Risk factor and mechanism of reactivation of hepatitis B virus following systemic chemotherapy

• Project/Area Number: 24591428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya City University
• Principal Investigator: KUSUMOTO Shigeru 名古屋市立大学, 医学(系)研究科(研究院), 講師 (90423855)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Yasuhito 名古屋市立大学, 大学院医学研究科, 教授 (90336694)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: B型肝炎ウイルス再活性化 / HBV再活性化 / がん分子標的治療 / B型肝炎 / がん化学療法 / HBV DNAモニタリング / 再活性化

Outline of Final Research Achievements

Reactivation of hepatitis B virus is a potentially fatal complication following systemic chemotherapy. HBV reactivation may occur not only in patients with seropositive for HBsAg, but also in patients with seropositive for anti-HBc and/or anti-HBs (HBV resolved infection). This study demonstrated that if a potentially immune-enhancing drug is used for HBsAg-positive cancer patients with high HBV DNA levels, HBV reactivation-related death may occur despite antiviral prophylaxis before hepatitis onset. This study also showed that HBV reactivation may occur not only in patients with B-cell lymphoma who received rituximab-containing chemotherapy, but also with T-cell lymphoma. In near future, new molecular target drugs may change the risk of HBV reactivation.

Research Products

• [Journal Article] Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-cell Lymphoma: A prospective observational study. (2015)
  • Author(s): Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Takasaki H, et al.
  • Journal Title: Clin Infect Dis. Volume: in press
  • Peer Reviewed
• [Journal Article] Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma. (2015)
  • Author(s): Masaki A, Ishida T, Maeda Y, Suzuki S, Ito A, Takino H, Ogura H, Totani H, Yoshida T, Kinoshita S, Narita T, Ri M, Kusumoto S, Inagaki A, Komatsu H, Niimi A, Ueda R, Utsunomiya A, Inagaki H, Iida S.
  • Journal Title: Clin Cancer Res. Volume: in press
  • NAID: 130005130183
  • Peer Reviewed
• [Journal Article] Fatal reactivation of hepatitis B virus infection in a patient with adult T-cell leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab. (2015)
  • Author(s): Ifuku H, Kusumoto S, Tanaka Y, Totani H, Ishida T, Okada M, Murakami S, Mizokami M, Ueda R, Iida S.
  • Journal Title: Hepatol Res. Volume: in press Issue: 13 Pages: 1363-1367
  • DOI: 10.1111/hepr.12513
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phase I study of pegylated liposomal doxorubicin in combination with bortezomib for Japanese patients with relapsed or refractory multiple myeloma. (2015)
  • Author(s): Kusumoto S, Sunami K, Inagaki M, Iida S.
  • Journal Title: Int J Hematol. Volume: in press
  • NAID: 40020854756
  • Peer Reviewed
• [Journal Article] Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy (2015)
  • Author(s): Totani H, Kusumoto S, Ishida T, Masuda A, Yoshida T, Ito A, Ri M, Komatsu H, Murakami S, Mizokami M, Ueda R, Niimi A, Inagaki H, Tanaka Y, Iida S.
  • Journal Title: International Journal of Hematology Volume: 印刷中 Issue: 4 Pages: 398-404
  • DOI: 10.1007/s12185-015-1750-z
  • Peer Reviewed
• [Journal Article] Multicenter cooperative case survey of Hepatitis B virus reactivation by chemotherapeutic agents. (2015)
  • Author(s): Takahashi H, Ikeda M, Kumada T, Osaki Y, Kondo S, Kusumoto S, Ohkawa K, Nadano S, Furuse J, Kudo M, Ito K, Yokoyama M, Okusaka T, Shimoyama M, Mizokami M
  • Journal Title: Hepatol Res Volume: Jan 27 Issue: 12 Pages: 1220-1227
  • DOI: 10.1111/hepr.12496
  • Peer Reviewed
• [Journal Article] CD30-positive primary bone marrow lymphoma mimicking Hodgkin lymphoma (2015)
  • Author(s): Suzuki T, Kusumoto S, Masaki A, Ishida T, Inagaki H, Iida S, Mori F.
  • Journal Title: International Journal of Hematology Volume: 印刷中 Issue: 2 Pages: 109-11
  • DOI: 10.1007/s12185-014-1714-8
  • Peer Reviewed
• [Journal Article] Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy. (2014)
  • Author(s): Kusumoto S, Tobinai K.
  • Journal Title: Hematology Am Soc Hematol Educ Program. Volume: 1 Issue: 1 Pages: 576-83
  • DOI: 10.1182/asheducation-2014.1.576
  • Peer Reviewed
• [Journal Article] Amelanotic malignant melanoma of unknown primary origin metastasizing to the bone marrow: a case report and review of the literature. (2014)
  • Author(s): Suzuki T, Kusumoto S, Iida S, Tada T, Mori F.
  • Journal Title: Intern Med. Volume: 53 Pages: 325-328
  • NAID: 130003392650
  • Peer Reviewed
• [Journal Article] HTLV-1 bZIP factor-specific CD4 T cell responses in adult T cell leukemia/lymphoma patients after allogeneic hematopoietic stem cell transplantation. (2014)
  • Author(s): Narita T, Ishida T, Masaki A, Suzuki S, Ito A, Mori F, Yamada T, Ri M, Kusumoto S, Komatsu H, Miyazaki Y, Takatsuka Y, Utsunomiya A, Niimi A, Iida S, Ueda R.
  • Journal Title: J Immunol. Volume: 192 Issue: 3 Pages: 940-947
  • DOI: 10.4049/jimmunol.1301952
  • Peer Reviewed
• [Journal Article] Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model (2014)
  • Author(s): Mori F, Ishida T, Ito A, Sato F, Masaki A, Narita T, Suzuki S, Yamada T, Takino H, Ri M, Kusumoto S, Komatsu H, Hishizawa M, Imada K, Takaori-Kondo A, Niimi A, Ueda R, Inagaki H, Iida S
  • Journal Title: European Journal of Haematology Volume: 92 Issue: 3 Pages: 219-228
  • DOI: 10.1111/ejh.12231
  • Peer Reviewed
• [Journal Article] Reactivation of hepatitis B virus in a patient with adult T-cell leukemia/lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab. (2013)
  • Author(s): Nakano N
  • Journal Title: Hepatol Res. Volume: Epub ahead Issue: 3 Pages: 354-357
  • DOI: 10.1111/hepr.12117
  • Peer Reviewed
• [Journal Article] Is antiviral prophylaxis necessary to prevent hepatitis B virus (HBV) reactivation in patients with HBV-resolved infection receiving rituximab-containing chemotherapy? (2013)
  • Author(s): Kusumoto S, Tanaka Y, Mizokami M, Ueda R.
  • Journal Title: J Clin Oncol. Volume: 31 Issue: 35 Pages: 4480-4480
  • DOI: 10.1200/jco.2013.52.1278
• [Journal Article] Strategy for preventing hepatitis B reactivation in patients with resolved HBV infection following rituximab-containing chemotherapy. (2013)
  • Author(s): Kusumoto S, Tanaka Y, Mizokami M, Ueda R.
  • Journal Title: Hepatology. Volume: in press Issue: 2 Pages: 765-766
  • DOI: 10.1002/hep.26963
• [Journal Article] Successful salvage therapy using lenalidomide in a patient with relapsed multiple myeloma after allogeneic hematopoietic stem cell transplantation. (2013)
  • Author(s): Suzuki T, Kusumoto S, Yoshida T, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Niimi A, Iida S.
  • Journal Title: Int J Hematol Volume: in press Issue: 4 Pages: 540-543
  • DOI: 10.1007/s12185-013-1301-4
  • NAID: 10031168524
  • Peer Reviewed
• [Journal Article] Stevens-Johnson Syndrome associated with mogamulizumab treatment of adult T-cell leukemia / lymphoma. (2013)
  • Author(s): Ishida T
  • Journal Title: Cancer Sci. Volume: 104 Issue: 5 Pages: 647-50
  • DOI: 10.1111/cas.12116
  • Peer Reviewed
• [Journal Article] Angioimmunoblastic T-cell lymphoma mice model. (2013)
  • Author(s): Sato F
  • Journal Title: Leuk Res. Volume: 37 Issue: 1 Pages: 21-7
  • DOI: 10.1016/j.leukres.2012.09.009
  • Peer Reviewed
• [Journal Article] Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma. (2012)
  • Author(s): Suzuki S, Masaki A, Ishida T, Ito A, Mori F, Sato F, Narita T, Ri M, Kusumoto S, Komatsu H, Fukumori Y, Nishikawa H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R.
  • Journal Title: Cancer Sci. Volume: 103 Pages: 1764-1773
  • Peer Reviewed
• [Presentation] がん分子標的治療中のB型肝炎ウイルス再活性化のリスクとその対策 (2014)
  • Author(s): 楠本茂
  • Organizer: 第76回 日本血液学会学術集会 コーポレートセミナー36
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-11-02
  • Invited
• [Presentation] B型肝炎ウイルス(HBV)既往感染を有する 成人T細胞白血病/リンパ腫患者におけるHBV再活性化の後方視的研究 (2014)
  • Author(s): 戸谷 治仁、楠本茂、石田高司、伊藤旭、李政樹、小松弘和、上田龍三、田中靖人、新実 彰男、飯田真介
  • Organizer: 第12回日本臨床腫瘍学会学術集会O2-7-3
  • Place of Presentation: 福岡国際会議場（福岡県）
  • Year and Date: 2014-07-18
• [Presentation] がん化学療法中のB型肝炎ウイルス再活性化のリスクとその対策：最新エビデンスより (2014)
  • Author(s): 楠本茂
  • Organizer: 第50回日本肝臓学会総会イブニングセミナー
  • Place of Presentation: ホテルニューオータニ （東京都）
  • Year and Date: 2014-05-29
  • Invited
• [Presentation] リツキシマブ＋ステロイド併用悪性リンパ腫治療中のde novo B型肝炎対策：HBV DNA モニタリングによるpreemptive antiviral therapyの有用性の検討 (2013)
  • Author(s): 楠本茂, 田中靖人, 溝上雅史
  • Organizer: JDDW2013、シンポジウム S1 ：B型肝炎ウイルス再活性化の予防・治療の現状と課題
  • Place of Presentation: グランドプリンスホテル新高輪 (東京)
• [Presentation] 血液疾患治療中のHBV再活性化対策に関する最新エビデンス (2013)
  • Author(s): 楠本茂
  • Organizer: 第75回日本血液学会学術集会、コーポレートセミナー8
  • Place of Presentation: ロイトン札幌 (札幌)
• [Presentation] Prospective Nationwide Observational Study of Hepatitis B Virus (HBV) DNA Monitoring and Preemptive Antiviral Therapy for HBV Reactivation in Patients with B-Cell Non-Hodgkin Lymphoma Following Rituximab Containing Chemotherapy: Results of Interim Analysis (2012)
  • Author(s): Kusumoto S, Tanaka Y, Suzuki R, et al.
  • Organizer: 54th American Society of Hematology Annual Meeting
  • Place of Presentation: Georgia World Congress Center (Atlanta, USA)