Chronic Myelogenous Leukemia Patients on Tyrosine Kinase Inhibitors—Hematological Changes and Correlation with European Leukemia Network Response Criteria

Abstract 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. To study hematological changes in patients on TKI therapy. 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. 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. 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.