Prognostic factors for the progression of chronic lymphocytic leukemia

Objective: to determine a complex of the most significant prognostic factors in chronic lymphocytic leukemia (CLL) for the purpose of evaluation of the probability of the disease progression. Material and methods. The study included 127 CLL patients whose clinical and laboratory parameters (sizes of the lymph nodes, liver and spleen, general and biochemical blood tests, β2-microglobulin, thymidine kinase, tissue polypeptide antigen (TPA), immunophenotypic markers) had been evaluated at the setting of the diagnosis. As a result of a dynamic followup, the patients were divided into 2 groups: 71 patients who had been observed in the outpatient setting and had had no signs of CLL progression within 3 years of the followup (group 1), and 56 patients with clinical signs of the disease progression that had manifested themselves after 3 years of the followup (group 2). Results. The study has revealed statistically considerable differences (Mann-Whitney test) between the groups in the size of the lymph nodes, liver and spleen, in the Binet stages, leukocyte count, absolute values of lymphocytes, the counts of red blood cells, hemoglobin and platelets, as well as the levels of β2-microglobulin, thymidine kinase, TPA, and immunophenotypic markers of CD24, ZAP-70, and CD38 in the blood, which indicates the interconnection of the levels of these parameters at the setting of the diagnosis with subsequent rapid CLL progression. According to the results of the use of logistic regression and Cox regression analysis, 10 parameters showing the strongest interconnection between the progression and 3-year progression free survival (PFS) have been selected. The use of the step-by-step selection of variables has made it possible to formulate a qualitative Cox regression equation including 5 main parameters: β2-microglobulin, thymidine kinase, TPA, ZAP-70, and CD38, which is indicative of the possibility to use this combination of the markers to predict CLL progression. Conclusion: The prognostic value of the complex of the laboratory parameters (β2-microglobulin, thymidine kinase, TPA, ZAP-70, and CD38) has been determined to assess the probability of CLL progression at the setting of the diagnosis, which can be used for the determination of the management tactics and selection of the treatment scheme for these patients.

1. Rai KR, Jain P. Chronic lymphocytic leukemia – Then and now. American Journal of Hematology. 2016;91(3):330-40. doi: 10.1002/ajh.24282.

2. Свирновский АИ. Хронический лимфоцитар-ный лейкоз: парадигмы и парадоксы. Медицин-ские Новости. 2008;13:7-19.

3. Кравченко ДВ, Свирновский АИ. Хронический лимфоцитарный лейкоз: клиника, диагностика, лечение. Практическое пособие для врачей. Гомель, РБ; 2017. 117 с.

4. Claus R, Lucas D, Ruppert A, Williams K, Weng D, Patterson K, Zucknick M. Validation of ZAP-70 methylation and its relative significance in predict-ing outcome in chronic lymphocytic leukemia. Blood. 2014;124(1):42-48. doi: 10.1182/blood-2014-02-555722.

5. Chen Y, Ying M, Chen Y. Serum thymidinekinase 1 correlates to clinical stages and clinical reac-tions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings. International Journal of Clinical Oncology. 2010;15(4): 359-68.

6. Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukemia. Nature Reviews Cancer. 2010;10(1):37-50.

7. Hallek M, Cheson В, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner Н. iwCLL guidelines for diagnosis, indications for treatment, response as-sessment, and supportive management of CLL. Blood. 2018;131(25):2745-60.