CMV antigenemia following pediatric hematopoietic stem cell transplantation:risk factors and outcomes / 소아과

PURPOSE: Cytomegalovirus(CMV) infection still remains as a major cause of morbidity and mortality after stem cell transplantation. In this study, we analyzed the results of antigenemia-guided pre-emptive therapy among children with allogeneic hematopoietic stem cell transplantation to determine the incidence and risk factors associated with CMV antigenemia, and evaluated the efficacy of the CMV antigenemia based preemptive therapy. METHODS: We enrolled 213 pediatric patients following allogeneic hematopoietic stem cell transplantation(HSCT), at the Catholic HSCT center between October 1998 and December 2003. Pre-emptive ganciclovir was started when more than 5 CMV Ag-positive cells were detected in matched sibling HSCT, and when any Ag-positive cells were seen in unrelated allogenic HSCT. RESULTS: CMV antigenemia was observed in 88(41.3 percent) of 213 patients on median day 28(day 11-99). In univariated analysis, use of unrelated donors(other than siblings), age of recipient(more than 5 years at transplant) at transplantation, the presence of recipient CMV-IgG before transplantation, TBI-based conditioning regimen and the presence of acute GvHD(grade > or=II) were the risk factors for positive CMV antigenemia. In multivariate analysis, unrelated bone marrow transplantation, positive recipient CMV serology and acute GvHD(grade > or=II) were the independent risk factors for positive CMV antigenemia. CONCLUSION: Risk factors of CMV infection in children were CMV serostatus of the recipient, the source of stem cells, and acute graft-versus-host disease. The pre-emptive therapy based on CMV antigenemia was effective in the prevention of CMV disease.

The Effect of Preemptive Therapy with Intravenous Ganciclovir Followed by Oral Ganciclovir against Cytomegalovirus Infection after Allogeneic Peripheral Blood Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Recently, in vitro studies demonstrated faster immune reconstitution after allogeneic peripheral blood stem cell transplantation (PBSCT) compared to bone marrow transplantation (BMT). In consequence, it can be expected that better immune reconstitution against cytomegalovirus (CMV) will lead to a reduced CMV-related morbidity and mortality after allogeneic PBSCT. METHODS: Forty seven patients who received allogeneic PBSCT were enrolled. CMV was routinely sought by at least weekly screening for CMV-related matrix protein pp65 antigenemia after engraftment (WBC >1,500/nL) was achieved. CMV antigenemia was treated with ganciclovir 5mg/kg twice daily i.v. as preemptive therapy for at least 10 days. After then, ganciclovir i.v. was switched to oral ganciclovir for maintenance therapy. RESULTS: CMV antigenemia was detected 8 (17%) out of 47 patients and CMV disease developed in only 1 case (2.1%). The medianperiod of time until the detection of CMV antigenemia was 51.5 days (range, 35~230). In 7 out of 8 cases, CMV antigenemia disappeared with ganciclovir treatment in 7 days. One patient with CMV disease (CMV interstitial pneumonitis) showed persistent CMV antigenemia for 3 months and expired due to restrictive lung disease. CONCLUSION: The incidence of CMV antigenemia and resistance to ganciclovir treatment was lower than the incidence of those reported in allogeneic BMT trials. These findings suggest that faster immune reconstitution against CMV after allogeneic PBSCT might have a stronger role in the prevention of emergence of CMV antigenemia and ganciclovir treatment than after allogeneic BMT.

Comparison of Polymerase Chain Reaction Method and CMV Antigenemia Assay for Diagnosis of Cytomegalovirus Infection in Transplanted Patients / 대한임상미생물학회지

BACKGROUND: Early detection and treatment of cytomegalovirus (CMV) infection is very important because CMN infection is a major cause of morbidity and mortality after organ transplantation. CMV antigenemia assay has been reported to be very sensitive and specific for detection of CMV infection among many laboratory methods. However, there is no single method correlated well with the infection state up to now. We compared the results of SHARP Signal System Assay (Digene, USA) using PCR and hybridization with those of CMV antigenemia assay (Clonab CMV-kit; Biotest AG, Germany) to evaluate their clinical usefulness. METHODS: We performed SHARP Signal Assay on whole blood samples of 125 from 56 transplanted patients submitted for CMV antigenemia at Samsung Medical Center. We compared the results with those of CMV antigenemia and evaluated the correlation with CMV disease state. RESULTS: Fifty six patients were classified as three groups; 43 patients with no evidence of CMV infection, four patients with CMV infection and 9 patients with CMV disease. Twenty four cases (19.2%) showed discrepant results between the two methods. Of the 22 cases showing positive only by SHARP Signal Assay, two cases were proved to be CMV disease, 12 cases were on antiviral treatment and remaining cases had no evidence of infection. Two cases showing positive only by CMV antigenemia were confirmed to be CMV disease. For CMV disease, the sensitivity of SHARP Signal Assay and CMV antigenemia were 85.7% and 90.5%, respectively and the specificity of them were 73.1% and 93.3%, respectively. CONCLUSIONS: CMV antigenemia is thought to be useful for early diagnosis and follow-up of antiviral treatment as a quantitative and highly specific method, and SHARP Signal Assay can be used as a complementary method because it correlates well with disease state.

Comparison of Cytomegalovirus Antigenemia with Roche Amplicor CMV test for Detection of Cytomegalovirus Infection in Bone Marrow Transplant Recipients / 대한임상병리학회지

BACKGROUND: CMV Antigenemia (CMV-Ag) assay and polymerase chain reaction (PCR) have been introduced as exponents of a new generation of tests for the detection of CMV infection. So we compared Roche Amplicor test with CMV-Ag assay to evaluate their clinical usefulness. METHODS: CMV-Ag assay using CMV-vueTM kit (INCSTAR Co., U.S.A.) detects pp65 antigen in leukocytes by immunoperoxidase detection system (positive; stained nucleus > OR =1). Amplicor CMV test (Roche Diagnostic Systems, Inc., Branching, NJ, USA) using plasma or serum is based on PCR amplification of target DNA using CMV specific biotinylated primer and hybridization of the amplified products to the probe and subsequent colorimetric detection of amplified DNA. RESULTS: Of the bone marrow transplanted 73 cases, eleven cases showed discrepancy between the two methods. Of these 10 cases those showed positive results only by Amplicor CMV test, 9 cases turned out to be true positive by the follow-up test and clinical manifestation. And the remaining one case was thought to be false positive. One case which showed positive result only by CMV-Ag assay was proved to be true positive. Consequently, CMV-Ag assay had sensitivity of 73.5% and specificity of 100%, Amplicor CMV test had 97.1% and 97.4%, respectively. Amplicor CMV test detected CMV DNA average 16.3 days before the onset of clinical manifestation and sustained until 10 days after symptoms disappearance, otherwise CMV-Ag assay detected mean 3.8 days earlier and sustained 4.2 days after. CONCLUSIONS: Amplicor CMV test is more sensitive, rapid and longer sustained method than CMV-Ag assay but it lacks quantitation.