Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial

Abstract

In the search for better protocols of preemptive therapy of human cytomegalovirus (HCMV) infection in hematopoietic stem cell transplant (HSCT) recipients, we conducted a randomized trial comparing antigenemia with the nucleic acid sequence-based assay (NASBA) for determination of HCMV immediate-early messenger RNA (IEmRNA) as the guiding assay for initiation of pre-emptive antiviral treatment. In the IEmRNA arm, antiviral therapy was started upon IEmRNA positivity confirmed the following day, whereas in the antigenemia arm, therapy was started in the presence of either at least 2 pp65-positive leukocytes/2 ؋ 10 5 examined or a single positive leukocyte confirmed the following day. In both arms, treatment was stopped upon 2 consecutive negative results. All patients were monitored for 3 months after HSCT. The primary end point of the study was duration of anti-HCMV therapy. On the whole, 80 children (41 in the IEmRNA and 39 in the antigenemia arm), recipients of transplants from either a relative or an unrelated donor, completed the study. No patient developed HCMV disease. In the IEmRNA arm, the incidence of HCMV infection was higher compared to the antigenemia arm (80% vs 51%, respectively, P ‫؍‬ .0069), as well as the percentage of treated patients (66% vs 44%, respectively, P ‫؍‬ .045). However, the percentage of relapses and treated relapses was comparable in the 2 arms. There was no significant difference in median duration of therapy per patient. Although these data indicate that IEmRNA determination does not offer advantages in terms of treatment duration, it can safely replace antigenemia, while semiautomation is the major advantage of the NASBA procedure. (Blood. 2003;101:5053-5060)

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

“…However, this finding is to a large extent expected, because of a higher sensitivity of PCR techniques than Antigenemia in detecting active viral replication. 7,14,15,[28][29][30] In addition, relevant changes of patients' characteristics over time led to higher proportion of high-risk patients for CMV-I and CMV-D in the quantPCR period [data not shown], mostly higher proportions of unrelated and mismatched donors (31% in the quantPCR period vs 11% in the pp65Ag period, Po0.01) and in vivo T-cell depleting (20 vs 8%, respectively, Po0.01). 4,9,14,19,31,32 Several observations in this study support that CMV infection and disease are still a frequent and serious complication, with a significant incidence of CMV-D (11%), similar to that observed earlier in alloHSCT-RIC patients.…”

The immunosuppressive effect of human cytomegalovirus infection in recipients of allogeneic hematopoietic stem cell transplantation

“…20 Since, once established, HCMV disease, in particular HCMV-related interstitial pneumonitis, is difficult to treat, it is essential to detect early HCMV infection, either as positive antigenemia, DNAemia, or mRNAemia, and to start antiviral therapy without delay. 14,20,21 Protection from HCMV disease is also dependent on the presence of virus-specific T lymphocytes that, in HSCT rcipients, are predominantly of donor origin. As demonstrated for adult patients given T-cell-depleted HSCT, 22 and recently confirmed in a setting of cord blood transplantation, the residual host-origin, T cells may also play a role in particular contexts.…”

Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection

“…22 Patients were randomized to monitoring of HCMV reactivation by either the antigenemia or the DNAemia assay, according to methods previously described. 20,21 In the antigenemia arm, patients were treated upon first detection of either two or more pp65-positive leukocytes or upon first confirmed positivity, when a single positive cell was detected.…”