Skip to main content

Advertisement

Log in

Molecular responses of late chronic phase chronic myeloid leukemia patients after achieving complete cytogenetic responses with imatinib treatment: a 6-year follow-up

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

To explore the long-term efficacy of imatinib to chronic myeloid leukemia, a total of 46 late chronic phase (CP) patients were assessed after achieving complete cytogenetic response (CCyR). The median duration of imatinib treatment was 68 (61–74) months. Two hundred fifty-three bone marrow samples were detected BCR–ABL messenger RNA (mRNA) levels by TaqMan-based real-time quantitative reverse transcription–polymerase chain reaction. The median time when CCyR was first achieved was eight (3–72) months. Thirty-four patients achieved major molecular response (MMoR), and their median time when MMoR was first achieved was 35 (3–65) months. More patients achieving CCyR within 18 months obtained MMoR than those after 18 months (85% vs 42%, p = 0.006). One patient progressed into blastic crisis, and four patients suffered cytogenetic relapse later. The estimated 6-year event-free survival (EFS) rate of all patients was 81%. The BCR–ABL mRNA levels at the time of first CCyR of relapsed patients were significantly higher than those in continuous CCyR (p = 0.011). The 6-year estimated EFS rate of MMoR patients was significantly higher than that of non-MMoR patients (100% vs 44%, p = 0.0001). Achieving CCyR within 18 months had a higher probability of achieving MMoR within 6 years. The 6-year estimated EFS rate was significantly higher for patients achieving CCyR within 12 months than those after 12 months (97% vs 55%, p = 0.05). The time when MMoR was first achieved did not affect 6-year estimated EFS. Therefore, imatinib could induce most late CP patients to achieve long-term durable responses after achieving CCyR. Both the time when CCyR was first achieved and the depth of BCR–ABL reduction after CCyR are relevant to long-term EFS.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Reference

  1. Rowley JD (1973) A new consistent abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293 doi:10.1038/243290a0

    Article  PubMed  CAS  Google Scholar 

  2. Shtivelman E, Lifshitz B, Gale RP, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315:550–554 doi:10.1038/315550a0

    Article  PubMed  CAS  Google Scholar 

  3. Jabbour E, Cortes JE, Giles FJ, O’Brien S, Kantarjian HM (2007) Current and emerging treatment options in chronic myeloid leukemia. Cancer 109:2171–2181 doi:10.1002/cncr.22661

    Article  PubMed  CAS  Google Scholar 

  4. Mughal TI, Yong A, Szydlo RM, Dazzi F, Olavarria E, van Rhee F et al (2001) Molecular studies in patients with chronic myeloid leukaemia in remission 5 years after allogeneic stem cell transplant define the risk of subsequent relapse. Br J Haematol 115:569–574 doi:10.1046/j.1365-2141.2001.03155.x

    Article  PubMed  CAS  Google Scholar 

  5. Kantarjian HM, O’Brien S, Cortes JE, Shan J, Giles FJ, Rios MB et al (2003) Complete cytogenetic and molecular responses to interferon alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 97:1033–1041 doi:10.1002/cncr.11223

    Article  PubMed  CAS  Google Scholar 

  6. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417 doi:10.1056/NEJMoa062867

    Article  PubMed  CAS  Google Scholar 

  7. Qin YZ, Liu YR, Zhu HH, Li JL, Ruan GR, Zhang Y et al (2008) Different kinetic patterns of BCR–ABL transcript levels in imatinib-treated chronic myeloid leukemia patients after achieving complete cytogenetic response. Int J Lab Hematol 30:317–323

    Article  PubMed  CAS  Google Scholar 

  8. Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML et al (2003) Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 349:1423–1432 doi:10.1056/NEJMoa030513

    Article  PubMed  CAS  Google Scholar 

  9. Paschka P, Muller MC, Merx K, Kreil S, Schoch CB, Lahaye T et al (2003) Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission. Leukemia 17:1687–1694 doi:10.1038/sj.leu.2403033

    Article  PubMed  CAS  Google Scholar 

  10. Marin D, Kaeda J, Szydlo R, Saunders S, Fleming A, Howard J et al (2005) Monitoring patients in complete cytogenetic remission after treatment of CML in chronic phase with imatinib: patterns of residual leukemia and prognostic factors for cytogenetic relapse. Leukemia 19:507–512

    PubMed  CAS  Google Scholar 

  11. Palandri F, Iacobucci I, Martinelli G, Amabile M, Poerio A, Testoni N et al (2008) Long-term outcome of complete cytogenetic responders after imatinib 400 mg in late chronic phase, philadelphia-positive chronic myeloid leukemia: the GIMEMA Working Party on CML. J Clin Oncol 26:106–111 doi:10.1200/JCO.2007.13.2373

    Article  PubMed  CAS  Google Scholar 

  12. O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F et al (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994–1004 doi:10.1056/NEJMoa022457

    Article  PubMed  CAS  Google Scholar 

  13. Kantarjian H, Cortes J, O’Brien S, Luthra R, Giles F, Verstovsek S et al (2004) Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferonalpha. Blood 104:1979–1988 doi:10.1182/blood-2004-02-0711

    Article  PubMed  CAS  Google Scholar 

  14. Hughes T, Branford S (2006) Molecular monitoring of BCR–ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev 20:29–41 doi:10.1016/j.blre.2005.01.008

    Article  PubMed  CAS  Google Scholar 

  15. Rosti G, Martinelli G, Bassi S, Amabile M, Trabacchi E, Giannini B et al (2004) Molecular response to imatinib in late chronic-phase chronic myeloid leukemia. Blood 103:2284–2290 doi:10.1182/blood-2003-07-2575

    Article  PubMed  CAS  Google Scholar 

  16. Iacobucci I, Saglio G, Rosti G, Testoni N, Pane F, Amabile M et al (2006) Achieving a major molecular response at the time of a complete cytogenetic response (CCgR) predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients. Clin Cancer Res 12:3037–3042 doi:10.1158/1078-0432.CCR-05-2574

    Article  PubMed  CAS  Google Scholar 

  17. Hochhaus A, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J et al (2008) 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- treatment. Blood 111:1039–1043 doi:10.1182/blood-2007-07-103523

    Article  PubMed  CAS  Google Scholar 

  18. Iacobucci I, Rosti G, Amabile M, Poerio A, Soverini S, Cilloni D et al (2006) Comparison between patients with Philadelphia-positive chronic phase chronic myeloid leukemia who obtained a complete cytogenetic response within 1 year of imatinib therapy and those who achieved such a response after 12 months of treatment. J Clin Oncol 24:454–459 doi:10.1200/JCO.2005.03.2011

    Article  PubMed  CAS  Google Scholar 

  19. Goldman J (2005) Monitoring minimal residual disease in BCR–ABL-positive chronic myeloid leukemia in the imatinib era. Curr Opin Hematol 12:33–39 doi:10.1097/01.moh.0000148551.93303.9e

    Article  PubMed  CAS  Google Scholar 

  20. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F et al (2006) Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 108:1809–1820 doi:10.1182/blood-2006-02-005686

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to ShanShan Chen or YanRong Liu.

Additional information

Declaration: We declare that the experiments comply with the current laws in China and they were performed inclusive of ethics approval.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qin, Y., Jiang, B., Jiang, Q. et al. Molecular responses of late chronic phase chronic myeloid leukemia patients after achieving complete cytogenetic responses with imatinib treatment: a 6-year follow-up. Ann Hematol 88, 37–41 (2009). https://doi.org/10.1007/s00277-008-0548-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-008-0548-y

Keywords

Navigation