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The effect of quantification standards used in real-time CMV PCR assays on guidelines for initiation of therapy in allogeneic stem cell transplant patients

Bone Marrow Transplantation volume 39, pages 237–238 (2007)Cite this article

Reactivation of a latent cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) patients. Quantitative polymerase chain reaction (qPCR) assays and the CMV pp65 antigenemia test are used commonly to detect reactivation of CMV and guide pre-emptive therapy before disease onset.1, 2, 3 Although qPCR assays are gaining popularity, guidelines for antiviral therapy based on these results are lacking. The CDC, Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation guidelines published in the year 2000, mention only non-quantitative PCR.4 Different institutions have developed their own assays and local guidelines, and these vary depending on the specimen type (whole blood, plasma or a leukocyte preparation) and the design of the assay. Approaches have included treatment after one5 or two positive PCR tests,3 when the CMV viral load reaches a threshold value6, or a combination of these.7

The recent publication by Verkruyse et al.6 of their experience and recommendations at the Washington University School of Medicine, clearly different from that of the National Institutes of Health Clinical Research Center (NIH), prompted us to undertake the present study. At the Washington University School of Medicine, it has been recommended that for recipients of nonmyeloablative allogeneic stem cell transplants once daily ganciclovir should be initiated when a threshold CMV viral load reached 104 copies/ml of whole blood.6 This recommendation was based in part on the observation that symptomatic disease did not occur at levels <104 copies/ml.6 At the NIH viral loads >104 copies/ml are rarely observed in haematopoietic stem cell transplantation patients (unpublished data) and treatment is initiated at a viral load ⩾103 copies/ml of whole blood. Guidelines for initiation of therapy at the NIH are, therefore, approximately one log different from those at the Washington University. At the NIH, in the absence of signs and symptoms of disease, treatment of patients with results between 250 and 1000 copies/ml is delayed until a result of ⩾250 is confirmed on the next test. Treatment for patients with an initial result ⩾103 copies/ml is initiated without delay. Using these guidelines, a 10% rate of CMV disease was observed at the NIH (unpublished data). This rate is similar to that observed in other studies3, 5 and at the Washington University.6

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Authors and Affiliations

  1. Department of Laboratory Medicine, Warren Grant Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    S M Harrington, L Li, S H Fischer & P R Murray

  2. Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA

    R S Buller & G A Storch

  3. Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    J C Gea-Banacloche

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  1. S M Harrington
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  2. R S Buller
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  3. G A Storch
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  4. L Li
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  7. J C Gea-Banacloche
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Correspondence to S M Harrington.

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Harrington, S., Buller, R., Storch, G. et al. The effect of quantification standards used in real-time CMV PCR assays on guidelines for initiation of therapy in allogeneic stem cell transplant patients. Bone Marrow Transplant 39, 237–238 (2007). https://doi.org/10.1038/sj.bmt.1705558

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