Regional Evaluation of Tolerability and Efficacy of Imatinib Mesylate in Patients with Chronic Phase CML in Mashhad (Iran, Southwest Asia)

Zahra Mozaheb, Maeedeh Javani

Azad University, Mashhad, Iran.
Department of Hematology, Imam-Reza Hospital, Mashhad University of Medical Science, Mashhad, Iran.

DOI: 10.4236/health.2014.610113                

Abstract

Sixty patients with Chronic Myeloid Leukemia (CML) who were on oral imatinib were included in this study. The study aimed to evaluate patients characteristic, tolerability and efficacy and clinical outcome in Iranian patients who have been treated with generic imatinib. The median age of patients was 48 years, and the median follow up was 44 months. 94% of patients achieved complete hematologic response (CHR) during the 3 months of beginning imatinib, and after 12 - 24 months of imatinib therapy 46.8% achieved molecular response. The most common non-hematologic toxicity was fluid retention (64%), fatigue (43%) and moderate to severe hematologic side effect included anemia 10%, neutropenia 10%, and thrombocytopenia 6.6%. About 13% of patients transformed into accelerated phase (AP) or blastic crisis (BC) and the death rate during this period was 7%. In conclusion, there is heterogeneity in different areas in characteristic of CML (especially in age), and also response rate and side effect of patients with CML that treated with imatinib are different.

Keywords

CML, Imatinib, Adverse Effects, Response Rate

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Larson, R.A., Druker, B.J., Guilhot, F., O’Brien, S.G., Riviere, G.J., Krahnke, T., et al. (2008) Imatinib Pharmacokinetics and Its Correlation with Response and Safety in Chronic-Phase Chronic Myeloid Leukemia: A Subanalysis of the IRIS Study. Blood, 111, 4022-4028. http://dx.doi.org/10.1182/blood-2007-10-116475
[2]	Ali, R., Özkalemkas, F., Özçelik, T., Özkocaman, V., Ozan, ü., Kimya, Y., et al. (2005) Pregnancy under Treatment of Imatinib and Successful Labor in a Patient with Chronic Myelogenous Leukemia (CML): Outcome of Discontinuation of Imatinib Therapy after Achieving a Molecular Remission. Leukemia Research, 29, 971-973. http://dx.doi.org/10.1016/j.leukres.2005.01.009
[3]	Agis, H., Sperr, W., Herndlhofer, S., Semper, H., Pirc-Danoewinata, H., Haas, O., et al. (2007) Clinical and Prognostic Significance of Histamine Monitoring in Patients with CML during Treatment with Imatinib (STI571). Annals of Oncology, 18, 1834-1841. http://dx.doi.org/10.1093/annonc/mdm343
[4]	Druker, B.J., Talpaz, M., Resta, D.J., Peng, B., Buchdunger, E., Ford, J.M., et al. (2001) Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia. New England Journal of Medicine, 344, 1031-1037. http://dx.doi.org/10.1056/NEJM200104053441401
[5]	Hughes, T.P., Kaeda, J., Branford, S., Rudzki, Z., Hochhaus, A., Hensley, M.L., et al. (2003) Frequency of Major Molecular Responses to Imatinib or Interferon Alfa plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia. New England Journal of Medicine, 349, 1423-1432. http://dx.doi.org/10.1056/NEJMoa030513
[6]	Bixby, D. and Talpaz, M. (2010) Seeking the Causes and Solutions to Imatinib-Resistance in Chronic Myeloid Leukemia. Leukemia, 25, 7-22. http://dx.doi.org/10.1038/leu.2010.238
[7]	Mendizabal, A.M., Garcia-Gonzalez, P. and Levine, P.H. (2013) Regional Variations in Age at Diagnosis and Overall Survival among Patients with Chronic Myeloid Leukemia from Low and Middle Income Countries. Cancer Epidemiology, 37, 247-254. http://dx.doi.org/10.1016/j.canep.2013.01.002
[8]	Howlader, N., Noone, A., Krapcho, M., Neyman, N., Aminou, R., Altekruse, S., et al. (2012) SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). National Cancer Institute, Bethesda.
[9]	Amirzargar, A., Bagheri, M., Ghavamzadeh, A., Alimoghadam, K., Khosravi, F., Rezaei, N., et al. (2005) Cytokine Gene Polymorphism in Iranian Patients with Chronic Myelogenous Leukaemia. International Journal of Immunogenetics, 32, 167-171. http://dx.doi.org/10.1111/j.1744-313X.2005.00502.x
[10]	Hochhaus, A., O’Brien, S.G., Guilhot, F., Druker, B.J., Branford, S., Foroni, L., et al. (2009) Six-Year Follow-Up of Patients Receiving Imatinib for the First-Line Treatment of Chronic Myeloid Leukemia. Leukemia, 23, 1054-1061. http://dx.doi.org/10.1038/leu.2009.38
[11]	Moshfeghi, K., Nazemzadeh, N., Mehrzad, V., Hajiannejad, A. and Esmaili, F. (2013) Comparison of Effectiveness and Safety of Iranian-Made vs. Indian-Made Imatinib in Treatment of Chronic Myeloid Leukemia. Advanced Biomedical Research, 2, 17. http://dx.doi.org/10.4103/2277-9175.108000
[12]	Druker, B.J., Guilhot, F., O’Brien, S.G., Gathmann, I., Kantarjian, H., Gattermann, N., et al. (2006) Five-Year Follow-Up of Patients Receiving Imatinib for Chronic Myeloid Leukemia. New England Journal of Medicine, 355, 2408-2417. http://dx.doi.org/10.1056/NEJMoa062867
[13]	Cortes, J., Giles, F., O’Brien, S., Thomas, D., Garcia-Manero, G., Rios, M.B., et al. (2003) Result of High-Dose Imatinib Mesylate in Patients with Philadelphia Chromosome—Positive Chronic Myeloid Leukemia after Failure of Interferon-α. Blood, 102, 83-86. http://dx.doi.org/10.1182/blood-2003-01-0025
[14]	Kantarjian, H.M., Talpaz, M., O’Brien, S., Jones, D., Giles, F., Garcia-Manero, G., et al. (2006) Survival Benefit with Imatinib Mesylate versus Interferon-α-Based Regimens in Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia. Blood, 108, 1835-1840. http://dx.doi.org/10.1182/blood-2006-02-004325
[15]	Lucas, C.M., Wang, L., Austin, G.M., Knight, K., Watmough, S.J., Shwe, K.H., et al. (2008) A Population Study of Imatinib in Chronic Myeloid Leukaemia Demonstrates Lower Efficacy than in Clinical Trials. Leukemia, 22, 1963-1966. http://dx.doi.org/10.1038/leu.2008.225
[16]	Fraunfelder, F.W., Solomon, J., Druker, B.J., Esmaeli, B. and Kuyl, J. (2003) Ocular Side-Effects Associated with Imatinib Mesylate (Gleevec®). Journal of Ocular Pharmacology and Therapeutics, 19, 371-375. http://dx.doi.org/10.1089/108076803322279426
[17]	Breccia, M., Gentilini, F., Cannella, L., Latagliata, R., Carmosino, I., Frustaci, A., et al. (2008) Ocular Side Effects in Chronic Myeloid Leukemia Patients Treated with Imatinib. Leukemia Research, 32, 1022-1025. http://dx.doi.org/10.1016/j.leukres.2007.10.016
[18]	Deininger, M.W., O’Brien, S.G., Ford, J.M. and Druker, B.J. (2003) Practical Management of Patients with Chronic Myeloid Leukemia Receiving Imatinib. Journal of Clinical Oncology, 21, 1637-1647. http://dx.doi.org/10.1200/JCO.2003.11.143
[19]	Sánchez-Guijo, F.M., Durán, S., Galende, J., Boqué, C., Nieto, J.B., Balanzat, J., et al. (2011) Evaluation of Tolerability and Efficacy of Imatinib Mesylate in Elderly Patients with Chronic Phase CML: ELDERGLI Study. Leukemia Research, 35, 1184-1187. http://dx.doi.org/10.1016/j.leukres.2011.01.017
[20]	Druker, B.J. (2002) Imatinib and Chronic Myeloid Leukemia: Validating the Promise of Molecularly Targeted Therapy. European Journal of Cancer, 38, S70-S76. http://dx.doi.org/10.1016/S0959-8049(02)80606-2
[21]	Kantarjian, H., Sawyers, C., Hochhaus, A., Guilhot, F., Schiffer, C., Gambacorti-Passerini, C., et al. (2002) Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia. New England Journal of Medicine, 346, 645-652. http://dx.doi.org/10.1056/NEJMoa011573