High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for Adult T cell leukemia

Masao Ogata, Takako Satou, Rie Kawano, Tetsushi Yoshikawa, Junji Ikewaki, Kazuhiro Kohno, Takeaki Ando, Yasuhiko Miyazaki, Eiichi Ohtsuka, Yoshio Saburi, Hiroshi Kikuchi, Tetsunori Saikawa, Jun ichi Kadota

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Abstract

The etiology of cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and Epstein-Barr virus (EBV) reactivation and the potential for complications following cytotoxic chemotherapy in the absence of allogeneic transplantation are not clearly understood. Patients with adult T cell leukemia (ATL) are susceptible to opportunistic infections. In this study, the incidence, kinetics and clinical significance of reactivation of CMV, HHV-6, and EBV in ATL patients were investigated. Viral DNA in a total of 468 plasma samples from 34 patients was quantified using real-time PCR. The probability of CMV, HHV-6, and EBV reactivation by 100 days after the start of chemotherapy was 50.6%, 52.3%, and 21.6%, respectively. Although most CMV reactivations were self-limited, plasma CMV DNA tended to persist or increase if the CMV DNA levels in plasma reached ≥104copies/ml. CMV reactivation was negatively associated with survival, but the P-value for this association was near the borderline of statistical significance (P=0.052). One patient developed fatal interstitial pneumonia concomitant with peak CMV DNA accumulation (1.6×106copies/ml plasma). Most HHV-6 and EBV reactivations were self-limited, and no disease resulting from HHV-6 or EBV was confirmed. HHV-6 and EBV reactivation were not associated with reduced survival (P=0.35 and 0.11, respectively). These findings demonstrated that subclinical reactivation of CMV, HHV-6, and EBV were common in ATL patients receiving chemotherapy. There were differences in the viral reactivation patterns among the three viruses. A CMV load ≥104copies/ml plasma was indicative of subsequent exacerbation of CMV reactivation and developing serious clinical course.

Original languageEnglish
Pages (from-to)702-709
Number of pages8
JournalJournal of Medical Virology
Volume83
Issue number4
DOIs
Publication statusPublished - 01-04-2011

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Human Herpesvirus 6
Adult T Cell Leukemia Lymphoma
Cytomegalovirus
Human Herpesvirus 4
Drug Therapy
Incidence
DNA
Survival
Interstitial Lung Diseases
Homologous Transplantation
Opportunistic Infections
Viral DNA
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Ogata, Masao ; Satou, Takako ; Kawano, Rie ; Yoshikawa, Tetsushi ; Ikewaki, Junji ; Kohno, Kazuhiro ; Ando, Takeaki ; Miyazaki, Yasuhiko ; Ohtsuka, Eiichi ; Saburi, Yoshio ; Kikuchi, Hiroshi ; Saikawa, Tetsunori ; Kadota, Jun ichi. / High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for Adult T cell leukemia. In: Journal of Medical Virology. 2011 ; Vol. 83, No. 4. pp. 702-709.
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abstract = "The etiology of cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and Epstein-Barr virus (EBV) reactivation and the potential for complications following cytotoxic chemotherapy in the absence of allogeneic transplantation are not clearly understood. Patients with adult T cell leukemia (ATL) are susceptible to opportunistic infections. In this study, the incidence, kinetics and clinical significance of reactivation of CMV, HHV-6, and EBV in ATL patients were investigated. Viral DNA in a total of 468 plasma samples from 34 patients was quantified using real-time PCR. The probability of CMV, HHV-6, and EBV reactivation by 100 days after the start of chemotherapy was 50.6{\%}, 52.3{\%}, and 21.6{\%}, respectively. Although most CMV reactivations were self-limited, plasma CMV DNA tended to persist or increase if the CMV DNA levels in plasma reached ≥104copies/ml. CMV reactivation was negatively associated with survival, but the P-value for this association was near the borderline of statistical significance (P=0.052). One patient developed fatal interstitial pneumonia concomitant with peak CMV DNA accumulation (1.6×106copies/ml plasma). Most HHV-6 and EBV reactivations were self-limited, and no disease resulting from HHV-6 or EBV was confirmed. HHV-6 and EBV reactivation were not associated with reduced survival (P=0.35 and 0.11, respectively). These findings demonstrated that subclinical reactivation of CMV, HHV-6, and EBV were common in ATL patients receiving chemotherapy. There were differences in the viral reactivation patterns among the three viruses. A CMV load ≥104copies/ml plasma was indicative of subsequent exacerbation of CMV reactivation and developing serious clinical course.",
author = "Masao Ogata and Takako Satou and Rie Kawano and Tetsushi Yoshikawa and Junji Ikewaki and Kazuhiro Kohno and Takeaki Ando and Yasuhiko Miyazaki and Eiichi Ohtsuka and Yoshio Saburi and Hiroshi Kikuchi and Tetsunori Saikawa and Kadota, {Jun ichi}",
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Ogata, M, Satou, T, Kawano, R, Yoshikawa, T, Ikewaki, J, Kohno, K, Ando, T, Miyazaki, Y, Ohtsuka, E, Saburi, Y, Kikuchi, H, Saikawa, T & Kadota, JI 2011, 'High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for Adult T cell leukemia', Journal of Medical Virology, vol. 83, no. 4, pp. 702-709. https://doi.org/10.1002/jmv.22013

High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for Adult T cell leukemia. / Ogata, Masao; Satou, Takako; Kawano, Rie; Yoshikawa, Tetsushi; Ikewaki, Junji; Kohno, Kazuhiro; Ando, Takeaki; Miyazaki, Yasuhiko; Ohtsuka, Eiichi; Saburi, Yoshio; Kikuchi, Hiroshi; Saikawa, Tetsunori; Kadota, Jun ichi.

In: Journal of Medical Virology, Vol. 83, No. 4, 01.04.2011, p. 702-709.

Research output: Contribution to journalArticle

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T1 - High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for Adult T cell leukemia

AU - Ogata, Masao

AU - Satou, Takako

AU - Kawano, Rie

AU - Yoshikawa, Tetsushi

AU - Ikewaki, Junji

AU - Kohno, Kazuhiro

AU - Ando, Takeaki

AU - Miyazaki, Yasuhiko

AU - Ohtsuka, Eiichi

AU - Saburi, Yoshio

AU - Kikuchi, Hiroshi

AU - Saikawa, Tetsunori

AU - Kadota, Jun ichi

PY - 2011/4/1

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N2 - The etiology of cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and Epstein-Barr virus (EBV) reactivation and the potential for complications following cytotoxic chemotherapy in the absence of allogeneic transplantation are not clearly understood. Patients with adult T cell leukemia (ATL) are susceptible to opportunistic infections. In this study, the incidence, kinetics and clinical significance of reactivation of CMV, HHV-6, and EBV in ATL patients were investigated. Viral DNA in a total of 468 plasma samples from 34 patients was quantified using real-time PCR. The probability of CMV, HHV-6, and EBV reactivation by 100 days after the start of chemotherapy was 50.6%, 52.3%, and 21.6%, respectively. Although most CMV reactivations were self-limited, plasma CMV DNA tended to persist or increase if the CMV DNA levels in plasma reached ≥104copies/ml. CMV reactivation was negatively associated with survival, but the P-value for this association was near the borderline of statistical significance (P=0.052). One patient developed fatal interstitial pneumonia concomitant with peak CMV DNA accumulation (1.6×106copies/ml plasma). Most HHV-6 and EBV reactivations were self-limited, and no disease resulting from HHV-6 or EBV was confirmed. HHV-6 and EBV reactivation were not associated with reduced survival (P=0.35 and 0.11, respectively). These findings demonstrated that subclinical reactivation of CMV, HHV-6, and EBV were common in ATL patients receiving chemotherapy. There were differences in the viral reactivation patterns among the three viruses. A CMV load ≥104copies/ml plasma was indicative of subsequent exacerbation of CMV reactivation and developing serious clinical course.

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