Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation.
Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC) <or=1500 x 10(6)/l at randomization (P < 0.01) and grade II-IV acute graft-versus-host-disease (P = 0.01), but not the assigned prophylaxis cohort (P = 0.62), were independent risk factors for CMV disease. The incidence of fungal infections and renal insufficiency was similar across treatment groups; however, bacterial infections and secondary neutropenia occurred more frequently in the ganciclovir group. With our study powered to detect a 60% reduction in antigenemia with ganciclovir prophylaxis, we did not find a statistically significant difference between ganciclovir and acyclovir when used as part of an overall strategy for prevention of CMV antigenemia and disease in SCT, although fewer side-effects occurred with acyclovir treatment.
Burns
L J
LJ
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
Miller
W
W
Kandaswamy
C
C
DeFor
T E
TE
MacMillan
M L
ML
Van Burik
J-A
JA
Weisdorf
D J
DJ
D000212:Acyclovir / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D007223:Infant; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D009503:Neutropenia / Q000150:complications; D011446:Prospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects*; D016896:Treatment Outcome; D014766:Viremia / Q000517:prevention & control*; D017735:Virus Latency; D014779:Virus Replication
D000956:Antigens, Viral; D015774:Ganciclovir; D000212:Acyclovir