{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T22:55:12Z","timestamp":1769554512223,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Macrocytosis commonly develops during imatinib therapy, but its relationship with cytogenetic and molecular outcomes in chronic myeloid leukemia (CML) remains unclear. We investigated whether increases in mean corpuscular volume (MCV) during imatinib treatment are associated with response depth and treatment persistence. Methods: In this retrospective study, we analyzed 101 adults with chronic-phase CML treated with a stable imatinib dose of 400 mg\/day for at least 12 months. Patients with conditions that could confound MCV (hydroxyurea exposure, megaloblastic anemia, hypothyroidism, chronic liver disease, alcoholism) were excluded. Complete cytogenetic response (CCyR) and major molecular response (MMR) were assessed by conventional karyotyping and the BCR-ABL1 International Scale, respectively. Increased MCV was defined as MCV &gt; 100 fL after six months of therapy, persisting thereafter. Associations between MCV dynamics, response, and switching to second-generation tyrosine kinase inhibitors were evaluated. Results: Twenty patients (20%) developed increased MCV. Overall, 86 patients (85%) achieved CCyR and 70 (69%) achieved MMR. All patients with increased MCV attained CCyR, compared with 66 of 81 (81%) without MCV elevation (p = 0.037), while MMR rates were 90% versus 64% (p = 0.030). During a median follow-up of 69 months, treatment modification was required in 1 of 20 (5%) patients with increased MCV versus 25 of 81 (31%) in the non-increased group (p = 0.018). Conclusions: MCV elevation during imatinib therapy is associated with deeper molecular response and reduced need for treatment modification. MCV dynamics may serve as an inexpensive pharmacodynamic marker to support risk assessment and guide monitoring in chronic-phase CML.<\/jats:p>","DOI":"10.3390\/jcm15020908","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:21:40Z","timestamp":1769505700000},"page":"908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrocytosis as an Early Pharmacodynamic Marker of Imatinib Efficacy in Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-571X","authenticated-orcid":false,"given":"Fatih","family":"Yaman","sequence":"first","affiliation":[{"name":"Clinic of Hematology, Tokat Public Hospital, Tokat 60100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-1498","authenticated-orcid":false,"given":"Ibrahim Ethem","family":"Pinar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-784X","authenticated-orcid":false,"given":"Sevgi","family":"Isik","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir 26040, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4017-4668","authenticated-orcid":false,"given":"Filiz","family":"Yavasoglu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir 26040, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-2949","authenticated-orcid":false,"given":"Eren","family":"Gunduz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir 26040, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4434-4580","authenticated-orcid":false,"given":"Hava","family":"Uskudar Teke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir 26040, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0510-4733","authenticated-orcid":false,"given":"Neslihan","family":"Andic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir 26040, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","unstructured":"Society, A.C. (2019). Cancer Prevention & Early Detection Facts & Figures 2019\u20132020, American Cancer Society."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3109\/10428199309047856","article-title":"The Cytogenetic Scenario of Chronic Myeloid Leukemia","volume":"11","author":"Mitelman","year":"1993","journal-title":"Leuk. Lymphoma"},{"key":"ref_3","first-page":"3025","article-title":"Tyrosine kinase inhibitors in Ph chronic myeloid leukemia therapy: A review","volume":"17","author":"Shah","year":"2016","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/ejh.12356","article-title":"Impact of risk score calculations in choosing front-line tyrosine kinase inhibitors for patients with newly diagnosed chronic myeloid leukemia in the chronic phase","volume":"93","author":"Hu","year":"2014","journal-title":"Eur. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1038\/s41375-018-0136-7","article-title":"Validation of the EUTOS long-term survival score in a recent independent cohort of \u201creal world\u201d CML patients","volume":"32","author":"Geelen","year":"2018","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e24003","DOI":"10.1097\/MD.0000000000024003","article-title":"Higher red blood cell distribution width at diagnose is a simple negative prognostic factor in chronic phase-chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: A retrospective study","volume":"100","author":"Mao","year":"2021","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2147\/CMAR.S288589","article-title":"Higher Red Blood Cell Distribution Width is a Poor Prognostic Factor for Patients with Chronic Myeloid Leukemia","volume":"13","author":"Li","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1182\/blood-2003-05-1535","article-title":"Inhibitory effect of imatinib on normal progenitor cells in vitro","volume":"103","author":"Bartolovic","year":"2004","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1056\/NEJMoa022457","article-title":"Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia","volume":"348","author":"Guilhot","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1200\/JCO.2013.49.1118","article-title":"Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update","volume":"31","author":"Lyman","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sato, S., Ohata, E., Nakatani, E., Hawke, P., Sasaki, H., Nagai, E., Taki, Y., Nishida, M., Watanabe, M., and Ohata, K. (2025). High mean corpuscular volume as a predictor of esophageal cancer: A cohort study based on the Japanese Shizuoka Kokuho Database. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0318791"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ejca.2015.12.019","article-title":"Macrocytosis as a potential parameter associated with survival after tyrosine kinase inhibitor treatment","volume":"56","author":"Kloth","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mazzaschi, G., Lazzarin, A., Santoni, M., Trentini, F., Giorgi, U.D., Brighi, N., Tommasi, C., Puglisi, S., Caffo, O., and Kinspergher, S. (2023). Integrating red blood cell features and hemoglobin levels in metastatic renal cell carcinoma patients treated with pazopanib or cabozantinib: An easily exploitable prognostic score. Front. Biosci., 15.","DOI":"10.31083\/j.fbe1503020"},{"key":"ref_14","first-page":"405","article-title":"Correlation of Mean Corpuscular Volume with Clinical Features and Prognosis of Patients with Treatment-Related Acute Myeloid Leukemia","volume":"52","author":"Lyu","year":"2025","journal-title":"Cancer Res. Prev. Treat."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Todor, S.B., and Ichim, C. (2025). Microbiome Modulation in Pediatric Leukemia: Impact on Graft-Versus-Host Disease and Treatment Outcomes: A Narrative Review. Children, 12.","DOI":"10.3390\/children12020166"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.leukres.2009.04.017","article-title":"Mean cell volume can be an early predictor for the cytogenetic response of chronic myeloid leukemia patients treated with imatinib?","volume":"33","author":"Song","year":"2009","journal-title":"Leuk. Res."},{"key":"ref_17","first-page":"382","article-title":"Mean Corpuscular Volume Can Be a Predictor for Therapeutic Response of Patients with Chronic Myeloid Leukemia","volume":"26","author":"Lu","year":"2018","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1056\/NEJMoa030513","article-title":"Frequency of Major Molecular Responses to Imatinib or Interferon Alfa plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia","volume":"349","author":"Hughes","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1046\/j.1365-2141.1997.d01-1982.x","article-title":"Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period","volume":"96","author":"Savage","year":"1997","journal-title":"Br. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJMoa011573","article-title":"Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia","volume":"346","author":"Kantarjian","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1182\/blood-2006-02-004325","article-title":"Survival benefit with imatinib mesylate versus interferon-\u03b1\u2013based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia","volume":"108","author":"Kantarjian","year":"2006","journal-title":"Blood"},{"key":"ref_23","first-page":"4022","article-title":"Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: A subanalysis of the IRIS study","volume":"111","author":"Larson","year":"2008","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32846","DOI":"10.18632\/oncotarget.9055","article-title":"Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia","volume":"7","author":"Podhorecka","year":"2016","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/sj.leu.2400927","article-title":"The role of insulin (INS) and insulin-like growth factor-I (IGF-I) in regulating human erythropoiesis. Studies in vitro under serum-free conditions\u2013comparison to other cytokines and growth factors","volume":"12","author":"Ratajczak","year":"1998","journal-title":"Leukemia"},{"key":"ref_26","unstructured":"Nelson, K. (2021). Macrocytosis and Tki Efficacy in Chronic Myeloid Leukemia. [Ph.D. Thesis, Eshelman School of Pharmacy]."},{"key":"ref_27","first-page":"152","article-title":"Chronic myeloid leukemia in 2006: A perspective","volume":"91","author":"Mauro","year":"2006","journal-title":"Haematologica"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/908\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:32:39Z","timestamp":1769506359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jcm15020908"],"URL":"https:\/\/doi.org\/10.3390\/jcm15020908","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]}}}