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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4419.

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CORRESPONDENCE

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.

Authorship

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Simone Cesaro, Pediatric Hematology Oncology, Department of Pediatrics, University of Padova, Via Giustiniani 3, Padua PD, Italy 35100; e-mail: simone.cesaro{at}unipd.it.

Simone Cesaro, Davide Abate, and Carlo Mengoli

References

  1. Lilleri D, Gerna G, Furione M, et al. Use of a DNAemia cut-off for monitoring human cytomegalovirus infection reduces the number of preemptively treated children and young adults receiving hematopoietic stem-cell transplantation compared with qualitative pp65 antigenemia. Blood. 2007;110:2757–2760.[Abstract/Free Full Text]

  2. Einsele H, Ehninger G, Hebart H. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood. 1995;86:2815–2820.[Abstract/Free Full Text]

  3. Boeckh M, Bowden RA, Zaja JA. Plasma polymerase chian reaction for cytomegalovirus DNA after allogeneic marrow transplantation: comparison with polymerase chain reaction using peripheral blood leukocytes, pp65 antigenemia, and viral culture. Transplantation. 1997;64:108–113.[CrossRef][Medline] [Order article via Infotrieve]

  4. Nichols WG, Corey L, Gooley T, et al. Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. Blood. 2001;97:867–74.[Abstract/Free Full Text]


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Related Article in Blood Online:

Response: Human cytomegalovirus DNAemia and preemptive treatment of HCMV infection in children receiving hematopoietic stem-cell transplantation
Giuseppe Gerna, Daniele Lilleri, and Franco Locatelli
Blood 2008 111: 4420. [Full Text] [PDF]




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