Late Cytomegalovirus Disease in Marrow Transplantation Is Predicted by Virus Load in Plasma

Abstract

Late occurrence of cytomegalovirus (CMV) disease after day 100 after bone marrow transplantation has become an increasing problem; whether a quantitative measurement of CMV DNA in plasma by polymerase chain reaction (P-PCR) could be predictive of such disease was investigated. In a prospective study, 117 subjects undergoing allogeneic marrow transplantation were followed for 120 days with weekly CMV blood cultures, with day 35 bronchoalveolar lavage CMV cultures, with weekly CMV P-PCR, and with clinical follow-up for an additional 1 -2 years. Despite preemptive ganciclovir, CMV disease occurred in 9% of subjects, with a median time of onset of 176 days. Quantitative CMV P-PCR was associated with the late development of CMV disease (P Å .01). Of 43 subjects with positive P-PCR results, 23% developed CMV disease, but no disease occurred in the 74 subjects with negative P-PCR (P õ .001), despite the fact that 22% had CMV isolated from lung lavage fluid and 32% had CMV isolated from blood. Risk factors for the occurrence of human cytomegalovirusBMT, the presence of CMV DNA in plasma has been associated with risk for disease [3,4, 12] and pulmonary CMV (CMV) -related morbidity after allogeneic bone marrow transplantation (BMT) can be used to guide antiviral therapy [1 -infection [13], but the significance of the quantity of CMV DNA in plasma has not been studied. We evaluated whether 5]. The most important of these factors is the occurrence of asymptomatic CMV reactivation in blood or lung [2], and inquantitative plasma PCR is predictive of late CMV disease. fection of urine or throat has not been as predictive of later disease [1, 2]. In addition, the occurrence of graft-versus-host Methods disease (GVHD), and other factors predisposing to this, such as age ú20 years and HLA mismatch of donor and recipient, Study population. During 1993-1994are important risks for CMV infection and disease [6]. seropositive recipients of allogeneic BMT for hematologic malignancy or severe aplastic anemia were followed for the occurrence With the ability to determine CMV DNA in plasma by polyof CMV infection and disease in a prospective study. CMV infecmerase chain reaction (PCR) [7, 8] persons with CMV pulmonary infection [11]. In allogeneic No clinical decision was made on the basis of CMV P-PCR result. Thirty-six patients (31%) were treated because BAL fluid was positive for CMV; among the 81 BAL fluid CMV-negative subjects, an additional 35 were treated with ganciclovir for positive Received

Incidence of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell recipients at low risk of CMV infection

“…In addition, the semiquantitative PCR of plasma has been previously shown to correlate with the risk of CMV diseases. 7 We do agree with the results reported by Butt and Clark, showing a high frequency of positive surveillance results in low-risk patients, and support the necessity of CMV surveillance. Butt and Clark 1 conclusively recommended the use of CMV antigenemia to monitor CMV infection in lowrisk patients as their results showed a low incidence of CMV disease in spite of the high incidence of CMV infec-tion detected by PCR.…”

Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea

“…[36][37][38] However, recent reports have indicated that most of CMV diseases now develop in the late-recovery phase. 34,35,39 All but one patient in our data had chronic GvHD, an established risk factor for the late CMV disease. We thought that continuous screening of antigenemia should be carried out on patients with a preceding episode of positive result and chronic GvHD.…”

Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT

“…[3][4][5][6]8 These data suggest that the extended AG surveillance performed in our study, may have played an important role in preventing the development of late CMV disease.…”

“…[1][2][3] Both strategies focused on the first 100 days after transplantation and after that most of the published series have screened for CMV infection or disease only in the presence of symptoms. [3][4][5][6][7] Therefore, few surveillance data are available on the occurrence of CMV infection and recurrences after day +100. 8 However, some reports have suggested that the prolonged use of ganciclovir may inhibit the development of CMV-specific T cell responses promoting the occurrence of CMV infection and disease after discontinuation of antiviral therapy.…”