{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:14:34Z","timestamp":1783487674140,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by a highly heterogeneous clinical course, with some patients remaining stable for years while others require early treatment. Identifying reliable and easily accessible predictors of treatment requirement at diagnosis remains an important clinical challenge. Methods: This retrospective cohort study included 226 patients diagnosed with CLL between 2015 and 2024 at a tertiary care center. Baseline demographic, clinical, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses were performed to identify independent predictors of treatment requirement. A hierarchical mixed-effects model was constructed to account for temporal clustering across diagnostic periods. A clinical risk score was derived from independent predictors, using regression coefficient-based weighting, and its discriminative performance was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 226 patients were included (mean age: 62.4 \u00b1 13.8 years; 56.6% male). During follow-up, 104 patients (46.0%) required treatment. Lower hemoglobin and platelet levels, higher lymphocyte counts and LDH levels, and the presence of B symptoms, splenomegaly, and advanced disease stage were independently associated with treatment requirement. These associations remained significant in hierarchical modeling. The derived risk score demonstrated acceptable discriminative ability (AUC: 0.84; 95% CI: 0.79\u20130.89), with a cut-off value of \u22654 yielding a sensitivity of 81.7% and specificity of 73.8%. Conclusions: Baseline clinical and laboratory parameters are associated with treatment requirement in CLL. A combination of readily available variables may support risk stratification at diagnosis. The proposed risk score may provide a practical adjunct to routine clinical assessment, particularly in settings where advanced molecular testing is not readily available; however, external validation in independent cohorts is required before clinical implementation.<\/jats:p>","DOI":"10.3390\/diagnostics16132003","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"2003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Baseline Clinical and Laboratory Predictors of Treatment Requirement in Chronic Lymphocytic Leukemia: A Retrospective Cohort Study Using Hierarchical Modeling"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7397-1877","authenticated-orcid":false,"given":"Hasan","family":"G\u00f6ze","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, University of Health Sciences, Istanbul Basaksehir Cam and Sakura City Hospital, \u0130stanbul 34000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birg\u00fcl","family":"\u00d6ne\u00e7","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Duzce University, Duzce 81100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16096","DOI":"10.1038\/nrdp.2016.96","article-title":"Chronic lymphocytic leukaemia","volume":"3","author":"Kipps","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13045-021-01054-w","article-title":"Current and future treatment strategies in chronic lymphocytic leukemia","volume":"14","author":"Patel","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/annonc\/mdh408","article-title":"Assessing prognosis in patients with chronic lymphocytic leukemia a quarter of a century after Rai and Binet staging systems","volume":"15","author":"Montserrat","year":"2004","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"K\u00fc\u00e7\u00fckyurt Kaya, S., and Afacan \u00d6zt\u00fcrk, H.B. (2026). Prognostic Impact of Serum Albumin Levels at Diagnosis in Patients with Chronic Lymphocytic Leukemia. J. Clin. Med., 15.","DOI":"10.3390\/jcm15031315"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Perez-Carretero, C., Gonzalez-Gascon-y-Marin, I., Rodriguez-Vicente, A.E., Quijada-Alamo, M., Hernandez-Rivas, J.-A., Hernandez-Sanchez, M., and Hernandez-Rivas, J.M. (2021). The evolving landscape of chronic lymphocytic leukemia on diagnosis, prognosis and treatment. Diagnostics, 11.","DOI":"10.3390\/diagnostics11050853"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1590\/S1516-31802000000400002","article-title":"Prognosis related to staging systems for chronic lymphocytic leukemia","volume":"118","author":"Silva","year":"2000","journal-title":"Sao Paulo Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1080\/10428190600881322","article-title":"Evaluation of clinical staging in chronic lymphocytic leukemia- population-based study","volume":"47","author":"Apelgren","year":"2006","journal-title":"Leuk. Lymphoma"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1182\/blood.2019003453","article-title":"International Prognostic Score for Asymptomatic Early-Stage Chronic Lymphocytic Leukemia","volume":"135","author":"Condoluci","year":"2020","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pratiwi, L., Mashudi, F.H., Ningtyas, M.C., Sutanto, H., and Romadhon, P.Z. (2025). Genetic Profiling of Acute and Chronic Leukemia via Next-Generation Sequencing: Current Insights and Future Perspectives. Hematol. Rep., 17.","DOI":"10.3390\/hematolrep17020018"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Alotaibi, G., Aleem, A., Absi, A., Alaskar, A.S., Alfraih, F., Alhejazi, A., Almasari, A., Alzahrani, M.F., Motabi, I., and El Fakih, R. (2025). Clinical practice guidelines for the diagnosis and management of chronic lymphocytic leukemia in Saudi Arabia: Consensus statement by an expert panel. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1719364"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1002\/sim.7336","article-title":"Intermediate and advanced topics in multilevel logistic regression analysis","volume":"36","author":"Austin","year":"2017","journal-title":"Stat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1093\/eurheartj\/ehu207","article-title":"Towards better clinical prediction models: Seven steps for development and an ABCD for validation","volume":"35","author":"Steyerberg","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kwok, M., and Wu, C.J. (2021). Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.790004"},{"key":"ref_14","first-page":"55","article-title":"Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era","volume":"16","year":"2024","journal-title":"Pharmaceutics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3892\/mco.2021.2262","article-title":"Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage","volume":"14","author":"Attia","year":"2021","journal-title":"Mol. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, P., and El Hussein, S. (2022). Chronic Lymphocytic Leukemia Progression Diagnosis with Intrinsic Cellular Patterns via Unsupervised Clustering. Cancers, 14.","DOI":"10.3390\/cancers14102398"},{"key":"ref_17","first-page":"1747","article-title":"Chronic lymphocytic leukemia often arises by a multiclonal selection process","volume":"110","author":"Bagnara","year":"2025","journal-title":"Haematologica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11899-017-0366-1","article-title":"A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia","volume":"12","author":"Tsang","year":"2017","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1002\/ajh.26585","article-title":"Unusual complications in the management of chronic lymphocytic leukemia","volume":"97","author":"Gordon","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fattizzo, B., and Barcellini, W. (2020). Autoimmune Cytopenias in Chronic Lymphocytic Leukemia: Focus on Molecular Aspects. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01435"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cohen, J.A., Bomben, R., Pozzo, F., Tissino, E., H\u00e4rzschel, A., and Hartmann, T.N. (2020). An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy. Cancers, 12.","DOI":"10.3390\/cancers12040894"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23620","DOI":"10.18632\/oncotarget.25306","article-title":"A high LDH to absolute lymphocyte count ratio in patients with DLBCL predicts for a poor intratumoral immune response and inferior survival","volume":"9","author":"Keane","year":"2018","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Qi, J., Gu, C., Wang, W., Xiang, M., Chen, X., and Fu, J. (2021). Elevated Lactate Dehydrogenase Levels Display a Poor Prognostic Factor for Non-Hodgkin\u2019s Lymphoma in Intensive Care Unit: An Analysis of the MIMIC-III Database Combined with External Validation. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.753712"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Autore, F., Strati, P., Innocenti, I., Corrente, F., Trentin, L., Cortelezzi, A., Visco, C., Coscia, M., Cuneo, A., and Gozzetti, A. (2019). Elevated lactate dehydrogenase has prognostic relevance in treatment-na\u00efve patients affected by chronic lymphocytic leukemia with trisomy 12. Cancers, 11.","DOI":"10.3390\/cancers11070896"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ajh.27546","article-title":"Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy","volume":"100","author":"Hallek","year":"2025","journal-title":"Am. J. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ajh.26367","article-title":"Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures","volume":"96","author":"Hallek","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_27","first-page":"5446","article-title":"Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute\u2013Working Group 1996 guidelines","volume":"111","author":"Hallek","year":"2008","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Gasc\u00f3n, Y.M.I., Mu\u00f1oz-Novas, C., and Rodr\u00edguez-Vicente, A.E. (2021). From Biomarkers to Models in the Changing Landscape of Chronic Lymphocytic Leukemia: Evolve or Become Extinct. Cancers, 13.","DOI":"10.3390\/cancers13081782"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Alshemmari, S.H., AlSarraf, A., Kaempf, A., and Danilov, A.V. (2024). Prognostic impact of chronic lymphocytic leukemia comorbidity index in a young population: A real-world evidence study of a national gulf region cohort. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12343-1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jamaoncol.2025.5934","article-title":"Incidentally Detected Splenomegaly and Risk of Hematologic Cancer and Liver Disease","volume":"12","author":"Juhl","year":"2026","journal-title":"JAMA Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"International CLL-IPI Working Group (2016). An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): A meta-analysis of individual patient data. Lancet Oncol., 17, 779\u2013790.","DOI":"10.1016\/S1470-2045(16)30029-8"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1182\/blood-2003-07-2281","article-title":"Prognosis at diagnosis: Integrating molecular biologic insights into clinical practice for patients with CLL","volume":"103","author":"Shanafelt","year":"2004","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Molica, S., and Allsup, D. (2025). Chronic Lymphocytic Leukemia Care and Beyond: Navigating the Needs of Long-Term Survivors. Cancers, 17.","DOI":"10.3390\/cancers17010119"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/13\/2003\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:26:49Z","timestamp":1783484809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/13\/2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":33,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["diagnostics16132003"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16132003","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}