Betaherpesvirus (Cmv, Hhv-6 and Hhv-7) Active Infections in Brazilian Hematopoietic Stem Cell Transplant Patients

Abstract

Cytomegalovirus (CMV) is one of the most prevalent infectious pathogen in transplant recipients, including those receiving bone marrow or stem cell grafts. Rapid diagnostic tests to identify active CMV infection and preemptive treatment are significant improvements in the management of CMV. Two newly identified beta herpesviruses, human herpesvirus-6 (HHV-6) and human betaherpesvirus-7 (HHV-7), are genetically more closely related to each other than to CMV and have been frequently detected in the blood of allogeneic HSCT. HHV-6 reactivation has been associated with fever, rash, delayed engraftment and encephalitis. Also, HHV-7 has been reported as a cause of severe central nervous system disease and with severe GVHD and sepsis secondary to immune suppression. Nested polymerase chain reaction in blood samples (serum or leukocytes) was used to monitor active CMV, HHV-6 and HHV-7 infections and disease in forty-three HSCT patients for up to 150 days after transplant. All adult recipients with a risk for CMV disease (D+/R+; D+/R-) were enrolled in this study. Acyclovir was used at low doses prior to the transplant as herpes virus prophylactic therapy. Patients who were at least 2 consecutive N-PCR positive for CMV received preemptive therapy with ganciclovir. The prevalence's of positive active CMV, HHV-6 and HHV-7 infections were 72%, 4.6% and 13.9%, respectively. Thirteen patients died (30.2%). Biopsies confirmed CMV disease occurred in 8 out of 43 patients (18.6%), in the gastrointestinal tract. All of them presented active CMV infection and one presented active CMV+HHV-6 infection. None of these patients presented active HHV-7 infection. One patient with CMV disease died by disseminated CMV. Detection of active HHV-6 and HHV-7 infections was low and clinically significant complications were rare. CMV disease remains the most prominent disease associated with HSCT. Results show that surveillance with N-PCR ─ a sensitive, non-invasive and low-cost technique for detection of active beta herpesvirus infections ─ can be used when antigenemia or DNA quantitative methods are unavailable, because patients with a propensity for developing CMV disease can be readily identified and pre-emptive therapy started.

Potency of Various Types of Stem Cells and their Transplantation

“…Transplantation is also limited by mortality of the transplanted cells after transplantation by apoptosis or macrophage activity independent of the autologous or allogeneic procedures used [76]. Cytomegalovirus is one of the most prevalent infectious pathogen in transplant recipients, including those receiving bone marrow or stem cell grafts [77].…”