Time of Onset, Viral Load, Relapse, and Duration of Active Cytomegalovirus Infection in Bone Marrow Transplant Outcomes

Abstract

Objectives: Active cytomegalovirus infection remains a major problem for bone marrow transplant recipients. If not quickly diagnosed and treated, it can evolve into cytomegalovirus disease, which represents a life-threatening complication. In this work, we sought to evaluate the interactions between clinical complications after bone marrow transplant and factors associated with active cytomegalovirus infection.

Materials and Methods: We evaluated 91 allogeneic bone marrow transplant recipients (35 female, 56 male; median age, 20 years; age range, 3-47 years) for malignant and nonmalignant hematologic diseases. Active cytomegalovirus infection was monitored using pp65 cytomegalovirus anti­genemia and a semiquantitative cytomegalovirus polymerase chain reaction. Cytomegalovirus end-organ disease was defined as an association between compatible signs and symptoms (dyspnea, hypoxia, and diarrhea) and detection of cyto­megalovirus (≥ 2000 cyto­megalovirus genome copies/mL) by hybrid capture assay in tissue biopsy. Variables were compared using the chi-square and Fisher exact tests. Time of death after bone marrow transplant was plotted using the Kaplan-Meier method. A Cox regression model was used for multivariate survival analysis with 95% confidence limits.

Results: Sixty-four patients experienced active cytomegalovirus infection, 26 had acute graft-versus-host disease, and 11 had cytomegalovirus diseases. The overall survival rate at 4 years was 83.52%. On multivariate analyses, cytomegalovirus disease (hazard ratio = 15.9, P = .001) and age older than 18 years (hazard ratio = 8, P = .18) were the only independent negative prognostic factors for overall survival. Occurrence of acute graft-versus-host disease was increased by early active cytomegalovirus infection (P = .03) and represents a significant factor for active cytomegalovirus infection recurrence (P = .01). Viral load as quantified by antigenemia and cytomegalovirus DNA in the patients’ peripheral blood leukocytes was sig­nificantly associated with clinical complications.

Conclusions: Active cytomegalovirus infection interacts significantly in several ways with graft-versus-host disease and others infections. Acute graft-versus-host disease increases the chances of a poor outcome, especially of acquiring cyto­megalovirus disease. Cytomegalovirus disease constitutes a significant independent risk factor for death after bone marrow transplant.