The Value of Tissue Polymerase Chain Reaction Testing for the Diagnosis of Tissue-Invasive Cytomegalovirus Disease Following Allogeneic Hematopoietic Cell Transplantation

Background: CMV disease is a major complication of allogeneic hematopoietic cell transplantation (HCT). Our widely used diagnostic modalities (HE Figure 1). Using this cutoff, 45% of equivocal cases were classified as negative, suggesting that anti-CMV treatment in almost half of Hu0026E/IHC-equivocal cases is unnecessary and potentially detrimental. Among viremic, Hu0026E/IHC-concordant cases, tissue PCR with a cutoff Ct of 40 had a sensitivity of 100%, specificity of 50%, PPV of 44%, and NPV of 100%. Among non-viremic, Hu0026E/IHC-concordant cases, these numbers were 80%, 91%, 36%, and 99%, respectively. In this analysis on viremic cases, all double-positive and 50% of double-negative cases were classified positive, while 31% of equivocal cases were classified negative. In non-viremic patients, 91% of double-negatives, 20% of double-positives, and 62% of equivocal cases were classified negative. Conclusions: Tissue PCR is a useful adjunct to Hu0026E and IHC, particularly in Hu0026E/IHC-equivocal cases, and can help avoid unnecessary, potentially toxic, anti-CMV treatment in cases without tissue-invasive disease. We propose the following algorithm: ( i ) If the cost and labor associated with tissue PCR on all patients are prohibitive, start with Hu0026E and IHC. Perform tissue PCR in Hu0026E/IHC-equivocal cases and consider this test also in non-viremic, Hu0026E/IHC-positive cases. In all other cases forgo tissue PCR. ( ii ) If the cost and labor are not prohibitive, perform PCR on all cases. A negative PCR rules out CMV disease. In PCR-positive cases, use Hu0026E/IHC results and treat only if Hu0026E and IHC are both positive. One limitation of our study is related to using FFPE specimens rather than the real-life fresh tissue. Our results warrant testing in prospective studies. Disclosures DiPersio: Incyte Corporation: Research Funding.