RSS-Feed abonnieren

DOI: 10.1055/s-0045-1810082
Chronic Myelogenous Leukemia Patients on Tyrosine Kinase Inhibitors—Hematological Changes and Correlation with European Leukemia Network Response Criteria
Funding None.

Abstract
Introduction
Chronic myeloid leukemia (CML) patients receive tyrosine kinase inhibitor (TKI) therapy for long duration. In this study, we analyzed hematological changes and compared them with hematological and cytogenetic response in 542 CML patients on TKI therapy with a follow-up period of 84 months.
Objective
To study hematological changes in patients on TKI therapy.
Materials and Methods
CML patients on TKI therapy (imatinib, 400 mg) with a minimum follow-up of 6 months were enrolled over a period of 8 years. Response was evaluated as per European Leukemia Network guidelines.
Results
A total of 542 patients with CML were included in the study, with 507 (93.5%) being in chronic phase disease, 21 (4%) in accelerated phase, and 14 (2.5%) in blast crisis.
The median age of patients was 38 years (range: 14–77 years), with male:female ratio = 1.4:1 (males = 317, 58.5% and females = 225, 41.5%).
At 3 months, 90% patients achieved complete hematological response (CHR). Normalization of platelet count, total leucocyte count, marrow cellularity, and granulocytic hyperplasia occurred by 3rd month of TKI therapy in majority of patients. Even though platelet counts normalized by 3rd month, megakaryocytic hyperplasia in the marrow normalized by 12th month of TKI therapy only.
Cytopenias were invariably seen in all follow-up time points, with anemia and thrombocytopenia being most common. At 1 and 2 years, respectively, anemia was seen in 25 and 31% of patients, leucopenia in 3 and 1% patients, and thrombocytopenia in 7 and 4% patients. In addition, bicytopenia and pancytopenia, respectively, were seen in 14.5 and 3% patients at 1 year and in 9 and 4% patients at 2 years.
Marrow hypocellularity and lymphoid nodules were seen in nearly 20% patients during TKI therapy.
Marrow hypercellularity was seen in a higher proportion of patients who were in “not in complete hematological response” (NCHR) than those who had achieved CHR (e.g., NCHR vs. CHR: at 6 months = 62 vs. 14%; at 12 months = 73 vs. 2%, at 18 months = 71 vs 9%, at 24 months = 57% vs. nil, at 36 months = 56 vs. 11%, at 42 months = 75 vs. nil, and at 60 months = 50% vs. nil).
None of the peripheral blood and bone marrow parameters analyzed in our study were consistently different between optimal and nonoptimal cytogenetic (warning and failure) responders.
Conclusion
In this study, TKI-induced hematological changes were evaluated in CML patients.
The increased peripheral blood counts, marrow cellularity, and granulocytic hyperplasia seen at diagnosis normalized in 90% patients by 3rd month of TKI therapy.
In patients who achieved CHR versus NCHR, a higher proportion of NCHR patients showed bone marrow hypercellularity.
Between optimal and nonoptimal cytogenetic responders, none of the peripheral blood and bone marrow parameter was found to be significantly different.
During follow-up, TKI-induced hematological changes observed included cytopenia, marrow hypocellularity, and lymphoid nodules.
Keywords
chronic myelogenous leukemia - tyrosine kinase inhibitors - hematological changes - responsePatient's Consent
The authors certify that they have obtained all appropriate patient consent.
Publikationsverlauf
Artikel online veröffentlicht:
16. Juli 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 2000; 96 (10) 3343-3356
- 2 An X, Tiwari AK, Sun Y, Ding P-R, Ashby Jr CR, Chen Z-S. BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leuk Res 2010; 34 (10) 1255-1268
- 3 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; 100 (02) 435-441
- 4 Tanaka H, Nakashima S, Usuda M. Rapid and sustained increase of large granular lymphocytes and rare cytomegalovirus reactivation during dasatinib treatment in chronic myelogenous leukemia patients. Int J Hematol 2012; 96 (03) 308-319
- 5 Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect?. Crit Rev Oncol Hematol 2014; 89 (02) 242-247
- 6 Barak AF, Bonstein L, Lauterbach R, Naparstek E, Tavor S. Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?. Hematol Rep 2011; 3 (03) e29
- 7 Lugli A, Ebnoether M, Cogliatti SB. et al. Proposal of a morphologic bone marrow response score for imatinib mesylate treatment in chronic myelogenous leukemia. Hum Pathol 2005; 36 (01) 91-100
- 8 Srinivas BH, Paul TR, Uppin SG, Uppin MS, Jacob RT, Raghunadharao D. Morphologic changes in the bone marrow in patients of chronic myeloid leukemia (CML) treated with imatinib mesylate. Indian J Hematol Blood Transfus 2012; 28 (03) 162-169
- 9 Joshi S, Sunita P, Deshmukh C, Gujral S, Amre P, Nair CN. Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate. Indian J Cancer 2008; 45 (02) 45-49
- 10 Baccarani M, Deininger MW, Rosti G. et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013; 122 (06) 872-884
- 11 Bansal S, Prabhash K, Parikh P. Chronic myeloid leukemia data from India. Indian J Med Paediatr Oncol 2013; 34 (03) 154-158
- 12 Paul TR, Uppin SG, Uppin MS, Jacob RT, Rao DR, Rajappa SJ. Evaluation of cytopenias occurring in imatinib treated chronic myeloid leukemia (CML) patients. Indian J Hematol Blood Transfus 2010; 26 (02) 56-61