Skip to main content

Advertisement

SpringerLink
Log in

Imatinib and Patient-Related Outcomes in Chronic Myeloid Leukemia: A Single Centric Experience

  • Original Paper
  • Published:
SN Comprehensive Clinical Medicine Aims and scope Submit manuscript

Abstract

Imatinib is a signal transduction inhibitor useful in the management of chronic myeloid leukemia (CML). There is a dearth of evidence available concerning Imatinib and its associated outcomes in Indian CML patients. So, this study is aimed to assess the patient-associated outcome in CML. This observational study was conducted at Rajiv Gandhi Cancer Institute and Research Centre (RGCIRC), New Delhi, India, over a period of 18 months. The toxicity was evaluated through CTCAE v 4.0 (common terminology criteria for adverse events) and compared with patient-related outcomes. The EUTOS (European Treatment and Outcome Study) score was used to assess the complete cytogenetic response after 18 months. The data were analyzed through SPSS v 22. The mean age of the patients was 38.8 ± 6.4 years and 35.80% were female. The majority of the patients belong to the age group of 41–60 years. Among the BCR-ABL group patients, P210-kD (kilo Dalton) protein was found among 69 patients, P190-kD protein was found in 9 patients, while dual fusion transcript of P210-kD and P190-kD protein was found in only 3 patients. Neutropenia was the most common adverse event associated with P210-kD protein determined through CTCAE v 4.0. The CML patients with P210-kD protein were at higher risk while P190 kD and coexistence were at a lower risk of progression to blastic and further to accelerated phase based on EUTOS score. It is advisable to identify the BCR-ABL fusion transcript in CML with Imatinib treatment. However, multi-centric study with more number of patients may be warranted to reach conclusive facts.

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

Data Availability

The data or material for publication will be available after request.

Code Availability

The trial version of SPSS software was used for data analysis.

References

  1. 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: presented in part at the 43rd annual meeting of The American Society of Hematology, Orlando, FL, December 11, 2001. Blood. 2002;99:3530–9.

    Article  CAS  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: Cancer J Clin. 2015;65:5–29.

    Google Scholar 

  3. Ganesan P, Kumar L. Chronic myeloid leukemia in India. J Glob Oncol. 2017;3(1):64–71.

    Article  Google Scholar 

  4. Noens L, Van Lierde M-A, De Bock R, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113:5401–11.

    Article  CAS  Google Scholar 

  5. Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, Clark RE, Cortes JE, Deininger MW, Guilhot F, Hjorth-Hansen H. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966–84.

    Article  CAS  Google Scholar 

  6. 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;344:1031–7.

    Article  CAS  Google Scholar 

  7. Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1–positive chronic myeloid leukemia. Blood. 2009;113:1619–30.

    Article  CAS  Google Scholar 

  8. Lyu X, Yang J, Wang X, et al. A novel BCR-ABL1 fusion gene identified by next-generation sequencing in chronic myeloid leukemia. Mol Cytogenet. 2016;9:47.

    Article  Google Scholar 

  9. Arana-Trejo R, Sanchez ER, Ignacio-Ibarra G, et al. BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). Clin Lab Haematol. 2002;24:145–50.

    Article  CAS  Google Scholar 

  10. Reckel S, Hamelin R, Georgeon S, et al. Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics. Leukemia. 2017;31:1502.

    Article  CAS  Google Scholar 

  11. Bedi A, Zehnbauer BA, Barber JP, Sharkis SJ, Jones RJ. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood. 1994;83:2038–44.

    Article  CAS  Google Scholar 

  12. Yanagisawa K, Yamauchi H, Kaneko M, Kohno H, Hasegawa H, Fujita S. Suppression of cell proliferation and the expression of abcr-abl fusion gene and apoptotic cell death in a new human chronic myelogenous leukemia cell line, KT-1, by Interferon-α. Blood. 1998;91:641–8.

    Article  CAS  Google Scholar 

  13. Era T, Witte ON. Regulated expression of P210 Bcr-Abl during embryonic stem cell differentiation stimulates multipotential progenitor expansion and myeloid cell fate. Proc Natl Acad Sci. 2000;97:1737–42.

    Article  CAS  Google Scholar 

  14. Hoffmann VS, Baccarani M, Lindoerfer D, et al. The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib. Leukemia. 2013;27:2016–22.

    Article  CAS  Google Scholar 

  15. Granatowicz A, Piatek CI, Moschiano E, El-Hemaidi I, Armitage JD, Akhtari M. An overview and update of chronic myeloid leukemia for primary care physicians. Korean J Fam Med. 2015;36:197.

    Article  Google Scholar 

  16. Rostami G, Hamid M, Yaran M, Khani M, Karimipoor M. Incidence and clinical importance of BCR-ABL1 mutations in Iranian patients with chronic myeloid leukemia on imatinib. J Hum Genet. 2015;60:253.

    Article  CAS  Google Scholar 

  17. Hussain S, Najmi A, Singh A. Use of Cochrane evidence in supporting medical policies of oncology drugs in the United States. Eur J Cancer. 2017;72:S120.

    Article  Google Scholar 

  18. Hussain S, Singh A, Najmi A. Influence of Cochrane evidence on medical policies of oncology drugs in the United States. Value Health. 2016;19:A892.

    Article  Google Scholar 

  19. Singh A, Hussain S. OP134 Pan-Canadian private payers’ medical policies influenced by Cochrane evidence Canada. Int J Technol Assess Health Care. 2018;34:50-.

    Article  Google Scholar 

  20. Singh A, Hussain S, Najmi A. Are US private payers’ medical policies influenced by Cochrane evidence? Value Health. 2016;19:A815.

    Article  Google Scholar 

  21. Singh A, Hussain S, Najmi AK. Role of Cochrane reviews in informing US private payers’ policies. J Evid Based Med. 2017;10:293–331.

    Article  Google Scholar 

  22. Basch E, Iasonos A, McDonough T, et al. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006;7:903–9.

    Article  Google Scholar 

  23. Adler R, Viehmann S, Kuhlisch E, et al. Correlation of BCR/ABL transcript variants with patients’ characteristics in childhood chronic myeloid leukaemia. Eur J Haematol. 2009;82:112–8.

    Article  Google Scholar 

  24. Al-Achkar W, Moassass F, Youssef N, Wafa A. Correlation of p210 BCR-ABL transcript variants with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients. J BUON. 2016;21:444–9.

    Google Scholar 

  25. Prejzner W. Relationship of the BCR gene breakpoint and the type of BCR/ABL transcript to clinical course, prognostic indexes and survival in patients with chronic myeloid leukemia. Med Sci Monit. 2002;8:BR193-BR7.

  26. Singh AK, Hussain S, Ahmed R, Agrawal N, Bhurani D, Klugar M, Sharma M. Impact of imatinib treatment on renal function in chronic myeloid leukaemia patients. Nephrology. 2022;27(4):318–26.

    Article  CAS  Google Scholar 

  27. Hamid M, Bokharaei H. The frequency of BCR-ABL1 fusion transcripts in iranian patients with three different types of leukemia. Zahedan J Res Med Sci. 2017;19(7).

  28. Mir R, Ahmad I, Javid J, Zuberi M, Yadav P, Shazia R, Masroor M, Guru S, Ray PC, Gupta N, Saxena A. Simple multiplex RT-PCR for identifying common fusion BCR-ABL transcript types and evaluation of molecular response of the a2b2 and a2b3 transcripts to Imatinib resistance in north Indian chronic myeloid leukemia patients. Indian J Cancer. 2015;52(3):314.

    Article  Google Scholar 

  29. Kagita S, Mamidi TK, Digumarti L, Gundeti S, Digumarti R. Assessment of BCR-ABL1 fusion transcripts and their association with response to imatinib treatment in chronic myeloid leukemia patients. Indian J Med Paediatr Oncol. 2018;39:165.

    Article  Google Scholar 

  30. Chen Y, Peng C, Li D, Li S. Molecular and cellular bases of chronic myeloid leukemia. Protein Cell. 2010;1:124–32.

    Article  CAS  Google Scholar 

  31. Deb P, Chakrabarti P, Chakrabarty S, et al. Incidence of BCR-ABL transcript variants in patients with chronic myeloid leukemia: their correlation with presenting features, risk scores and response to treatment with imatinib mesylate. Indian J Med Paediatr Oncol. 2014;35:26.

    Article  Google Scholar 

  32. Ayatollahi H, Keramati MR, Kooshyar MM, Raiszadeh M, Shakeri S, Sadeghian MH. BCR-ABL fusion genes and laboratory findings in patients with chronic myeloid leukemia in northeast Iran. Caspian J Intern Med. 2018;9(1):65.

    Google Scholar 

Download references

Acknowledgements

The first author (Avinash Kumar Singh) would like to thank Sun Pharmaceuticals, India, for providing an assistantship for this project under the joint collaboration for the Ph.D. program with Jamia Hamdard, New Delhi, India.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Medicine (Division of Pharmacology), School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Avinash Kumar Singh & Mohammad Azharuddin

  2. Department of Hemato-Oncology & BMT Unit, Rajiv Gandhi Cancer Institute and Research Centre, Sector - 5, Rohini, Delhi, 110085, India

    Avinash Kumar Singh, Narendra Agrawal, Dinesh Bhurani & Rayaz Ahmed

  3. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Manju Sharma

Authors
  1. Avinash Kumar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Azharuddin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Narendra Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dinesh Bhurani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rayaz Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manju Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

First and second author — AKS and MA did the data analysis and manuscript writing. Third and fourth author — NA and DB have drafted the manuscript and table redrafting. Fifth and sixth author — RA and MS have resolved the query and drafted the methodology and manuscript.

Corresponding author

Correspondence to Manju Sharma.

Ethics declarations

Ethical Approval

This study has been approved by the Scientific Committee of Rajiv Gandhi Cancer Institute and Research Center with No. Res/SCM/38/2020/06 dated 07 February 2020.

Consent to Participate

The author has been taken consent for the study.

Consent for Publication

All the co-authors have given consent to participate for the publication.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Medicine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, A.K., Azharuddin, M., Agrawal, N. et al. Imatinib and Patient-Related Outcomes in Chronic Myeloid Leukemia: A Single Centric Experience. SN Compr. Clin. Med. 4, 165 (2022). https://doi.org/10.1007/s42399-022-01248-4

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s42399-022-01248-4

Keywords

Search

Navigation