International Journal of Hematology

, Volume 95, Issue 2, pp 209–213 | Cite as

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

  • Hidehiro Itonaga
  • Hideki Tsushima
  • Tomoko Hata
  • Emi Matsuo
  • Daisuke Imanishi
  • Yoshitaka Imaizumi
  • Yasuhisa Kawaguchi
  • Takuya Fukushima
  • Yuko Doi
  • Sayaka Mori
  • Shimeru Kamihira
  • Masao Tomonaga
  • Yasushi Miyazaki
Case Report

Abstract

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.

Keywords

Chronic myelogenous leukemia Imatinib Interferon T315I 

References

  1. 1.
    Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330–40.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervanteset F, et al. Imatinib compared with interferon and low dose cytarabine for newly diagnosed chronic phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004.PubMedCrossRefGoogle Scholar
  3. 3.
    Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.PubMedCrossRefGoogle Scholar
  4. 4.
    Silver RT, Talpaz M, Sawyers CL, Drucker BJ, Hochhaus A, Schiffer CA, et al. Four years of follow-up of 1027 patients with late chronic myeloid leukemia (CML) treated with imatinib in three large phase II trials. Blood. 2004;104:11a (abstract).Google Scholar
  5. 5.
    Saqlio G, Kim DW, Issaraqrisil 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.CrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    O’Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007;110:2242–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Soverini S, Colarossi S, Gnani A, Rosti G, Castagnetti F, Poerio A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12:7374–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Soverini S, lacobucci I, Baccarani M, Martinelli G. Targeted therapy and the T315I mutation in Philadelphia-positive leukemias. Haematologica. 2007;92:437–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Soverini S, Cloarossi S, Gnani A, Castagnetti F, Rosti G, Bosi C, et al. Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica. 2007;92:401–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Jabbour E, Cortes J, Kantarjian HM, Giralt S, Jones D, Jones R, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood. 2006;108:1421–3.PubMedCrossRefGoogle Scholar
  12. 12.
    Velev N, Cortes J, Champlin R, Jones D, Rondon G, Giralt S, et al. Stem cell transplantation for patients with chronic myeloid leukemia resistant to tyrosine kinase inhibitors with BCR-ABL kinase domain mutation T315I. Cancer. 2010;116:3631–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Nicolini FE, Basak GW, Soverini S, Martinelli G, Mauro MJ, Muller MC, et al. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias. Blood. 2011 (pii:2011-07-367326).Google Scholar
  14. 14.
    Nicolini FE, Mauro MJ, Martinelli G, Kim DW, Soverini S, Muller MC, et al. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood. 2009;114:5271–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Gontarewicz A, Balabanov S, Keller G, Colombo R, Graziano A, Pesenti E, et al. Simultaneous targeting of Aurora kinase and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I. Blood. 2008;111:4355–64.PubMedCrossRefGoogle Scholar
  16. 16.
    Quintas-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer. 2009;115:5382–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Gabert J, Beillard E, van der Velden VH, Bi W, Grimwade D, Pallisgaard N, et al. Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia—a Europe Against Cancer program. Leukemia. 2003;17:2318–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Branford S, Rudzki Z, Walsh S, Grigg A, Arthur C, Taylor K, et al. High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance. Blood. 2002;99:3472–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Polakova KM, Lopotova T, Klamova H, Moravcova J. High-resolution melt curve analysis: initial screening for mutations in BCR-ABL kinase domain. Leuk Res. 2008;38:1236–43.CrossRefGoogle Scholar
  20. 20.
    Yin CC, Cortes J, Galbincea J, Reddy N, Breeden M, Jabbour E, et al. Rapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays. Cancer Sci. 2010;101:2005–10.PubMedCrossRefGoogle Scholar
  21. 21.
    Chan WW, Wise SC, Kaufman MD, Ahn YM, Ensinger CL, Haack T, et al. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer Cell. 2011;19:556–68.PubMedCrossRefGoogle Scholar
  22. 22.
    Cheetham GM, Charlton PA, Golec JM, Pollard JR. Structural basis for potent inhibition of the Aurora kinase and a T315I multi-drug resistant mutant from Abl kinase by VX-680. Cancer Lett. 2007;251:323–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Crespan E, Radi M, Zanoli S, Schenone S, Botta M, Maga G. Dual Src and Abl inhibitors target wild type Abl and the AblT315I imatinib-resistant mutant with different mechanisms. Bioorg Med Chem. 2010;18:3999–4008.PubMedCrossRefGoogle Scholar
  24. 24.
    Sillaber C, Mayerhofer M, Bohm A, Vales A, Gruze A, Aichberger KJ, et al. Evaluation of antileukaemic effects of rapamycin in patients with imatinib-resistant chronic myeloid leukaemia. Eur J Clin Invest. 2008;38:43–52.PubMedCrossRefGoogle Scholar
  25. 25.
    de Lavallade H, Khorashad JS, Davis HP, Milojkovic D, Kaeda JS, Goldman JM, et al. Interferon-alpha or homoharringtonine as salvage treatment for chronic myeloid leukemia patients who acquire the T315I BCR-ABL mutation. Blood. 2007;110:2779–80.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Hidehiro Itonaga
    • 1
  • Hideki Tsushima
    • 2
  • Tomoko Hata
    • 2
  • Emi Matsuo
    • 3
  • Daisuke Imanishi
    • 2
  • Yoshitaka Imaizumi
    • 2
  • Yasuhisa Kawaguchi
    • 4
  • Takuya Fukushima
    • 2
  • Yuko Doi
    • 5
  • Sayaka Mori
    • 5
  • Shimeru Kamihira
    • 5
  • Masao Tomonaga
    • 6
  • Yasushi Miyazaki
    • 1
  1. 1.Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine UnitNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of HematologyNagasaki University HospitalNagasakiJapan
  3. 3.Department of Internal MedicineNagasaki National Medical CenterOhmuraJapan
  4. 4.Department of HematologyNagasaki Municipal Medical CenterNagasakiJapan
  5. 5.Department of Laboratory MedicineNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  6. 6.Department of HematologyJapanese Red-Cross Nagasaki Atomic Bomb HospitalNagasakiJapan

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