Skip to main content
SpringerLink
Log in

Successful Treatment with Imatinib Mesylate of a CML Patient in Megakaryoblastic Crisis with Severe Fibrosis

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

Abstract

The prognosis of patients with chronic myeloid leukemia in blastic crisis (CML-BC) remains extremely poor, and multiagent chemotherapy regimens commonly used to treat acute leukemia offer only short-term benefits. Therefore, the advent of the novel molecularly targeted anticancer agent imatinib mesylate is a breakthrough in CML therapy. We present a CML patient in megakaryoblastic crisis with severe myelofibrosis, who was treated with imatinib at a dosage of 400 mg/day and achieved complete remission together with a marked regression of myelofibrosis after 1 month. The effect of imatinib on the long-term prognosis remains unclear, although the agent is clearly a promising drug for treating CML-BC even in cases of myelofibrosis.Int J Hematol. 2002; 76: 349-353.

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

Similar content being viewed by others

References

  1. Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia.N Engl J Med. 1999; 341: 164–172.

    Article  CAS  PubMed  Google Scholar 

  2. Sawyers CL. Chronic myeloid leukemia.N Engl J Med. 1999; 340: 1330–1340.

    Article  CAS  PubMed  Google Scholar 

  3. Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials: Chronic Myeloid Leukemia Trialists’ Collaborative Group.J Natl Cancer Inst. 1997; 89: 1616-1620.

  4. Sacchi S, Kantarjian HM, O’Brien S, et al. Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients.Cancer. 1999; 86: 2632–2641.

    Article  CAS  PubMed  Google Scholar 

  5. Hernandez-Boluda JC, Cervantes F, Alvarez A, Costa D, Montserrat E. Single-agent therapy with oral mercaptopurine for nonlymphoid blast crisis of chronic myeloid leukemia.Ann Hematol. 2001; 80: 516–520.

    Article  CAS  PubMed  Google Scholar 

  6. Kantarjian HM, Talpaz M, Keating MJ, et al. Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.Cancer. 1991; 68: 1201–1207.

    Article  CAS  PubMed  Google Scholar 

  7. Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia.J Clin Invest. 2000; 105: 3–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Deininger MW, Goldman JM, Lydon N, Melo JV. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells.Blood. 1997; 90: 3691–3698.

    PubMed  CAS  Google Scholar 

  9. Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor.Blood. 2000; 96: 925–932.

    PubMed  CAS  Google Scholar 

  10. Buchdunger E, Zimmermann J, Mett H, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative.Cancer Res. 1996; 56: 100–104.

    CAS  PubMed  Google Scholar 

  11. Buchdunger E, Zimmermann J, Mett H, et al. Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class.Proc Natl Acad Sci U S A. 1995; 92: 2558–2562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Carroll M, Ohno-Jones S, Tamura S, et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins.Blood. 1997; 90: 4947–4952.

    PubMed  CAS  Google Scholar 

  13. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors.J Pharmacol Exp Ther. 2000; 295: 139–145.

    PubMed  CAS  Google Scholar 

  14. Fang G, Kim CN, Perkins CL, et al. CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs.Blood. 2000; 96: 2246–2253.

    PubMed  CAS  Google Scholar 

  15. Gambacorti-Passerini C, le Coutre P, Mologni L, et al. Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+leukemic cells and induces apoptosis.Blood Cells Mol Dis. 1997; 23: 380–394.

    Article  CAS  PubMed  Google Scholar 

  16. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.Nat Med. 1996; 2: 561–566.

    Article  CAS  PubMed  Google Scholar 

  17. le Coutre P, Mologni L, Cleris L, et al. In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor.J Natl Cancer Inst. 1999; 9: 163–168.

    Article  Google Scholar 

  18. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.N Engl J Med. 2001; 344: 1031–1037.

    Article  CAS  PubMed  Google Scholar 

  19. Druker B. Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia.Semin Hematol. 2001; 38: 9–14.

    Article  CAS  PubMed  Google Scholar 

  20. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.N Engl J Med. 2001; 344: 1038–1042.

    Article  CAS  PubMed  Google Scholar 

  21. Thiesing JT, Ohno-Jones S, Kolibaba KS, Druker BJ. Efficacy of STI571, an abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against bcr-abl-positive cells.Blood. 2000; 96: 3195–3199.

    PubMed  CAS  Google Scholar 

  22. Bauermeister DE. Quantification of bone marrow reticulin: a normal range.Am J Clin Pathol. 1971; 72: 68–70.

    Google Scholar 

  23. Geary CG. The story of chronic myeloid leukaemia.Br J Haematol. 2000; 110: 2–11.

    Article  CAS  PubMed  Google Scholar 

  24. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia.Blood. 2000; 96: 3343–3356.

    PubMed  CAS  Google Scholar 

  25. Sattler M, Griffin JD. Mechanisms of transformation by the BCR/ABL oncogene.Int J Hematol. 2001; 73: 278–291.

    Article  CAS  PubMed  Google Scholar 

  26. Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study.Blood. 2002; 99: 3530–3539.

    Article  CAS  PubMed  Google Scholar 

  27. Kantarjian HM, Cortes J, O’Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase.Blood. 2002; 99: 3547–3553.

    Article  CAS  PubMed  Google Scholar 

  28. Beham-Schmid C, Apfelbeck U, Sill H, et al. Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis.Blood. 2002; 99: 381–383.

    Article  CAS  PubMed  Google Scholar 

  29. Tefferi A, Mesa RA, Gray LA, et al. Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia.Blood. 2002; 99: 3854–3856.

    Article  CAS  PubMed  Google Scholar 

  30. Yang M, Khachigian LM, Hicks C, Chesterman CN, Chong BH. Identification of PDGF receptors on human megakaryocytes and megakaryocytic cell lines.Thromb Haemost. 1997; 78: 892–896.

    Article  PubMed  CAS  Google Scholar 

  31. Kvasnicka HM, Thiele J, Schmitt-Graeff A, et al. Bone marrow features improve prognostic efficiency in multivariate risk classification of chronic-phase Ph(1+) chronic myelogenous leukemia: a multicenter trial.J Clin Oncol. 2001; 19: 2994–3009.

    Article  CAS  PubMed  Google Scholar 

  32. Thiele J, Kvasnicka HM, Schmitt-Graeff A, et al. Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study.Br J Haematol. 2000; 108: 64–71.

    Article  CAS  PubMed  Google Scholar 

  33. Hofmann WK, Vos S, Elashoff D, et al. Relation between resistance of Philadelphia-chromosome-positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and geneexpression profiles: a gene-expression study.Lancet. 2002; 359: 481–486.

    Article  CAS  PubMed  Google Scholar 

  34. von Bubnoff N, Schneller F, Peschel C, Duyster J. BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study.Lancet. 2002; 359: 487–491.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Nagoya, Japan

    Yuka Hirose, Hitoshi Kiyoi, Masanori Iwai & Tomoki Naoe

  2. Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

    Toshiya Yokozawa

  3. Department of Pathology, Nagoya University Hospital, Nagoya, Japan

    Masafumi Ito

Authors
  1. Yuka Hirose
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hitoshi Kiyoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masanori Iwai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshiya Yokozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masafumi Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoki Naoe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hitoshi Kiyoi.

About this article

Cite this article

Hirose, Y., Kiyoi, H., Iwai, M. et al. Successful Treatment with Imatinib Mesylate of a CML Patient in Megakaryoblastic Crisis with Severe Fibrosis. Int J Hematol 76, 349–353 (2002). https://doi.org/10.1007/BF02982695

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02982695

Key words

Search

Navigation