Determination of β2–microglobulin level as a prognostic marker of chronic lymphocytic leukemia
DOI:
https://doi.org/10.15587/2519-4798.2017.91280Keywords:
chronic lymphocytic leukemia, β2–microglobulin, prognostic marker, disease stage, treatment, survivalAbstract
Disease prediction is rather important for the modern medicine. In the age of new and complex prognostic markers, β2–microglobulin is still simple, but important survival predictor in chronic lymphocytic leukemia (CLL) patients. The use of new biological markers is very expensive and not available for routine analysis in all regions. In contrast, β2–MG is significantly cheaper and simpler in its realization, as well as it is affordable for many non-specialized laboratories.
Aim. To analyze β2–MG level prognostic significance and its correlation depending on the disease stage, tumor volume and response to treatment in CLL patients.
Methods. 98 CLL patients, 37 women aged 42-75 years (average age 62.5 years) and 61 men aged 38-82 years (average age 62.5 years) were examined by us.
All the patients had general clinical examination, lymphocytes immunophenotyping in peripheral blood or bone marrow – phenotype СD 5+, СD 19+, СD 20+, СD23+, β2–MG using ECLIA method (Electro-chemiluminescence immunoassay). Cobas 6000, Roche Diagnostics (Switzerland) analyzer and test system were used. Reference values were 0,8–2,2 mg/l.
Results. In result of the study of β2–MG level in chronic lymphocytic leukemia (CLL) patients on the different stages of the disease, it was found, that β2–MG level correlates with CLL stage, directly depends on tumor volume, and is a reliable prognostic marker of response to treatment in CLL patients. β2–MG level >3,5 mg/l in blood serum is a bad prognostic predictor, which points to the high risk of disease.
Conclusion. β2–MG level correlates with the disease stage, tumor volume, and is a reliable prognostic marker of response to treatment in CLL patients
References
- Rai, K., Sawitsky, A., Cronkite, E., Chanana, A. D., Levy, R. N., Pasternack, B. S. (1975). Clinical staging of chronic lymphocytic leukemia. Blood, 46 (2), 219–234.
- Binet, J., Auquier, A., Dighiero, G., Chastang, C., Piguet, H., Goasguen, J. et. al. (1981). A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, 48 (1), 198–206. doi: 10.1002/1097-0142(19810701)48:1<198::aid-cncr2820480131>3.0.co;2-v
- Gribben, J. (2014). Prognostic and predictive factors in chronic lymphocytic leukemia. EHA Learning Center; Hematology Education, 8 (1), 59–74.
- Shindiapina, P., Brown, J. R., Danilov, A. V. (2014). A new hope: novel therapeutic approaches to treatment of chronic lymphocytic leukaemia with defects in TP53. British Journal of Haematology, 167 (2), 149–161. doi: 10.1111/bjh.13042
- Truger, M. S., Jeromin, S., Weissmann, S., Dicker, F., Kern, W., Schnittger, S. et. al. (2014). Accumulation of adverse prognostic markers worsens prognosis in chronic lymphocytic leukaemia. British Journal of Haematology, 168 (1), 153–156. doi: 10.1111/bjh.13077
- Binet, J.-L. (2005). Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia. Blood, 107 (3), 859–861. doi: 10.1182/blood-2005-04-1677
- Tsimberidou, A., Tam, C., Wierda, W., Brien, S. O'., Lerner, S., Keating, M. J. (2007). Beta-2 microglobulin (B2M) is an independent prognostic factor for clinical outcomes in patients with CLL treated with frontline fludarabine, cyclophosphamide, and rituximab (FCR) regardless of age, creatinine clearance (CrCl). Journal of Clinical Oncology, 25 (18), 7034.
- Wierda, W. G., O’Brien, S., Wang, X., Faderl, S., Ferrajoli, A., Do, K.-A. et. al. (2007). Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood, 109 (11), 4679–4685. doi: 10.1182/blood-2005-12-051458
- Güssow, D., Rein, R., Ginjaar, I., Hochstenbach, F., Seemann, G., Kottman, A. et. al. (1987). The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. The Journal of Immunology, 139 (9), 3132–3138.
- Späti, B., Child, J. A., Kerruish, S. M., Cooper, E. H. (2009). Behaviour of Serum β2-Microglobulin and Acute Phase Reactant Proteins in Chronic Lymphocytic Leukaemia. Acta Haematologica, 64 (2), 79–86. doi: 10.1159/000207215
- Di Giovanni, S., Valentini, G., Carducci, P., Giallonardo, P. (2009). Beta-2-Microglobulin Is a Reliable Tumor Marker in Chronic Lymphocytic Leukemia. Acta Haematologica, 81 (4), 181–185. doi: 10.1159/000205558
- Hallek, M., Wanders, L., Ostwald, M., Busch, R., Senekowitsch, R., Stern, S. et. al. (1996). Serum β2-Microglobulin and Serum Thymidine Kinase are Independent Predictors of Progression-Free Survival in Chronic Lymphocytic Leukemia and Immunocytoma. Leukemia & Lymphoma, 22 (5-6), 439–447. doi: 10.3109/10428199609054782
- Gentile, M., Cutrona, G., Neri, A., Molica, S., Ferrarini, M., Morabito, F. (2009). Predictive value of 2-microglobulin (2-m) levels in chronic lymphocytic leukemia since Binet A stages. Haematologica, 94 (6), 887–888. doi: 10.3324/haematol.2009.005561
- Lai, R., O’Brien, S., Maushouri, T., Rogers, A., Kantarjian, H., Keating, M., Albitar, M. (2002). Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer, 95 (5), 1071–1075. doi: 10.1002/cncr.10772
- Shanafelt, T. D. (2003). Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL. Blood, 103 (4), 1202–1210. doi: 10.1182/blood-2003-07-2281
- Moreno, C., Montserrat, E. (2008). New prognostic markers in chronic lymphocytic leukemia. Blood Reviews, 22 (4), 211–219. doi: 10.1016/j.blre.2008.03.003
- Delgado, J., Pratt, G., Phillips, N., Briones, J., Fegan, C., Nomdedeu, J. et. al. (2009). Beta2-microglobulin is a better predictor of treatment-free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate. British Journal of Haematology, 145 (6), 801–805. doi: 10.1111/j.1365-2141.2009.07699.x
- Mozaheb, Z., NazarAbadi, M. H. H., Aghaee, M. A. (2012). Chronic Lymphocytic Leukemia and Prognostic Factors. Asian Pacific Journal of Cancer Prevention, 13 (7), 3009–3013. doi: 10.7314/apjcp.2012.13.7.3009
- Shanafelt, T. D., Jenkins, G., Call, T. G., Zent, C. S., Slager, S., Bowen, D. A. et. al. (2008). Validation of a new prognostic index for patients with chronic lymphocytic leukemia. Cancer, 115 (2), 363–372. doi: 10.1002/cncr.24004
- Hamblin, T., Davis, Z., Gardiner, A., Oscier, D. G., Stevenson, F. K. (1999). UnmutatedIg V (H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94 (6), 1848–1854.
- Döhner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Kröber, A., Bullinger, L. et. al. (2000). Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia. New England Journal of Medicine, 343 (26), 1910–1916. doi: 10.1056/nejm200012283432602
- Del Principe, M. I., Bo, M. D., Bittolo, T., Buccisano, F., Rossi, F. M., Zucchetto, A. et. al. (2015). Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia. Haematologica, 101 (1), 77–85. doi: 10.3324/haematol.2015.131854
- Hallek, M., Cheson, B. D., Catovsky, D., Caligaris-Cappio, F., Dighiero, G., Dohner, H. et. al. (2008). 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-Working Group 1996 guidelines. Blood, 111 (12), 5446–5456. doi: 10.1182/blood-2007-06-093906
- Pflug, N., Bahlo, J., Shanafelt, T. D., Eichhorst, B. F., Bergmann, M. A., Elter, T. et. al. (2014). Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood, 124 (1), 49–62. doi: 10.1182/blood-2014-02-556399
- Wierda, W. G., O’Brien, S., Wang, X., Faderl, S., Ferrajoli, A., Do, K.-A. et. al. (2011). Multivariable Model for Time to First Treatment in Patients With Chronic Lymphocytic Leukemia. Journal of Clinical Oncology, 29 (31), 4088–4095. doi: 10.1200/jco.2010.33.9002
- Tam, C. S., Seymour, J. F. (2014). A new prognostic score for CLL. Blood, 124 (1), 1–2. doi: 10.1182/blood-2014-05-575407
- Kutsch, N., Bahlo, N., Byrd, J. et. al. (2015). The international Prognostic Index for patients with CLL (CLL-IPI): An international meta-analysis. Journal of Clinical Oncology, 33. Available at: http://meetinglibrary.asco.org/content/146941-156
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