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08.04.2018 | Original Article | Ausgabe 8/2018

Annals of Hematology 8/2018

Significance of circulating Epstein-Barr virus DNA monitoring after remission in patients with extranodal natural killer T cell lymphoma

Zeitschrift:
Annals of Hematology > Ausgabe 8/2018
Autoren:
Jinhyun Cho, Seok Jin Kim, Silvia Park, Kwai Han Yoo, Chang-Seok Ki, Younghyeh Ko, Won Seog Kim
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00277-018-3313-x) contains supplementary material, which is available to authorized users.

Abstract

Circulating Epstein-Barr virus (EBV)-DNA has been established as a useful parameter for diagnosis and predicting prognosis in patients with extranodal natural killer T cell lymphoma (ENKTL); however, the role of monitoring of circulating EBV-DNA after complete remission (CR) is not well established. From January 2008 to August 2016, 328 ENKTL patents were enrolled in 2 lymphoma cohorts. Of 171 patients achieved a CR, 81 had available monitoring data for circulating EBV-DNA with negative post-treatment EBV-DNA. Measurement of circulating EBV-DNA was performed from unfractionated whole blood and calculated according to WHO international standards. Median duration of follow-up was 40.4 months. In 31 of the 81 patients (38.8%), circulating EBV-DNA was detected at least once during follow-up, and 16 of these patients (51.6%) experienced relapse. In contrast, only 7 out of 50 (14.0%) patients with consistently undetectable circulating EBV-DNA experienced relapse (p < 0.001). In multivariate analysis, positive conversion of circulating EBV-DNA was the only independent prognostic factor for occurrence of relapse (HR = 6.552, p < 0.001), progression-free survival (HR = 4.549, p = 0.01), and overall survival (HR = 8.726, p < 0.001). Patients with a higher level of circulating EBV-DNA than 3310 IU/mL (3.52 log10 IU/mL) showed a strong tendency to relapse (73.3 vs. 31.3%, p = 0.019). In conclusion, positive conversion of circulating EBV-DNA was a valuable indicator of relapse and inferior survival, especially if the level was higher than 3310 IU/mL in ENKTL patients had achieved CR. Close follow-up is necessary for patients developed detectable circulating EBV-DNA after remission.

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Zusatzmaterial
Supplementary Fig. 1 Determination of cut-off value using receiver operating characteristics (ROC) curve. ROC curve is a useful method to evaluate the performance of a diagnostic test with classification of subjects into two categories of positive and negative. In a ROC curve the sensitivity (true positive rate) is plotted as a function of the false positive rate (1-specificity) for different cut-off points. Each point on the ROC curve represents a sensitivity/specificity pair corresponding to a particular decision threshold. The closer the ROC curve is to the upper left corner, the higher the overall accuracy of the test. (JPEG 37 kb)
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Supplementary Fig. 2 Changes in EBV-DNA viral load in blood from the time of completing treatment to the time of relapse or last follow-up in patients with positive conversion of circulating EBV-DNA (N = 31). (a) Serial changes in circulating EBV-DNA level in patients with relapse (N = 16). Graphs show a trend toward increasing level of circulating EBV-DNA more than 3310 IU/ml (3.52 log10 IU/mL) at the time of relapse or before relapse. (b) Serial changes in circulating EBV-DNA level in patients without relapse (N = 15). Levels of circulating EBV-DNA were relatively low in most patients. (JPEG 167 kb)
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High resolution image (TIFF 232 kb)
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