Human cytomegalovirus DNAemia and preemptive treatment of CMV infection in children after hematopoietic stem-cell transplantation: Is any question settled?

To the editor:

In a recent issue of Blood, Lilleri et al¹  reported a randomized trial in hematopoietic stem-cell transplantation patients (HSCT) comparing cytomegalovirus (CMV) DNAemia and pp65 antigenemia (Agpp65) as guidance for preemptive treatment. The authors concluded that DNAemia levels of 10 000 CMV genomic copies per milliliter of blood represents an amelioration compared with pp65Ag in terms of reduced number of treated patients and delayed inception of the antiviral therapy. These findings are interesting but some points need to be considered:

(1) The authors stated that no difference was found in the 2 arms of the trial in terms of time of first CMV detection; this result contrasts with the greater sensitivity of the polymerase chain reaction (PCR) method.²  (2) It is not clear whether the criterion to interrupt antiviral therapy was based on negative CMV quantitative PCR (qPCR) or CMV qPCR below the 10 000 CMV genomic copies per milliliter cutoff level. Because the qPCR method has a superior sensitivity, a prolonged DNAemia detection, below the proposed cutoff level for treatment, would be expected in patients on DNAemia arm.³  (3) The authors did not discuss the cases of patients with active CMV replication in which the adaptation of the immunosuppressive regimen (ie, steroid dosage) would have affected the duration of therapy and the number of patients treated. It is well established that steroid treatment is a primary risk factor for increasing CMV antigenemia or DNAemia during preemptive therapy using ganciclovir.⁴  (4) The authors did not discuss that the reduced number of patients preemptively treated and the delayed inception of antiviral therapy found in the DNAemia arm may depend on the different stringency of the cutoff used for antigenemia and DNAemia. (5) The authors stated that the proposed cutoff of 10 000 copies per milliliter of blood should be considered safe as no case of CMV disease was observed. However, the number of patients analyzed was too limited to rule out any risk of CMV disease in HSCT.

Apart from the above considerations, this study provided a significant contribution to optimize the use of quantitative assay for preemptive therapy for CMV.