Cytokine Behavior and Its Clinical Impact in Chronic Lymphocytic Leukemia: A Real-Time Study in India
Authors: Bains Rupali , T Sudhahar , Naithani Manisha , Bakliwal Anamika , Kumar Karthik , Satadeve Paras , Gupta Adamya , Meena Kiran , Mirza Anissa Atif , Chandra Harish , Bahurupi Yogesh , Nath Uttam Kumar , Jayalingappa Karthik , Dalton Prisla , Singh Sashi , Ronanki Kavya , Mamgain Mukesh 
Published: December 2024

Chronic lymphocytic leukemia (CLL) remains a challenging disease to manage due to its heterogeneous nature and the lack of clarity regarding prognostic markers. This study aimed to clarify cytokine behavior in different stages (Binet and Modified Rai staging) and phases of CLL, particularly focusing on T helper cell dynamics, and investigate their potential as prognostic biomarkers.

Serum samples from 70 participants were analyzed for levels of cytokines Interleukin IL-2, IL-6, IL-10, and serum beta2 microglobulin using Sandwich ELISA and Chemiluminescence immunoassay methods. Clinical parameters, hematological profiles, and CLL disease stage were documented at baseline. Pearson chi-square, Fisher's exact tests, Mann-Whitney U tests, Kruskal-Wallis tests, and correlation analyses with P-values less than 0.05 were considered statistically significant.

In present study, 70 CLL patients were included. Median age recorded as 62 years. The proportion of the disease was 2.45 times higher in males. According to Modified Rai and Binet staging, the study participants were classified as low, moderate, or high risk at 17%, 37%, 46%, and 30%, 26%, and 44%, respectively.

The mean levels of IL-2, IL-6, IL-10, and serum beta2 microglobulin were 14.09 pg/ml, 42.92 pg/ml, 43.02 pg/ml, and 6.63 ug/L, respectively. Median levels were 7.23 pg/ml for IL-2, 44.74 pg/ml for IL-6, 31.11 pg/ml for IL-10, and 7.29 ug/L for serum beta2 microglobulin. IL-2 positively correlated with haemoglobin and platelet count but negatively correlated with lymphocyte count and serum LDH levels. Conversely, IL-6, IL-10 and Sβ2M were positively correlated with lymphocyte count and serum LDH levels but negatively correlated with haemoglobin and platelet count with p value of 0.0001.

Comparison across Modified Rai and Binet staging revealed decreasing IL-2 levels (range 35.68pg/ml to 3.55mg/ml, p value 0.00001) and increasing IL-6 (15.05pg/ml to 58.95pg/ml, p value 0.03), IL-10 (2.11pg/ml to 76.11pg/ml, p value 0.00001), and Sβ2M values (2.96ug/ml to 8.17ug/ml, p value 0.00001) with disease progression from Low to Intermediate and High risks groups. IL-6 and IL-10 has been found significant positively correlated (p value 0.00001) while IL-2 negatively correlated (p value 0.00001) with Sβ2M levels in the study patients.

These findings underscore the complex link between cytokines and CLL progression, with possible implications for prognosis and treatment. Our study found that blood levels of IL-6, IL-10, and Sβ2M rose with CLL progression, as did Interleukin-2 in the early stages of the disease. Furthermore, cytokine levels should be evaluated as a novel clinical prognostic marker for predicting early disease load and an aggressive treatment regimen to improve CLL patients' 5-year survival rates. In the coming years, cytokine levels may play an important role in treatment selection and delivering good treatment-free survival in CLL.