Effect of Cytomegalovirus (CMV) Serostatus on the Incidence and Virological Features of Active CMV Infection in Allogeneic Stem Cell Transplant Recipients

This is the authors' abstract. We don't add key points for this paper.

TO THE EDITOR—We read with interest the article by Pietersma et al [1]. It was reported that cytomegalovirus (CMV) DNAemia occurred more frequently (P ≤ .001) but was less severe (shorter duration and lower median peak value) in allogeneic stem cell transplant (Allo-SCT) recipients receiving a graft from a CMV-seropositive (D+) donor than in those receiving a graft from a CMV-seronegative donor (D−). Unfortunately, the extensive use of antithymocye globulin in the cohort (60% of patients), which might have been unevenly employed between the D− and D+ groups, may have minimized the well-known impact of receipt of a D+ graft on the early reconstitution of protective CMV-specific T-cell immunity [2–5]. Moreover, it appeared that almost 50% of the patients were not treated with antivirals. This may have introduced a bias in the estimation of the duration of episodes, as the kinetics of plasma CMV DNAemia clearance in self-resolved episodes may differ from that in treated episodes (D. Navarro, unpublished data). We wish to add our experience on this matter. Our analysis focused on a highly homogenous cohort: CMV-seropositive patients (n = 80) undergoing sibling/matched T-cell replete Allo-SCT (D− donors, n = 21; D+ donors, n = 59) at the participating hospitals from December 2006 through January 2010 [3, 5]. Seventy patients were virologically monitored by both the antigenemia pp65 (AG) test and by a plasma real-time polymerase chain reaction (PCR) assay (Abbott Molecular CMV real-time PCR [n = 24]; or Roche LightCycler CMV Quant kit [n = 43]) [5, 6]. These patients were pre-emptively treated with antivirals upon detection of ≥1 pp65-positive cells per 200 000 Polymorphonuclear leukocytes. Thirteen patients were exclusively monitored by the LightCycler CMV Quant kit and treated upon the detection of >500 CMV DNA copies/mL in plasma. A total of 44 patients experienced 1 or more episodes (n = 59) of CMV DNAemia within 6 months after transplantation. All episodes were preemptively treated with antivirals. The CMV DNAemia occurred more frequently in D−/R+ patients than in D+/R+ patients, both within the first 100 days and within 6 months after Allo-SCT, although the differences did not reach statistical significance (Table 1). A trend toward an earlier occurrence of CMV DNAemia was observed in D−/R+ patients. The duration of CMV DNAemia was longer in D−/R+ patients than in D+/R+ patients. The initial and peak CMV DNA loads within the first episode of active CMV infection and the peak value of CMV DNAemia within the study period (considering all episodes) were higher in D−/R+ patients than in D+/R+ patients. The above differences remained when the patients were grouped according to the monitoring strategy and the type of PCR used (data not shown). Recurrent episodes of CMV DNAemia and CMV end-organ disease occurred more frequently in D−/R+ patients than in D+/R+ patients. Our findings are in keeping with previously published data [2–5, 7, 8] indicating that CMV DNAemia develops more frequently and is more severe in D−/R+ Allo-SCT patients than in D+/R+ Allo-SCT patients, irrespective of the transplant modality (T-cell replete or in vivo T-cell depletion with antithymocye globulin) [2, 4], which is related to a delayed reconstitution of CMV-specific T-cell immunity [2, 4, 5]. Demographic and Clinical Data of Allogeneic Stem Cell Transplant Recipients and Virological Features of Episodes of Cytomegalovirus (CMV) DNAemia in the Study Groups NOTE. Data are median or median (range), unless otherwise indicated. Frequency comparisons were performed using the χ2 test (Fisher exact test). Differences between medians were compared using the Mann-Whitney U test (2 independent variables) or the Kruskal-Wallis test (k independent variables). Data were analyzed with the aid of the statistical package SPSS (version 17.0). A P value of <.05 was considered to be statistically significant. Only the cases in which acute graft versus host disease occurred prior to the detection of CMV DNAemia were considered for analysis. Episodes that developed within the first 6 months after transplantation. Episodes that developed within the first 6 months after transplantation in patients completing the follow-up period. (Four patients, 2 D−/R+ and 2 D+/R+, who had not experienced early CMV DNAemia, died prior to the end of the follow-up.) Time elapsed between the first positive and the first negative polymerase chain reaction result (for each episode). Four cases were enteritis and 1 was pneumonitis. Demographic and Clinical Data of Allogeneic Stem Cell Transplant Recipients and Virological Features of Episodes of Cytomegalovirus (CMV) DNAemia in the Study Groups NOTE. Data are median or median (range), unless otherwise indicated. Frequency comparisons were performed using the χ2 test (Fisher exact test). Differences between medians were compared using the Mann-Whitney U test (2 independent variables) or the Kruskal-Wallis test (k independent variables). Data were analyzed with the aid of the statistical package SPSS (version 17.0). A P value of <.05 was considered to be statistically significant. Only the cases in which acute graft versus host disease occurred prior to the detection of CMV DNAemia were considered for analysis. Episodes that developed within the first 6 months after transplantation. Episodes that developed within the first 6 months after transplantation in patients completing the follow-up period. (Four patients, 2 D−/R+ and 2 D+/R+, who had not experienced early CMV DNAemia, died prior to the end of the follow-up.) Time elapsed between the first positive and the first negative polymerase chain reaction result (for each episode). Four cases were enteritis and 1 was pneumonitis. Financial support. This work was supported by Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain (grant 06/1738). Potential conflicts of interest. Rafael de la Cámara has received payment for advisory boards on cytomegalovirus antivirals for Roche. All other authors: No reported conflicts All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed in the Acknowledgments section.