ABSTRACT
BACKGROUND: Cytomegalovirus (HCMV) remains an important infection following stem cell transplantation (SCT) and is managed via pre-emptive therapy. In some patients HCMV loads continue to increase after therapy and they experience multiple episodes of replication. OBJECTIVES: To identify the risk factors associated with failure to immediately control HCMV replication after antiviral therapy and for recurrence of replication. STUDY DESIGN: Replication kinetics of human cytomegalovirus (HCMV) were studied a cohort of 153 T-cell depleted allogeneic SCT patients. RESULTS: In 57 patients (31%) who experienced HCMV DNAemia, the mean growth rate of HCMV was 0.35 day(-1) equivalent to a doubling time of 2.2 days. In patients requiring anti-HCMV treatment with either ganciclovir or ganciclovir/foscarnet (n=49), HCMV load increased to a peak value of >2 days after initiation of therapy in 21 patients and only the growth rate prior to therapy was a risk factor (Odds ratio=1.4 per 0.1 day(-1) increase; p=0.004). In patients where antiviral intervention occurred after peak virus load the decline rate of HCMV load was accelerated 4-fold if the patient was subsequently initiated on anti-HCMV therapy (p=0.02). A subset of patients (38%) experienced a recurrence of their DNAemia at a mean of 20 days after the cessation of their first replication episode and this was only associated with receiving stem cells from a seronegative donor (Odds ratio=6.59; p<0.001). CONCLUSIONS: The kinetics of response to therapy is closely associated with HCMV replication kinetics prior to therapy while recurrence of replication is associated with HCMV serostatus of the donor.
Subject(s)
Antiviral Agents/administration & dosage , Cytomegalovirus/drug effects , Ganciclovir/administration & dosage , Stem Cell Transplantation/adverse effects , Virus Replication , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , Child, Preschool , Cytomegalovirus/physiology , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , DNA, Viral/blood , Female , Ganciclovir/therapeutic use , Humans , Kinetics , Male , Middle Aged , Risk Factors , Viral Load , Virus Replication/drug effects , Young AdultABSTRACT
The concept of reduced intensity conditioning (RIC) in allogeneic transplantation had challenged our conventional wisdom about the necessity of high-dose chemo-radiotherapy in order to achieve donor engraftment. The feasibility of RIC in elderly and infirm patients who would not otherwise be considered suitable for a conventional allogeneic transplantation caused a surge of interest in RIC procedures in the late 90s and early part of this decade which was however, not tempered by the balanced need for clinical trials. Although the initial expectations of reduction in graft-versus-host-disease (GVHD) were belied by the high incidences of GVHD, the importance of GVHD, particularly chronic, in controlling haematological malignancies with poor prognosis was often well exemplified. In addition, the conventional outcome measures in allogeneic transplantation such as 100- day mortality became irrelevant in the era of RIC due to reduction in early regimen-related toxicities. This did not always translate to improved overall survival due to late attritions from relapse, GVHD or late infectious complications. The enthusiasm for performing RIC in malignant diseases seems to have reached a plateau, but its true potential probably remains unexplored. In light of our current understanding of RIC, this article will highlight the future of this procedure in haematological malignancies.
Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Animals , Fetal Blood , Graft vs Host Disease , Humans , Transplantation, HomologousABSTRACT
We identified a stem cell donor with chromosomally integrated human herpesvirus (HHV)-6 and monitored the recipient for HHV-6 after transplantation. The appearance and subsequent increase in HHV-6 load paralleled engraftment and an increase in white blood cell count. Fluorescent in situ hybridization analysis showed integrated HHV-6 on chromosome band 17p13.3 in the donor and in the recipient after transplantation but not in the recipient before transplantation. The increase in viral load due to the genetic transmission of integrated HHV-6 could have been misinterpreted as substantial active infection and, thus, led to the administration of toxic antiviral therapy. We suggest that the confounding influence of integration be considered in laboratory investigations associating HHV-6 with disease.
