American Journal of Cancer

, Volume 2, Issue 6, pp 439–454 | Cite as

Imatinib Mesylate

A Review of its Use in Chronic Myeloid Leukemia
  • Monique P. Curran
  • Katherine F. Croom
  • Karen L. Goa
Adis Drug Evaluation



Imatinib mesylate (Gleevec®, Glivec®) is an orally administered competitive inhibitor of the BCR-ABL tyrosine kinase created by the Philadelphia chromosome (Ph+) in chronic myeloid leukemia (CML).

In patients with newly diagnosed and previously untreated (apart from hydroxyurea and/or anagrelide) CML in the chronic phase, imatinib mesylate 400 mg/day, compared with interferon-α (IFNα) plus cytarabine, resulted in higher hematologic response (HR) and cytogenetic response (CR) rates and fewer patients progressing to the accelerated phase or blast crisis in a large comparative trial. Preliminary results indicate that, compared with IFNα plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher health-related quality of life (HR-QOL).

Imatinib mesylate was also effective in patients with chronic-phase CML refractory to or intolerant of treatment with IFNα (as 400 mg/day) and in those with blast-crisis or accelerated-phase CML (600 mg/day). In the latter groups, HR and CR rates were lower than those in patients with chronic phase CML.

Imatinib mesylate-associated adverse events were common in clinical trials, but were mostly mild to moderate in severity. The most frequently reported adverse events were superficial edema, nausea, muscle cramps, diarrhea, vomiting, and skin rash. Myelosuppression (thrombocytopenia and neutropenia) was also reported, especially in patients with advanced disease. In patients with previously untreated chronic-phase CML, serious adverse events (both hematologic and nonhematologic) were less common with imatinib mesylate than with IFNα plus cytarabine treatment.

Conclusion: Imatinib mesylate is a valuable therapy for patients with newly diagnosed Ph+ chronic-phase CML. It is better tolerated and produces higher HR, CR and freedom from progressive disease rates than conventional therapy with IFNα plus cytarabine. Preliminary results indicate that, compared with IFNα plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher HR-QOL. Imatinib mesylate is also effective in patients with accelerated-phase and blast-crisis CML, and patients with chronic-phase CML who have failed IFNα therapy. Given its efficacy and generally manageable adverse event profile, imatinib mesylate offers an important early treatment option for patients with CML.

Pharmacodynamic Properties

Imatinib mesylate blocks the tyrosine kinase activity associated with the Abelson (ABL) protein, selectively inhibits the proliferation and survival of leukemia cells expressing break cluster region (BCR)-ABL and suppresses the formation of BCR-ABL-induced tumors in murine models. In vitro studies suggest a synergistic or additive effect when imatinib mesylate is coadministered with other chemotherapy agents, including interferon-α (IFNα), cytarabine, doxorubicin, daunorubicin, and etoposide. Mechanisms of imatinib mesylate resistance include amplification of the BCR- ABL gene, overexpression of BCR-ABL, the development of point mutations in the catalytic domain of BCR-ABL and the development of novel chromosomal aberrations.

Pharmacokinetic Properties

Imatinib mesylate is absorbed rapidly and extensively after oral administration; peak plasma concentrations (Cmax) are reached in 2–4 hours and bioavailability is 98%. Mean steady-state Cmax was 2.3 mg/L following administration of imatinib mesylate 400mg once daily to patients with chronic myeloid leukemia (CML). Accumulation is 2- to 3-fold at steady state with once-daily administration. Imatinib mesylate is 95% protein bound, predominantly to albumin and α1-acid glycoprotein. Metabolism is mainly through the action of the cytochrome P450 (CYP) isoform CYP3A4. The main metabolite (N-demethylated piperazine derivative) has similar in vitro potency to the parent compound. In patients with CML, the elimination half-life of imatinib mesylate is 13–16 hours. Excretion is primarily via the feces.

CYP3A4 inducers (e.g. phenytoin) increase the metabolism of imatinib mesylate and CYP3A4 inhibitors (e.g. ketoconazole and erythromycin) decrease it. Imatinib mesylate may inhibit the metabolism of other substrates of CYP3A4 (e.g. simvastatin) as well as substrates of CYP2C9, CYP2D6 and CYP3A4/5.

Therapeutic Efficacy

Oral imatinib mesylate 400 mg/day was more effective than subcutaneous IFNα plus cytarabine in patients with newly diagnosed and previously untreated (apart from hydroxyurea and/or anagrelide) CML in early chronic-phase in a randomized, multicenter, open-label, phase III trial (median treatment duration of 19 months). The estimated 18-month rate of freedom from progression to accelerated-phase or blast-crisis CML was 97% in imatinib mesylate recipients and 92% in IFNα plus cytarabine recipients (p < 0.001). Major cytogenetic response (MCR) rates were 85% and 22%, complete cytogenetic response (CCR) rates were 74% and 9% and complete hematologic response (CHR) rates were 95% and 56%, respectively (all p < 0.001). Molecular response (assessed according to quantitative polymerase chain reaction [PCR]-negativity) occurred in some of the imatinib mesylate recipients who achieved CCR; a >3 log reduction in BCR-ABL/BCR% values was estimated to be achieved in 39% of imatinib mesylate recipients versus 2% of IFNα plus cytarabine recipients (p < 0.001) at 12 months. Preliminary results indicate that, compared with IFNα plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher health-related quality of life.

Imatinib mesylate 400 mg/day was effective in patients with chronic-phase CML who had failed treatment with IFNα. In the largest phase II trial (median treatment duration of 18 months), MCR was achieved in 60% of patients, CCR in 41% and CHR in 95%. The 18-month estimated progression-free and overall survival rate was 89% and 95%.

In patients with accelerated-phase CML (median treatment duration of 11 months), imatinib mesylate 600 mg/day (n = 119) was effective as shown by the proportion of patients with responses (MCR 28%, CCR 19%, hematologic response [HR] 71%); the estimated 12-month progression-free and overall survival rates were 67% and 78%. Moreover, in patients with myeloid blast-crisis CML (n = 229; median treatment duration 4 months), imatinib was also effective, although the response rate (MCR 16%, CCR 7%, HR 31%) and the estimated median survival time (6.9 months) and the estimated 12-month overall survival rate (32%) were lower than those in the trial in patients with accelerated-phase CML.


The most frequently reported imatinib mesylate-associated nonhematologic adverse events (superficial edema, nausea, muscle cramps, diarrhea, vomiting, and skin rash) were mostly mild to moderate in severity. Grade 3 or 4 hepatotoxicity occurred in <5% of imatinib mesylate recipients.

Myelosuppression (thrombocytopenia and neutropenia) was frequently reported in clinical trials, and was more common in patients with advanced disease. In recipients of imatinib mesylate, the incidence of grade 3 or 4 neutropenia or thrombocytopenia was approximately 2- to 3-fold higher in myeloid blast-crisis or accelerated-phase CML than in chronic-phase CML, and was approximately 2-fold less than that in recipients of IFNα plus cytarabine.

Dosage and Administration

Imatinib mesylate is indicated for the treatment of newly diagnosed patients with Philadelphia chromosome-positive CML. Imatinib mesylate is also indicated for the treatment of patients with CML in blast crisis, accelerated phase, or chronic phase after failure of IFNα.

The recommended dosage of imatinib mesylate is 400 mg/day for patients with chronic-phase CML and 600 mg/day for patients with accelerated-phase or blast-crisis CML. Dosage increases from 400 to 600 mg/day in patients with chronic-phase CML or from 600 to 800 mg/day in patients with accelerated-phase or blast-crisis CML may be considered in disease progression, if a satisfactory HR is not achieved after ≥3 months of treatment, if CR is not achieved after 6–12 months of treatment or if loss of previously achieved HR or CR occurs (in the absence of severe non-leukemia-related neutropenia or thrombocytopenia). The dosage of imatinib mesylate should be adjusted or treatment interrupted if severe neutropenia or thrombocytopenia occurs. If a severe nonhematologic adverse event occurs, imatinib mesylate should be withheld until the event resolves.


  1. 1.
    Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999 Apr 29; 340: 1330–40PubMedCrossRefGoogle Scholar
  2. 2.
    Griffin J. The biology of signal transduction inhibition: basic science to novel therapies. Semin Oncol 2001 Oct; 28(5 Suppl. 17): 3–8PubMedCrossRefGoogle Scholar
  3. 3.
    Kalidas M, Kantarjian H, Talpaz M. Chronic myelogenous leukemia. JAMA 2001 Aug 22; 286: 895–8PubMedCrossRefGoogle Scholar
  4. 4.
    Savage DG, Antman KH. Imatinib mesylate: a new oral targeted therapy. N Engl J Med 2002 Feb 28; 346(9): 683–93PubMedCrossRefGoogle Scholar
  5. 5.
    Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 2000 Nov 15; 96(10): 3343–56PubMedGoogle Scholar
  6. 6.
    Cortes J, Kantarjian H. Advanced-phase chronic myeloid leukemia. Semin Hematol 2003 Jan; 40(1): 79–86PubMedCrossRefGoogle Scholar
  7. 7.
    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 May; 2: 561–6PubMedCrossRefGoogle Scholar
  8. 8.
    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 Oct; 295(1): 139–45PubMedGoogle Scholar
  9. 9.
    Okuda K, Weisberg E, Gilliland DG, et al. ARG tyrosine kinase activity is inhibited by STI571. Blood 2001; 97(8): 2440–8PubMedCrossRefGoogle Scholar
  10. 10.
    Lyseng-Williamson K, Jarvis B. Imatinib. Drugs 2001; 61(12): 1765–74CrossRefGoogle Scholar
  11. 11.
    Croom KF, Perry CM. Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. Drugs 2003; 63(5): 513–22PubMedCrossRefGoogle Scholar
  12. 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 Dec 15; 90: 4947–52PubMedGoogle Scholar
  13. 13.
    Buchdunger E, Zimmerman 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: 100–4PubMedGoogle Scholar
  14. 14.
    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(19): 380–94PubMedCrossRefGoogle Scholar
  15. 15.
    Deininger MW, Goldman JM, Lydon N, et al. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 1997 Nov 1; 90(9): 3691–8PubMedGoogle Scholar
  16. 16.
    Beran M, Cao X, Estrov Z, et al. Selective inhibition of cell proliferation and BCR-ABL phosphorylation in acute lymphoblastic leukemia cells expressing 190-KD BCR-ABL protein by a tyrosine kinase inhibitor (CGP-57148) [abstract]. Blood 1997 Nov 15; 90 (Suppl. 1, Pt 1): 248aGoogle Scholar
  17. 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 Jan 20; 91(2): 163–8PubMedCrossRefGoogle Scholar
  18. 18.
    Kawaguchi Y, Jinnai I, Nagai K, et al. Effect of a selective Abl tyrosine kinase inhibitor, STI571, on in vitro growth of BCR-ABL-positive acute lymphoblastic leukemia cells. Leukemia 2001 Apr; 15: 590–4PubMedCrossRefGoogle Scholar
  19. 19.
    Hasserjian RP, Boecklin F, Parker S, et al. ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response. Am J Clin Pathol 2002 Mar; 117(3): 360–7PubMedCrossRefGoogle Scholar
  20. 20.
    Braziel RM, Launder TM, Druker BJ, et al. Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients: 14 months’ experience. Blood 2002 Jul 15; 100(2): 435–41PubMedCrossRefGoogle Scholar
  21. 21.
    Topaly J, Zeller WJ, Fruehauf S. Combination therapy with imatinib mesylate (STI571): synopsis of in vitro studies. Br J Haematol 2002 Oct; 119(1): 3–14PubMedCrossRefGoogle Scholar
  22. 22.
    Gambacorti-Passerini CB, Gunby RH, Piazza R, et al. Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol 2003; 4: 75–85PubMedCrossRefGoogle Scholar
  23. 23.
    Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001 Aug 3; 293(5531): 876–80PubMedCrossRefGoogle Scholar
  24. 24.
    leCoutre P, Tassi E, Varella-Garcia M, et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood 2000 Mar 1; 95: 1758–66PubMedGoogle Scholar
  25. 25.
    Branford S, Rudzki Z, Walsh S, 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 May 1; 99(9): 3472–5PubMedCrossRefGoogle Scholar
  26. 26.
    von Bubnoff N, Schneller F, Peschel C, et al. BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 2002 Feb 9; 359: 487–91CrossRefGoogle Scholar
  27. 27.
    Shah NP, Nicoll JM, Nagar B, et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2002 Aug; 2(2): 117–25PubMedCrossRefGoogle Scholar
  28. 28.
    Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002; 16: 2190–6PubMedCrossRefGoogle Scholar
  29. 29.
    Holtz MS, Slovak ML, Zhang F, et al. Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Blood 2002 May 15; 99(10): 3792–800PubMedCrossRefGoogle Scholar
  30. 30.
    Marley SB, Deininger MWN, Davidson RJ, et al. The tyrosine kinase inhibitor STI571, like interferon-alpha, preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors from patients with chronic myeloid leukemia. Exp Hematol 2000 May; 28: 551–7PubMedCrossRefGoogle Scholar
  31. 31.
    Marley SB, Davidson RJ, Lewis JL, et al. Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo. Leuk Res 2001 Nov; 25(11): 997–1002PubMedCrossRefGoogle Scholar
  32. 32.
    Druker BJ, Sawyers CL, Capdeville R, et al. Chronic myelogenous leukemia. Hematology (Am Soc Hematol Educ Program) 2001; 87–112Google Scholar
  33. 33.
    Deininger MW, O’Brien SG, Ford JM, et al. Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol 2003; 21(8): 1637–47PubMedCrossRefGoogle Scholar
  34. 34.
    Mahon FX, Deininger MWN, Schultheis B. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 2000; 96(3): 1070–9PubMedGoogle Scholar
  35. 35.
    Gambacorti-Passerini CB, Rossi F, Verga M, et al. Differences between in vivo and in vitro sensitivity to imatinib of Bcr/Abl+ cells obtained from leukemic patients. Blood Cells Mol Dis 2002 May 30; 28(3): 361–72PubMedCrossRefGoogle Scholar
  36. 36.
    Gambacorti-Passerini C, Zucchetti M, Russo D, et al. α1 Acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin Cancer Res 2003 Feb; 9(2): 625–32PubMedGoogle Scholar
  37. 37.
    Novartis Pharmaceuticals Corporation. Gleevec™ imatinib mesylate: full prescribing information. East Hanover (NJ): Novartis, 2002 FebGoogle Scholar
  38. 38.
    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 Apr 5; 344(14): 1031–7PubMedCrossRefGoogle Scholar
  39. 39.
    Reckmann AH, Fischer T, Peng B, et al. Effect of food on STI571 Glivec pharmacokinetics and bioavailability [abstract 1223]. Proceedings of the 37th Annual Meeting of the American Society of Clinical Oncology; 2001 May 12–15; San Francisco, CA; 20 (Pt 1): 307aGoogle Scholar
  40. 40.
    Leis JF, Stepan DE, Curtin PT, et al. Low penetration of imatinib (STI571) into the CSF indicates the need for standard CNS prophylaxis in patients with CML lymphoid blast crisis and Philadelphia chromosome positive ALL [abstract no. 590]. Blood 2001; 98 (11 Pt 1): 140aCrossRefGoogle Scholar
  41. 41.
    O’Brien SG, Peng B, Dutreix C, et al. A pharmacokinetic interaction of Glivec® and simvastatin, a cytochrome 3A4 substrate, in patients with chronic myeloid leukemia [abstract no. 593]. Blood 2001; 98 (11 Pt 1): 141aGoogle Scholar
  42. 42.
    O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348(11): 994–1004PubMedCrossRefGoogle Scholar
  43. 43.
    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 May 15; 99: 3530–9PubMedCrossRefGoogle Scholar
  44. 44.
    Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002 Mar 15; 99(6): 1928–37PubMedCrossRefGoogle Scholar
  45. 45.
    Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002 Feb 28; 346(9): 645–52PubMedCrossRefGoogle Scholar
  46. 46.
    Bassi S, Trabacchi E, Bonifazi F, et al. Imatinib (Glivec®) in patients with Ph+ chronic myeloid leukemia in chronic phase after interferon failure: results of a phase II trial of the Italian Cooperative Study Group on CML [abstract no. 3096]. Blood 2002; 100 (Pt 1): 783aGoogle Scholar
  47. 47.
    Cortes JE, Talpaz M, O’Brien S, et al. High rates of major cytogenetic response in patients with newly diagnosed chronic myeloid leukemia (CML) in early chronic phase treated with imatinib at 400 mg or 800 mg daily [abstract no. 350]. Blood 2002 Nov 16; 100 (11 Pt 1): 95aCrossRefGoogle Scholar
  48. 48.
    Trabacchi E, Bonifazi F, Bassi S, et al. Imatinib (Glivec®) in patients with Ph+ chronic myeloid leukemia in accelerated/blastic phase (AP/B): results of a phase II trial of the Italian Cooperative Study Group on CML (ICSG on CML) [abstract no. 2295]. Blood 2002; 100 (Pt 1): 584aGoogle Scholar
  49. 49.
    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 May 15; 99(10): 3547–53PubMedCrossRefGoogle Scholar
  50. 50.
    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 Apr 5; 344(14): 1038–42PubMedCrossRefGoogle Scholar
  51. 51.
    Arthur C, Fay K, Grigg A, et al. Imatinib treatment for advanced CML improves patients’ quality of life [abstract no. 4859]. Blood 2002 Nov 16; 100 (Pt 2): 327bCrossRefGoogle Scholar
  52. 52.
    Hughes T, Kaeda J, Branford S, et al. Molecular responses to imatinib (STI571) or interferon + Ara-C as initial therapy for CML; results in the IRIS Study [abstract no. 345]. Blood 2002 Nov 16; 100 (Pt 1): 93a–4aGoogle Scholar
  53. 53.
    Lange T, Niederwieser DW. Residual disease in chronic myeloid leukemia after induction of molecular remission. N Eng J Med 2003; 349(15): 1483–4CrossRefGoogle Scholar
  54. 54.
    Hahn EA, Sorensen MV, Hudgens SA, et al. Quality of life of patients with chronic phase chronic myeloid leukemia in the IRIS Study of interferon-alpha plus Ara-C vs imatinib (STI571, Glivec®, Gleevec™) [abstractno. 346]. Blood 2002 Nov 16; 100 (Pt 1): 94aGoogle Scholar
  55. 55.
    Reed SD, Radeva JI, Glendenning A, et al. Within-trial resource utilization and costs of patients randomized to treatment with imatinib (STI571) versus interferon-alpha (IFN-α) combined with cytarabine (Ara-C) in newly diagnosed patients with chronic myeloid leukemia in chronic phase [abstract no. 698]. Blood 2002 Nov 16; 100 (Pt 1): 187aGoogle Scholar
  56. 56.
    Hensley ML, Van Hoomissen IC, Krahnke T, et al. Imatinib in chronic myeloid leukemia (CML): outcomes in >7000 patients treated on expanded access program (EAP) [abstract no. 2328]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago, 579Google Scholar
  57. 57.
    Faderl S, Kantarjian HM, Talpaz M. Chronic myelogenous leukemia: update on biology and treatment. Oncology (Huntingt) 1999 Feb; 13(2): 169–80; discussion 181, 184Google Scholar
  58. 58.
    National Cancer Institute. Common Toxicity Criteria, Version 2.0 1999 Jun 1 [online]. Available from URL: http:// [Accessed 2003 Mar 30]
  59. 59.
    Novartis International AG. Data prove Glivec® is superior treatment for patients newly diagnosed with chronic myeloid leukemia [online]. Available from URL: http:// [Accessed 2002 Apr 5]
  60. 60.
    FDA. FDA approves gleevec for pediatric leukemia treatment [online]. Available from URL: http:// [Accessed 2003 Sep 10]
  61. 61.
    O’Dwyer M. Current use of imatinib in the treatment of chronic myeloid leukemia. Haematologica 2003 Mar; 88(3): 241–4PubMedGoogle Scholar
  62. 62.
    Peggs K, Mackinnon S. Imatinib mesylate-the new gold standard for treatment of chronic myeloid leukemia. N Engl J Med 2003; 348(11): 1048–50PubMedCrossRefGoogle Scholar
  63. 63.
    Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood 2001 Oct 1; 98(7): 2039–42PubMedCrossRefGoogle Scholar
  64. 64.
    Silver RT, Woolf SH, Hehlmann R, et al. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology. Blood 1999 Sep 1; 94(5): 1517–36PubMedGoogle Scholar
  65. 65.
    Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med 1994 Mar 24; 330(12): 820–5CrossRefGoogle Scholar
  66. 66.
    Allan NC, Richards SM, Shepherd PCA. UK Medical Research Council randomised, multicentre trial of interferon-α n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. UK Medical Research Council’s Working Parties for Therapeutic Trials in Adult Leukaemia. Lancet 1995 Jun 3; 345(8962): 1392–7PubMedCrossRefGoogle Scholar
  67. 67.
    Chronic Myeloid Leukemia Trialists’ Collaborative Group. Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials: J Natl Cancer Inst 1997 Nov 5; 89(21): 1616–20CrossRefGoogle Scholar
  68. 68.
    Benelux CML Study Group. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-α 2b for chronic myeloid leukemia. Blood 1998 Apr 15; 91(8): 2713–21Google Scholar
  69. 69.
    Guilhot F, Chastang C, Michallet M, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med 1997 Jul 24; 337(4): 223–9PubMedCrossRefGoogle Scholar
  70. 70.
    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 Dec 15; 86(12): 2632–41PubMedCrossRefGoogle Scholar
  71. 71.
    Mauro MJ, Kurilik G, Balleisen S, et al. Myeloid growth factors for neutropenia during imatinib mesylate (STI571) therapy for CML: preliminary evidence of safety and efficacy [abstract no. 584]. Blood 2001; 98: 139aGoogle Scholar
  72. 72.
    Goldman J. Implications of imatinib mesylate for hematopoietic stem cell transplantation. Semin Hematol 2001 Jul; 38(3 Suppl. 8): 28–34PubMedCrossRefGoogle Scholar
  73. 73.
    Sausville EA. Imatinib for chronic myelogenous leukaemia: a 9 or 24 carat gold standard? Lancet 2003; 361: 1400–1PubMedCrossRefGoogle Scholar
  74. 74.
    Cervantes F, Hernández-Boluda J-C, Odriozola J, et al. Imatinib mesylate (STI571) treatment in patients with chronic-phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation. Br J Haematol 2003 Feb; 120(3): 500–4PubMedCrossRefGoogle Scholar
  75. 75.
    Hess G, Siegert W, Kolb HJ, et al. A phase II open-label study to investigate the safety profile and potential of imatinib mesylate (Gleevec, STI-571) to restore molecular remissions and chimerism in patients with BCR-ABL-positive CML with minimal residual disease (MRD) post allogeneic BMT/SCT [abstract no. 665]. Blood 2002 Nov 16; 100 (Pt 1): 177a–8aCrossRefGoogle Scholar
  76. 76.
    Olavarria E, Craddock C, Dazzi F, et al. Imatinib mesylate (STI571) in the treatment of relapse of chronic myeloid leukemia after allogeneic stem cell transplantation. Blood 2002 May 15; 99(10): 3861–2PubMedCrossRefGoogle Scholar
  77. 77.
    Ullmann AJ, Beck J, Kolbe K, et al. Clinical and laboratory evaluation of patients treated with STI-571 (Gleevec™ after allogeneic and syngeneic stem cell transplantation with relapsed Philadelphia chromosome-positive leukemia [abstract no. 1685]. Blood 2001 Nov 16; 98 (Pt 1): 401aGoogle Scholar
  78. 78.
    Soiffer RJ, Galinsky I, DeAngelo D, et al. Imatinib mesylate (Gleevec) for disease relapse following allogeneic bone marrow transplantation [abstract no. 1682]. Blood 2001 Nov 16; 98 (Pt 1): 400aGoogle Scholar
  79. 79.
    Pfeifer H, Wassmann B, Scheuring U, et al. ST1571 (Glivec) in the treatment of patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation [abstract no. 0240]. Bone Marrow Transplant 2002 Mar; 29Suppl. 2: S34Google Scholar
  80. 80.
    Miller CB, Smith BD, Gore SD, et al. Imatinib (STI-571) for treatment of relapse after stem cell transplantation (SCT) [abstract no. 1683]. Blood 2001 Nov 16; 98 (Pt 1): 400a–1aCrossRefGoogle Scholar
  81. 81.
    Liesveld JL, Nichols D, Ifthikharuddin JJ, et al. Use of imatinib mesylate in CML patients autografted in the pre-imatinib mesylate era: a single center experience [abstract no. 5471]. Blood 2002 Nov 16; 100 (Pt 2): 473bGoogle Scholar
  82. 82.
    Deininger MWN, Schleuning M, Sayer H-G, et al. Allografting after imatinib therapy. No evidence for increased transplant-related mortality and favorable result in patients transplanted in remission. A retrospective study by the EBMT. [abstract no. 3097] Blood 2003; 100 (Pt 1): 783aGoogle Scholar
  83. 83.
    Rosti G, Trabacchi E, Bassi S, et al. Risk and early cytogenetic response to imatinib and interferon in chronic myeloid leukemia. Haematologica 2003 Mar; 88(3): 256–9PubMedGoogle Scholar
  84. 84.
    O’Dwyer ME, Mauro MJ, Kuyl JM, et al. Preliminary evaluation of the combination of imatinib mesylate (Gleevec) in combination with low dose interferon-alpha for the treatment of chronic phase CML [abstract no. 3513]. Blood 2001 Nov 16; 98: 846aGoogle Scholar
  85. 85.
    O’Brien S, Vallance SE, Craddock C, et al. PEGIntron and STI571 combination evaluation study (PISCES) in chronic phase chronic myeloid leukaemia [abstract no. 3512]. Blood 2001 Nov 16; 98: 846aGoogle Scholar
  86. 86.
    Druker BJ, Kantarjian HM, Talpaz M, et al. A phase I study of Gleevec (imatinib mesylate) administered concomitantly with cytosine arabinoside (Ara-C) in patients with Philadelphia positive chronic myeloid leukemia (CML) [abstract no. 3511]. Blood 2001 Nov 16; 98: 845a–6aGoogle Scholar
  87. 87.
    Cornelissen JJ, Verhoef GEG, Straetmans N, et al. A dose-escalating phase I/II study of imatinib (Glivec) and cytarabin in first chronic phase chronic myeloid leukemia. Blood 2002 Nov 16; 100 (Pt 1): 95aGoogle Scholar
  88. 88.
    Hocchaus A, Fischer T, Brummendorf TH. Imatinib (Glivec®) and pegylated interferon (α2a (Pegasys®) phase I/II combination study in chronic phase chronic myelogenous leukemia (CML) [abstract no. 616]. Blood 2002; 100 (Pt 1): 164a–5aGoogle Scholar
  89. 89.
    Martine G, Philippe R, Michel T, et al. Imatinib (Gleevec®) and cytarabine (ARA-C) is an effective regimen in Philadephia (Ph)-positive chronic myelogenous leukaemia (CML) chronic phase (CP) patients (pts) [abstract no. 351]. Blood 2002; 100 (Pt 1): 95aGoogle Scholar
  90. 90.
    Mauro MJ, O’Dwyer ME, Stone RM, et al. Preliminary evaluation of the combination of imatinib mesylate (Gleevec) with low dose Ara-C as initial therapy for newly diagnosed chronic phase CML [abstract no. 617]. Blood 2002; 100 (Pt 1): 165aGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Monique P. Curran
    • 1
  • Katherine F. Croom
    • 1
  • Karen L. Goa
    • 1
  1. 1.Adis International Inc.YardleyUSA

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