Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: A Japanese multicenter analysis

Daisuke Ennishi, Yoshinobu Maeda, Nozomi Niitsu, Minoru Kojima, Koji Izutsu, Jun Takizawa, Shigeru Kusumoto, Masataka Okamoto, Masahiro Yokoyama, Yasushi Takamatsu, Kazutaka Sunami, Akira Miyata, Kayoko Murayama, Akira Sakai, Morio Matsumoto, Katsuji Shinagawa, Akinobu Takaki, Keitaro Matsuo, Tomohiro Kinoshita, Mitsune Tanimoto

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Abstract

The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P <.001). An exploratory analysis revealed that pre-treatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients.

Original languageEnglish
Pages (from-to)5119-5125
Number of pages7
JournalBlood
Volume116
Issue number24
DOIs
Publication statusPublished - Dec 9 2010

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Chemotherapy
Lymphoma, Large B-Cell, Diffuse
Viruses
Hepacivirus
Toxicity
Cells
Drug Therapy
Liver
Virus Diseases
Rituximab
Survival
Vincristine
Prednisone
Transaminases
Viral Load
Doxorubicin
Cyclophosphamide
Disease-Free Survival
Hazards
Multivariate Analysis

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens : A Japanese multicenter analysis. / Ennishi, Daisuke; Maeda, Yoshinobu; Niitsu, Nozomi; Kojima, Minoru; Izutsu, Koji; Takizawa, Jun; Kusumoto, Shigeru; Okamoto, Masataka; Yokoyama, Masahiro; Takamatsu, Yasushi; Sunami, Kazutaka; Miyata, Akira; Murayama, Kayoko; Sakai, Akira; Matsumoto, Morio; Shinagawa, Katsuji; Takaki, Akinobu; Matsuo, Keitaro; Kinoshita, Tomohiro; Tanimoto, Mitsune.

In: Blood, Vol. 116, No. 24, 09.12.2010, p. 5119-5125.

Research output: Contribution to journalArticle

Ennishi, D, Maeda, Y, Niitsu, N, Kojima, M, Izutsu, K, Takizawa, J, Kusumoto, S, Okamoto, M, Yokoyama, M, Takamatsu, Y, Sunami, K, Miyata, A, Murayama, K, Sakai, A, Matsumoto, M, Shinagawa, K, Takaki, A, Matsuo, K, Kinoshita, T & Tanimoto, M 2010, 'Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: A Japanese multicenter analysis', Blood, vol. 116, no. 24, pp. 5119-5125. https://doi.org/10.1182/blood-2010-06-289231
Ennishi, Daisuke ; Maeda, Yoshinobu ; Niitsu, Nozomi ; Kojima, Minoru ; Izutsu, Koji ; Takizawa, Jun ; Kusumoto, Shigeru ; Okamoto, Masataka ; Yokoyama, Masahiro ; Takamatsu, Yasushi ; Sunami, Kazutaka ; Miyata, Akira ; Murayama, Kayoko ; Sakai, Akira ; Matsumoto, Morio ; Shinagawa, Katsuji ; Takaki, Akinobu ; Matsuo, Keitaro ; Kinoshita, Tomohiro ; Tanimoto, Mitsune. / Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens : A Japanese multicenter analysis. In: Blood. 2010 ; Vol. 116, No. 24. pp. 5119-5125.
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T1 - Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens

T2 - A Japanese multicenter analysis

AU - Ennishi, Daisuke

AU - Maeda, Yoshinobu

AU - Niitsu, Nozomi

AU - Kojima, Minoru

AU - Izutsu, Koji

AU - Takizawa, Jun

AU - Kusumoto, Shigeru

AU - Okamoto, Masataka

AU - Yokoyama, Masahiro

AU - Takamatsu, Yasushi

AU - Sunami, Kazutaka

AU - Miyata, Akira

AU - Murayama, Kayoko

AU - Sakai, Akira

AU - Matsumoto, Morio

AU - Shinagawa, Katsuji

AU - Takaki, Akinobu

AU - Matsuo, Keitaro

AU - Kinoshita, Tomohiro

AU - Tanimoto, Mitsune

PY - 2010/12/9

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N2 - The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P <.001). An exploratory analysis revealed that pre-treatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients.

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