The relationship between nucleated red blood cell count and erythrocyte indices in peripheral blood and disease prognosis in chronic lymphocytic leukemia patients

Objective: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western societies. The disease course is heterogeneous. Therefore, understanding the progression of the disease plays a crucial role in disease management, treatment planning, monitoring, and predicting the estimated survival time. To gain information about the prognosis of the disease, staging systems such as Rai and Binet, cytogenetic examinations, some laboratory parameters (e.g,LDH, B2 microglobulin), flow cytometric analyses (e.g., CD38, ZAP70), and lymphocyte doubling time are utilized. In this study, we aimed to examine the role of nucleated erythrocytes and other erythrocyte indices in predicting disease prognosis and their relationship with certain biomarkers that provide information about the prognosis of the disease. Methods: The electronic records, laboratory results, and imaging results of 163 patients with CLL who were followed up between January 2018 and December 2023 at the adult hematology clinics of Çukurova University Medical Faculty Hospital and the Adana City Training and Research Hospital of the Ministry of Health were retrospectively reviewed. Demographic data such as age and gender, as well as hemogram values, biochemical values, 17p deletion status, bone marrow biopsy results, and comorbidity status were recorded. For analysis, patients were divided into two groups: those who required treatment and those who did not. Additionally, stages were calculated and grouped according to the Rai and Binet staging models. The relationship between nRBC and RDW, which are reported automatically in complete blood counts, and the recorded data was analyzed. Findings: The average age of the patients was 62.49 ± 10.58 years, with 98 males (60.9%) and 65 females (39.9%). The number of patients needing treatment was 69 (42.3%), while 94 patients (57.7%) were followed without any treatment. According to the RAI staging system, 16 patients (9.8%) were classified as low risk, 106 patients (65%) as intermediate risk, and 41 patients (25.2%) as high risk. According to the Binet staging system, 83 patients (50.9%) were in stage A, 40 patients (24.5%) in stage B, and 40 patients (24.5%) in stage C. Analysis revealed no significant difference in average nRBC count and nRBC% values between patients with and without comorbidities. The nRBC count and nRBC% values were significantly higher in those who required treatment. When patients were grouped according to the Rai staging system, nRBC count and nRBC% values were found to be higher in the high-risk group, and the results were statistically significant. When compared based on the Binet staging system, there was a significant difference in nRBC count and nRBC% values between groups, with higher values observed in stage C. No significant difference was found in average nRBC count and nRBC% values between 17p deletion negative and positive patients. A significant positive correlation was found between nRBC values and lymphocyte count, but no significant correlation was found between nRBC values and bone marrow lymphocyte percentage. RDW values were significantly higher in patients requiring treatment (p < 0.001). When patients were grouped according to the RAI staging system, RDW values showed significant differences between groups and were higher in the high-risk groups. A significant positive correlation was found between RDW and absolute lymphocyte count in peripheral blood, but no significant correlation was found between RDW and bone marrow lymphocyte percentage. Discussion and Conclusion: In patients with CLL, nRBC and RDW levels were found to be significantly higher in advanced-stage patients classified as high risk according to RAI and BINET staging systems and in those who developed a need for treatment. While prognostic markers are important for monitoring the disease in CLL patients, there is currently no marker that can definitively predict which patients will develop a need for treatment. Our findings suggest that nRBC and RDW from erythrocyte indices may be potential markers for predicting high-risk disease and the development of treatment needs in these cases. Additionally, a positive correlation was found between nRBC and RDW levels and the absolute lymphocyte count in peripheral blood. Although some studies in the literature have reported no association between lymphocytosis and advanced disease, others have shown a relationship. Both nRBC and RDW are routinely reported parameters in hemogram tests performed with current devices and are simple tests that do not require additional costs. Our findings indicate that these erythrocyte indices can be used as prognostic markers in CLL cases. Studies on RDW in CLL are limited, and no other studies on nRBC have been found; thus, our findings need to be supported by prospective, multi-center research involving large case series. In this regard, our study is expected to provide a foundation and inspiration for future research. Keywords: nRBC, Chronic lymphocytic leukemia, RDW, Prognosis