Davis, and F. R. Appelbaum The Problem of Thrombocytopenia after Hematopoietic Stem Cell Transplantation Oncologist, December 1, 1996; 1(6): 371 - 380. [Abstract] [Full Text] [PDF]
|
|
Article
