Predicting Stage Progression in Binet Stage a Chronic Lymphocytic Leukemia

The variability in clinical course among patients with chronic lymphocytic leukemia (CLL) and the lack of consensus regarding follow-up and treatment strategies necessitate a prognostic model to determine patients at high risk of treatment initiation for prompt medical attention. Our study involved 121 participants diagnosed with Binet stage A CLL. Their demographic and clinical characteristics were retrospectively analyzed to determine their risk category according to the international prognostic scoring index for the early stage-CLL (IPS-E) model and evaluate the applicability of this prognostic approach in our young cohort from the Kuwait Cancer Control Center. Our cohort had a median age of 59 years and was predominantly male (70.2%). During the study period, 27 cases demonstrated progression to the first treatment. According to the IPS-E risk model, 17 cases were deemed low risk, 48 were intermediate risk, and 56 were high-risk. Of 121 tests to determine IGHV status, 60 patients have mutated IGHV. Multivariate Cox regression analysis revealed that patients with palpable lymph nodes and unmutated IGHV status confer a significantly higher risk of initiating treatment (hazards ratio of 3.12 and 3.36, respectively). In contrast, absolute lymphocyte count (ALC) was not statistically significant. A beta 2 microglobulin level >3.5 may also contribute toward progression to treatment through a higher disease burden. Based on the IPS-E model, high-risk patients fared worse compared to low- and intermediate-risk patients. However, the clinical impact of distinguishing the two latter risk groups may not be as significant. Although cases of CLL are relatively common, their clinical behavior regarding initiating the first treatment remains elusive. Nevertheless, the IPS-E risk model remains valuable in directing medical attention toward high-risk patients for optimal follow-up and treatment.

References 1. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-60

2. Hallek M, Shanafelt TD, Eichhorst B. Chronic lymphocytic leukaemia. Lancet. 2018;391(10129):1524-37

3. Condoluci A, Terzi di Bergamo L, Langerbeins P, Hoechstetter MA, Herling CD, De Paoli L, et al. International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia. Blood. 2020;135(21):1859-69.

4. Visentin A, Facco M, Gurrieri C, Pagnin E, Martini V, Imbergamo S, et al. Prognostic and Predictive Effect of IGHV Mutational Status and Load in Chronic Lymphocytic Leukemia: Focus on FCR and BR Treatments. Clin Lymphoma Myeloma Leuk. 2019;19(10):678-85.e4.

5. Tausch E, Schneider C, Robrecht S, Zhang C, Dolnik A, Bloehdorn J, et al. Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax. Blood. 2020;135(26):2402-12.

6. Brochet X, Lefranc MP, Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36(Web Server issue):W503-8.

No relevant conflicts of interest to declare.