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Published in: International Journal of Hematology 3/2015

01-09-2015 | Case Report

Reactivation of resolved infection with the hepatitis B virus immune escape mutant G145R during dasatinib treatment for chronic myeloid leukemia

Authors: Toshihiko Ando, Kensuke Kojima, Hiroshi Isoda, Yuichiro Eguchi, Takashi Honda, Masatoshi Ishigami, Shinya Kimura

Published in: International Journal of Hematology | Issue 3/2015

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Abstract

Reactivation of hepatitis B virus (HBV) following immunosuppressive therapy or hematopoietic stem cell transplantation is a potentially fatal complication that may occur even in patients with prior resolution of HBV infection. Dasatinib is a small-molecule inhibitor of the tyrosine kinases SRC and ABL that has been approved for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. Here, we report the first case of reactivation of resolved infection with the HBV immune escape mutant G145R in a CML patient receiving dasatinib. Although dasatinib is not recognized as an immunosuppressant, our observations suggest that dasatinib may enhance HBV replication and induce its reactivation in immunocompetent patients, that HBV escape mutants may contribute to the pathogenesis of HBV reactivation, and that close monitoring of HBV status is advisable in patients with current or resolved HBV infection.
Literature
1.
2.
go back to reference Fukushima N, Mizuta T, Tanaka M, Yokoo M, Ide M, Hisatomi T, et al. Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier. Ann Oncol. 2009;20:2013–7.CrossRefPubMed Fukushima N, Mizuta T, Tanaka M, Yokoo M, Ide M, Hisatomi T, et al. Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier. Ann Oncol. 2009;20:2013–7.CrossRefPubMed
3.
go back to reference Skrabs C, Müller C, Agis H, Mannhalter C, Jäger U. Treatment of HBV-carrying lymphoma patients with Rituximab and CHOP: a diagnostic and therapeutic challenge. Leukemia. 2002;16:1884–6.CrossRefPubMed Skrabs C, Müller C, Agis H, Mannhalter C, Jäger U. Treatment of HBV-carrying lymphoma patients with Rituximab and CHOP: a diagnostic and therapeutic challenge. Leukemia. 2002;16:1884–6.CrossRefPubMed
4.
go back to reference Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11.CrossRefPubMed Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11.CrossRefPubMed
5.
go back to reference Coppola N, Tonziello G, Pisaturo M, Messina V, Guastafierro S, Fiore M, et al. Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings. J Med Virol. 2011;83:1909–16.CrossRefPubMed Coppola N, Tonziello G, Pisaturo M, Messina V, Guastafierro S, Fiore M, et al. Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings. J Med Virol. 2011;83:1909–16.CrossRefPubMed
6.
go back to reference Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients’ recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med. 1996;2:1104–8.CrossRefPubMed Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients’ recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med. 1996;2:1104–8.CrossRefPubMed
7.
go back to reference Oketani M, Ido A, Uto H, Tsubouchi H. Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatol Res. 2012;42:627–36.CrossRefPubMed Oketani M, Ido A, Uto H, Tsubouchi H. Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatol Res. 2012;42:627–36.CrossRefPubMed
8.
go back to reference Umemura T, Tanaka E, Kiyosawa K, Kumada H, Japan de novo Hepatitis B Research Group. Mortality secondary to fulminant hepatic failure in patients with prior resolution of hepatitis B virus infection in Japan. Clin Infect Dis. 2008;47:e52–6.CrossRefPubMed Umemura T, Tanaka E, Kiyosawa K, Kumada H, Japan de novo Hepatitis B Research Group. Mortality secondary to fulminant hepatic failure in patients with prior resolution of hepatitis B virus infection in Japan. Clin Infect Dis. 2008;47:e52–6.CrossRefPubMed
9.
go back to reference Fujisawa S, Nakamae H, Ogura M, Ishizawa K, Taniwaki M, Utsunomiya A, et al. Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): subset analysis of the DASISION trial with 2-year follow-up. Int J Hematol. 2014;99:141–53.CrossRefPubMed Fujisawa S, Nakamae H, Ogura M, Ishizawa K, Taniwaki M, Utsunomiya A, et al. Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): subset analysis of the DASISION trial with 2-year follow-up. Int J Hematol. 2014;99:141–53.CrossRefPubMed
10.
go back to reference Kimura S, Ando T, Kojima K. Ever-advancing chronic myeloid leukemia treatment. Int J Clin Oncol. 2014;19:3–9.CrossRefPubMed Kimura S, Ando T, Kojima K. Ever-advancing chronic myeloid leukemia treatment. Int J Clin Oncol. 2014;19:3–9.CrossRefPubMed
11.
go back to reference Aoe M, Shimada A, Muraoka M, Washio K, Nakamura Y, Takahashi T, et al. ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases. Int J Hematol. 2014;99:609–15.CrossRefPubMed Aoe M, Shimada A, Muraoka M, Washio K, Nakamura Y, Takahashi T, et al. ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases. Int J Hematol. 2014;99:609–15.CrossRefPubMed
12.
go back to reference Wölfl M, Langhammer F, Wiegering V, Eyrich M, Schlegel PG. Dasatinib medication causing profound immunosuppression in a patient after haploidentical SCT: functional assays from whole blood as diagnostic clues. Bone Marrow Transplant. 2013;48:875–7.CrossRefPubMed Wölfl M, Langhammer F, Wiegering V, Eyrich M, Schlegel PG. Dasatinib medication causing profound immunosuppression in a patient after haploidentical SCT: functional assays from whole blood as diagnostic clues. Bone Marrow Transplant. 2013;48:875–7.CrossRefPubMed
13.
go back to reference Sillaber C, Herrmann H, Bennett K, Rix U, Baumgartner C, Böhm A, et al. Immunosuppression and atypical infections in CML patients treated with dasatinib at 140 mg daily. Eur J Clin Invest. 2009;39:1098–109.CrossRefPubMed Sillaber C, Herrmann H, Bennett K, Rix U, Baumgartner C, Böhm A, et al. Immunosuppression and atypical infections in CML patients treated with dasatinib at 140 mg daily. Eur J Clin Invest. 2009;39:1098–109.CrossRefPubMed
14.
go back to reference Kreutzman A, Ladell K, Koechel C, Gostick E, Ekblom M, Stenke L, et al. Expansion of highly differentiated CD8 + T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation. Leukemia. 2011;25:1587–97.CrossRefPubMed Kreutzman A, Ladell K, Koechel C, Gostick E, Ekblom M, Stenke L, et al. Expansion of highly differentiated CD8 + T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation. Leukemia. 2011;25:1587–97.CrossRefPubMed
15.
go back to reference Mustjoki S, Auvinen K, Kreutzman A, Rousselot P, Hernesniemi S, Melo T, et al. Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy. Leukemia. 2013;27:914–24.CrossRefPubMed Mustjoki S, Auvinen K, Kreutzman A, Rousselot P, Hernesniemi S, Melo T, et al. Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy. Leukemia. 2013;27:914–24.CrossRefPubMed
16.
go back to reference Kim DH, Kamel-Reid S, Chang H, Sutherland R, Jung CW, Kim HJ, et al. Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica. 2009;94:135–9.PubMedCentralCrossRefPubMed Kim DH, Kamel-Reid S, Chang H, Sutherland R, Jung CW, Kim HJ, et al. Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica. 2009;94:135–9.PubMedCentralCrossRefPubMed
17.
go back to reference Ikeda K, Shiga Y, Takahashi A, Kai T, Kimura H, Takeyama K, et al. Fatal hepatitis B virus reactivation in a chronic myeloid leukemia patient during imatinib mesylate treatment. Leuk Lymphoma. 2006;47:155–7.CrossRefPubMed Ikeda K, Shiga Y, Takahashi A, Kai T, Kimura H, Takeyama K, et al. Fatal hepatitis B virus reactivation in a chronic myeloid leukemia patient during imatinib mesylate treatment. Leuk Lymphoma. 2006;47:155–7.CrossRefPubMed
18.
go back to reference Kang BW, Lee SJ, Moon JH, Kim SN, Chae YS, Kim JG, et al. Chronic myeloid leukemia patient manifesting fatal hepatitis B virus reactivation during treatment with imatinib rescued by liver transplantation: case report and literature review. Int J Hematol. 2009;90:383–7.CrossRefPubMed Kang BW, Lee SJ, Moon JH, Kim SN, Chae YS, Kim JG, et al. Chronic myeloid leukemia patient manifesting fatal hepatitis B virus reactivation during treatment with imatinib rescued by liver transplantation: case report and literature review. Int J Hematol. 2009;90:383–7.CrossRefPubMed
19.
go back to reference Lai GM, Yan SL, Chang CS, Tsai CY. Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor. World J Gastroenterol. 2013;19:1318–21.PubMedCentralCrossRefPubMed Lai GM, Yan SL, Chang CS, Tsai CY. Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor. World J Gastroenterol. 2013;19:1318–21.PubMedCentralCrossRefPubMed
20.
go back to reference Seggewiss R, Loré K, Greiner E, Magnusson MK, Price DA, Douek DC, Dunbar CE, Wiestner A. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood. 2005;105:2473–9.CrossRefPubMed Seggewiss R, Loré K, Greiner E, Magnusson MK, Price DA, Douek DC, Dunbar CE, Wiestner A. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood. 2005;105:2473–9.CrossRefPubMed
21.
go back to reference Cwynarski K, Laylor R, Macchiarulo E, Goldman J, Lombardi G, Melo JV, Dazzi F. Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Leukemia. 2004;18:1332–9.CrossRefPubMed Cwynarski K, Laylor R, Macchiarulo E, Goldman J, Lombardi G, Melo JV, Dazzi F. Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Leukemia. 2004;18:1332–9.CrossRefPubMed
22.
go back to reference Chen J, Schmitt A, Chen B, Rojewski M, Rübeler V, Fei F, et al. Nilotinib hampers the proliferation and function of CD8 + T lymphocytes through inhibition of T cell receptor signalling. J Cell Mol Med. 2008;12:2107–18.PubMedCentralCrossRefPubMed Chen J, Schmitt A, Chen B, Rojewski M, Rübeler V, Fei F, et al. Nilotinib hampers the proliferation and function of CD8 + T lymphocytes through inhibition of T cell receptor signalling. J Cell Mol Med. 2008;12:2107–18.PubMedCentralCrossRefPubMed
23.
go back to reference Liaw YF. Hepatitis viruses under immunosuppressive agents. J Gastroenterol Hepatol. 1998;13:14–20.CrossRefPubMed Liaw YF. Hepatitis viruses under immunosuppressive agents. J Gastroenterol Hepatol. 1998;13:14–20.CrossRefPubMed
24.
go back to reference Sheldon J, Soriano V. Hepatitis B virus escape mutants induced by antiviral therapy. J Antimicrob Chemother. 2008;61:766–8.CrossRefPubMed Sheldon J, Soriano V. Hepatitis B virus escape mutants induced by antiviral therapy. J Antimicrob Chemother. 2008;61:766–8.CrossRefPubMed
25.
go back to reference Locarnini SA, Yuen L. Molecular genesis of drug-resistant and vaccine-escape HBV mutants. Antivir Ther. 2010;15:451–61.CrossRefPubMed Locarnini SA, Yuen L. Molecular genesis of drug-resistant and vaccine-escape HBV mutants. Antivir Ther. 2010;15:451–61.CrossRefPubMed
26.
go back to reference Ishigami M, Honda T, Ishizu Y, Onishi Y, Kamei H, Hayashi K, et al. Frequent incidence of escape mutants after successful hepatitis B vaccine response and stopping of nucleos(t)ide analogues in liver transplant recipients. Liver Transpl. 2014;20:1211–20.CrossRefPubMed Ishigami M, Honda T, Ishizu Y, Onishi Y, Kamei H, Hayashi K, et al. Frequent incidence of escape mutants after successful hepatitis B vaccine response and stopping of nucleos(t)ide analogues in liver transplant recipients. Liver Transpl. 2014;20:1211–20.CrossRefPubMed
27.
go back to reference Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, et al. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood. 2003;102:1930.CrossRefPubMed Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, et al. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood. 2003;102:1930.CrossRefPubMed
28.
go back to reference Kamitsukasa H, Iri M, Tanaka A, Nagashima S, Takahashi M, Nishizawa T, et al. Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection. J Med Virol. 2015;87:589–600.CrossRefPubMed Kamitsukasa H, Iri M, Tanaka A, Nagashima S, Takahashi M, Nishizawa T, et al. Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection. J Med Virol. 2015;87:589–600.CrossRefPubMed
Metadata
Title
Reactivation of resolved infection with the hepatitis B virus immune escape mutant G145R during dasatinib treatment for chronic myeloid leukemia
Authors
Toshihiko Ando
Kensuke Kojima
Hiroshi Isoda
Yuichiro Eguchi
Takashi Honda
Masatoshi Ishigami
Shinya Kimura
Publication date
01-09-2015
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 3/2015
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-015-1788-y

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