Skip to main content

Advertisement

SpringerLink
Log in

Morphologic Changes in the Bone Marrow in Patients of Chronic Myeloid Leukemia (CML) Treated with ImatinibMesylate

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Imatinib mesylate (Gleevec) is an effective treatment for chronic myeloid leukemia (CML). Though cytogenetic and molecular analyses are essential disease monitoring parameters in CML bone marrow morphological response is not well defined. We examined marrow samples from 40 patients with CML which have at least 2 or more follow-up marrow. A significant positive correlation with complete cytogenetic response shown for normalization of cellularity (P = 0.0097), absence of dry tap (P = 0.0368) and abnormal megakaryocytes (P = 0.005), reduction of blasts (P = 0.019), basophils (P = 0.031), M:E index (P = 0.018) and fibrosis (P = 0.018). Morphological criteria for complete cytogenetic response in CML patients treated with Imatinib can be defined.Morphologic response is also of potential clinical value in addition to cytogenetic and molecular response in patients of CML treated with Imatinib.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Deininger MW, Vieira S, Mendiola R, Schultheis B, Goldman JM, Melo JV (2006) BCR-ABL tyrosine kinase activity regulates the expression of multiple genes implicated in the pathogenesis of chronic myeloid leukemia. Cancer Res 60:2049–2055

    Google Scholar 

  2. Hasserjian RP, Boecklin F, Parker S, Chase A, Dhar S, Zaiac M et al (2002) STI571 reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response. Am J ClinPathol 117:360–367

    CAS  Google Scholar 

  3. O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cerventes F et al (2003) Imatinib compared with interferon, low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994

    Article  PubMed  Google Scholar 

  4. Braziel RM, Launder TM, Druker BJ, Olson SB, Magenis RE, Mauro MJ et al (2002) Hematopathologic and cytogenetic findings in imatinibmesylate-treated chronic myelogenous leukemia patients: 14 months’ experience. Blood 100:435–441

    Article  PubMed  CAS  Google Scholar 

  5. Lugli A, Ebnoether M, Coqliatti SB, Gratwohl A, Passweg J, Hess U et al (2005) Proposal of a morphologic bone marrow response score for Imatinibmesylate treatment in chronic myelogenous leukemia. Hum Pathol 36:91–100

    Article  PubMed  CAS  Google Scholar 

  6. Deninger MWN (2005) Chronic myeloid leukemia: management of early stage disease. In: Berliner N, Lee SJ, Linenberger M, Bogelsang GB (eds) American Society of Hematology Education Program Book. Atlanta. American Society of Hematology, Georgia, pp 174–182

    Google Scholar 

  7. 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

    Article  PubMed  CAS  Google Scholar 

  8. The Italian Cooperative study Group on Chronic Myeloid Leukemia (1994) Interferon Alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med 330:820–825

    Google Scholar 

  9. Talpaz M, Kantarjian HM, Credie KB, Keating MJ, Trujillo J, Gutturman J (1987) Clinical investigation of human and interferon in chronic myelogenous leukemia. Blood 69:1280–1288

    PubMed  CAS  Google Scholar 

  10. The Benelux (1998) CML study group; randomized study on Hydroxyurea alone versus Hydroxyurea combined with low-dose Inteferon-2b for chronic myeloid leukemia. Blood 91:2713–2721

    Google Scholar 

  11. Manoharan A, Horsley R, Pitney WR (1979) The reticulin content of bone marrow in acute leukemia in adults. Br J Haematol 43:185–190

    Article  PubMed  CAS  Google Scholar 

  12. Kumar L, Sagar TG, Maitreyan V, Majhi U, Shanta V (1990) Chronic granulocytic leukemia. A study of 160 cases. J Asso Phys India 38:899–902

    CAS  Google Scholar 

  13. Joshi S, Sunitha P, Deshmukh C, Gujral S, Amre P, Nair CN (2008) Bone marrow morphological changes in patients of chronic myeloid leukemia treated with Imatinib mesylate. Indian J Cancer 45:45–49

    Article  PubMed  CAS  Google Scholar 

  14. Kerkela R, Grazette L, Yacobi R, lliescu C, Patten R, Beahm C et al (2006) Cardiotoxicity of the cancer therapeutic agent Imatinib mesylate. Nat Med 12:908–916

    Article  PubMed  Google Scholar 

  15. Bueso-Rarnos CE, Cortes J, Talpaz M, O ‘Brien S, Giles F, Rios MB et al (2004) Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia. Cancer 101(2):332–336

    Article  Google Scholar 

  16. Druker BJ, Talpaz M, Rest DJ, Penga B, Buchdunger E, Ford JM, Lydon NB et al (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037

    Article  PubMed  CAS  Google Scholar 

  17. Druker BJ, Sawyrers CL, Kantarijan H, Rest DJ, Reese SF, Ford JM et al (2001) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast phase of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344:1038–1042

    Article  PubMed  CAS  Google Scholar 

  18. Beham-Schmid C, Apfelbeck U, Sill H, Tsybrovsky O, Hofler G, Haas OA et al (2002) Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis. Blood 99:381–383

    Article  PubMed  CAS  Google Scholar 

  19. McNamara C, Grigg A, Szer J, Roberts A, Campbell L, Hoyt R et al (2003) Morphological effects of imatinibmesylate (STI571) on the bone marrow and blood of patients with Philadelphia chromosome (Ph) positive chronic myeloid leukaemia. Clin Lab Haematol 25:119–125

    Article  PubMed  CAS  Google Scholar 

  20. Frater JL, Tallman MS, Variakojis D, Druker BJ, Resta D, Riley MB et al (2003) Chronic myeloid leukemia following therapy with Imatinib mesylate. Bone marrow histopathology and correlation with genetic status. Am J ClinPathol 119:833–841

    Google Scholar 

  21. Peggs K, Mackinnon S (2003) Inatinib mesylate—the new gold standard for treatment of chronic myeloid leukemia. N Engl J Med 348:1048–1050

    Article  PubMed  Google Scholar 

  22. Gambacorti-Passerini C, le Coutre P, Mologni L, Fenelli M, Bertazzoll C, Marchesi E, Di Nicola M et al (1997) Inhibition of the Abl kinase activity blocks the proliferation of BCR-ABL + leukemic cells and induces apoptosis. Blood Cells Mol Dis 23:380–394

    Article  PubMed  CAS  Google Scholar 

  23. Kelsey PR, Geary CG (1988) Sea-blue histiocytes and Gaucher cells in bone marrow of patients with chronic myeloid leukaemia. J Clin Pathol 41:960–962

    Article  PubMed  CAS  Google Scholar 

  24. Srinivas U, Pillai LS, Kumar R, Pati HP, Saxena R (2007) Bone marrow aplasia-a rare complication of Imatinib therapy in CML patients. Am J Hematol 82:314–316

    Article  PubMed  Google Scholar 

  25. Senn L, Telenti A, Kovacsovics T, Meylan P (2005) Peritoneal tuberculosis as a possible complication of Imatinib therapy for chronic myelogenous leukemia L. ESCMID 36:1–2

    Google Scholar 

  26. Ram R, Gafter-Gvili A, Okon E, Pazgal L, Shpilbergo O, Raanani P (2008) Gelatinous transformation of bone marrow in chronic myeloid leukemia during treatment with Imatinib mesylate: a disease or a drug effect? Acta Haematol 119:104–107

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, 500082, India

    B. H. Srinivas, T. Roshni Paul, Shantveer G. Uppin, Megha S. Uppin & Rachel T. Jacob

  2. Department of Medical Oncology, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, 500082, India

    D. Raghunadharao

Authors
  1. B. H. Srinivas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Roshni Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shantveer G. Uppin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Megha S. Uppin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rachel T. Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Raghunadharao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Roshni Paul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Srinivas, B.H., Paul, T.R., Uppin, S.G. et al. Morphologic Changes in the Bone Marrow in Patients of Chronic Myeloid Leukemia (CML) Treated with ImatinibMesylate. Indian J Hematol Blood Transfus 28, 162–169 (2012). https://doi.org/10.1007/s12288-011-0136-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-011-0136-5

Keywords

Search

Navigation