Skip to main content

Advertisement

SpringerLink
Log in

Treatment with dasatinib for chronic myeloid leukemia following imatinib-induced hepatotoxicity

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Treatment with the tyrosine kinase inhibitor (TKI) imatinib for chronic myeloid leukemia in chronic phase (CML-CP) of disease may cause severe hepatotoxicity in rare cases. However, it remains unclear (1) how imatinib-induced hepatotoxicity should be treated; and (2) if and how TKI treatment can be resumed after recovery. We report a 32-year-old woman with CML-CP and histology confirmed imatinib-induced liver toxicity after 6 months of treatment. In this case, the early administration of corticosteroid therapy resulted in rapid and complete hepatic recovery, and treatment for CML-CP with the second generation TKI dasatinib was continued safely after recovery. Thus, dasatinib represents an option for maintaining therapeutic response in patients in whom continuation of imatinib is not possible due to its hepatic toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2012 update on diagnosis, monitoring, and management. Am J Hematol. 2012;87:1037–45.

    Article  CAS  PubMed  Google Scholar 

  2. Quintas-Cardama A, Kantarjian H, Jones D, Shan J, Borthakur G, Thomas D, et al. Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy. Blood. 2009;113:6315–21.

    Article  CAS  PubMed  Google Scholar 

  3. Hochhaus A, Baccarani M, Deininger M, Apperley JF, Lipton JH, Goldberg SL, et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008;22:1200–6.

    Article  CAS  PubMed  Google Scholar 

  4. Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.

    Article  CAS  PubMed  Google Scholar 

  5. Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.

    Article  CAS  PubMed  Google Scholar 

  6. Hochhaus A, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J, et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment. Blood. 2008;111:1039–43.

    Article  CAS  PubMed  Google Scholar 

  7. Kong JH, Yoo SH, Lee KE, Nam SH, Kwon JM, Lee SM, et al. Early imatinib-mesylate-induced hepatotoxicity in chronic myelogenous leukaemia. Acta Haematol. 2007;118:205–8.

    Article  CAS  PubMed  Google Scholar 

  8. Ikuta K, Torimoto Y, Jimbo J, Inamura J, Shindo M, Sato K, et al. Severe hepatic injury caused by imatinib mesylate administered for the treatment of chronic myeloid leukemia and the efficacy of prednisolone for its management. Int J Hematol. 2005;82:343–6.

    Article  PubMed  Google Scholar 

  9. Ferrero D, Pogliani EM, Rege-Cambrin G, Fava C, Mattioli G, Dellacasa C, et al. Corticosteroids can reverse severe imatinib-induced hepatotoxicity. Haematologica 2006;91:ECR27.

    Google Scholar 

  10. Yamazaki R, Okamoto S, Chen CK, Tada S, Saito H, Shibata R, et al. Successful management of liver injury caused by imatinib mesylate in a patient with previously untreated chronic myelogenous leukemia in the chronic phase. Leuk Lymphoma. 2006;47:1427–30.

    Article  PubMed  Google Scholar 

  11. Spataro V. Nilotinib in a patient with postnecrotic liver cirrhosis related to imatinib. J Clin Oncol. 2011;29:e50–2.

    Article  PubMed  Google Scholar 

  12. Perini GF, Santos FP, Funke V, Ruiz J, Neto BH, Hamerschlak N. Nilotinib post-liver transplantation for acute hepatic failure related to imatinib. Leuk Res. 2009;33:e234–5.

    Article  PubMed  Google Scholar 

  13. Cross TJ, Bagot C, Portmann B, Wendon J, Gillett D. Imatinib mesylate as a cause of acute liver failure. Am J Hematol. 2006;81:189–92.

    Article  PubMed  Google Scholar 

  14. Hochhaus A. Educational session: managing chronic myeloid leukemia as a chronic disease. Hematol Am Soc Hematol Educ Program. 2011;2011:128–35.

    Article  Google Scholar 

  15. Muller MC, Cross NC, Erben P, Schenk T, Hanfstein B, Ernst T, et al. Harmonization of molecular monitoring of CML therapy in Europe. Leukemia. 2009;23:1957–63.

    Article  CAS  PubMed  Google Scholar 

  16. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;8(122):872–84.

    Article  Google Scholar 

  17. Kikuchi S, Muroi K, Takahashi S, Kawano-Yamamoto C, Takatoku M, Miyazato A, et al. Severe hepatitis and complete molecular response caused by imatinib mesylate: possible association of its serum concentration with clinical outcomes. Leuk Lymphoma. 2004;45:2349–51.

    Article  PubMed  Google Scholar 

  18. van Erp NP, Gelderblom H, Karlsson MO, Li J, Zhao M, Ouwerkerk J, et al. Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib. Clin Cancer Res. 2007;13:7394–400.

    Article  PubMed  Google Scholar 

  19. Ramanathan RK, Egorin MJ, Takimoto CH, Remick SC, Doroshow JH, LoRusso PA, et al. Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. J Clin Oncol. 2008;26:563–9.

    Article  CAS  PubMed  Google Scholar 

  20. Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119:1123–9.

    Article  CAS  PubMed  Google Scholar 

  21. Kantarjian H, Pasquini R, Lévy V, Jootar S, Holowiecki J, Hamerschlak N, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase study (START-R). Cancer. 2009;115:4136–47.

    Article  CAS  PubMed  Google Scholar 

  22. Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007;109:2303–9.

    Article  CAS  PubMed  Google Scholar 

  23. Montani D, Bergot E, Günther S, Savale L, Bergeron A, Bourdin A, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125:2128–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Oncology/Hematology/Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Lars Harbaum, Philippe Schafhausen & Djordje Atanackovic

  2. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Andreas Marx

  3. Private Practice for Oncology, Hamburg, Germany

    Eray Goekkurt

Authors
  1. Lars Harbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Marx
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eray Goekkurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philippe Schafhausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Djordje Atanackovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Djordje Atanackovic.

About this article

Cite this article

Harbaum, L., Marx, A., Goekkurt, E. et al. Treatment with dasatinib for chronic myeloid leukemia following imatinib-induced hepatotoxicity. Int J Hematol 99, 91–94 (2014). https://doi.org/10.1007/s12185-013-1474-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-013-1474-x

Keywords

Search

Navigation