Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes.
To determine the risk factors and outcomes associated with rising cytomegalovirus (CMV) antigenemia levels during preemptive therapy among stem cell allograft recipients, 119 patients with CMV antigenemia were studied. Patients were prospectively monitored for CMV antigenemia weekly; those with positive findings on antigenemia tests were treated with intravenous ganciclovir (5 mg/kg twice daily for 1 week, followed by 5 mg/kg per day for 5-6 d/wk). While on therapy, 47 of 119 (39%) patients demonstrated increases that were 2 or more times greater than their baseline values, whereas 33 of 119 (28%) patients demonstrated increases that were 5 or more times greater. Rising antigenemia was confirmed by polymerase chain reaction for CMV DNA. Multivariate analysis identified corticosteroids as the primary risk factor for increasing antigenemia: for increases greater than or equal to twice the baseline, 1 to 2 mg/kg steroids was associated with an odds ratio (OR) of 4.0. For increases greater than or equal to 2 mg/kg steroids, the OR was 10.1. CMV isolates obtained at the time of rising antigenemia were susceptible to ganciclovir, indicating that resistance was not a major factor. Overall, rising antigenemia levels were not correlated with CMV disease. All 4 patients in whom CMV disease developed during therapy, however, had rising antigenemia levels. Among the 47 patients with antigenemia increases greater than or equal to twice the baseline, 15 were re-induced with antivirals, whereas 32 continued to receive maintenance therapy. All 4 patients in whom CMV disease developed during therapy received maintenance therapy, and 3 died with CMV disease. Thus, host factors such as the receipt of corticosteroids explain increasing viral load during the early phase of preemptive therapy. Continued induction dosing or re-induction may protect against early breakthrough CMV disease and CMV-related death among patients with rising antigenemia on preemptive therapy. (Blood. 2001;97:867-874)
Nichols
W G
WG
Fred Hutchinson Cancer Research Center Program in Infectious Diseases and the University of Washington, Seattle, WA, USA.
Corey
L
L
Gooley
T
T
Drew
W L
WL
Miner
R
R
Huang
M
M
Davis
C
C
Boeckh
M
M
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000188:drug therapy / Q000209:etiology / Q000635:transmission; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects*; D016896:Treatment Outcome; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000097:blood*; D014766:Viremia / Q000097:blood*; D014775:Virus Activation
D000305:Adrenal Cortex Hormones; D000956:Antigens, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D017245:Foscarnet; D015774:Ganciclovir