Predictive value of proinflammatory activation in prognosis of cardiovascular events after treatment of chronic lymphoid leukemia

Authors

  • B. B. Samura Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1210.2017.3.100614

Keywords:

interleukin-6, CD40-ligand, chronic lymphoid leukemia, inflammation, prognosis

Abstract

Aim: To evaluate the prognostic value of circulating interleukin-6 and CD40 ligand in patients after chronic lymphoid leukemia treatment.

Materials and Methods: 193 patients with chronic lymphoid leukemia after chemotherapy were included in the study. Observation period was up to 12 months. Blood plasma samples were taken for circulating levels of interleukin-6 and CD40 ligand measurements with the help of ELISA method.

Results: During observation period, 29 patients had progression of chronic lymphoid leukemia. 8 patients were excluded from the study due to their absence on the regular visit. Therefore, further analysis included 156 patients. 216 clinical events were recorded in 51 patients (32.7 %) with the following distribution: 122 cardiac arrhythmias, 16 cardiac ischemic events, 3 strokes, 30 chronic heart failures and 38 hospital admissions for cardiovascular reasons, 7 cardiovascular deaths, and 18 noncardiovascular deaths. Medians of interleukin-6 circulating levels in free-events subject cohort and subjects cohort with cardiovascular events were 0.78 ng/ml (95 % confidence interval [CI] = 0.61–1.86 ng/ml) and 1.50 ng/ml (95 % CI = 0.56–5.84 ng/ml) (p = 0.026) respectively. Medians of CD40 ligand circulating levels in free-events subject cohort and subjects cohort with cardiovascular events were 1.24 ng/ml (95 % CI = 0.76–3.20 ng/ml) and 2.88 ng/ml (95 % CI = 1.83–6.36 ng/ml) (p = 0.076) respectively. Interleukin-6 positively correlated with CD40 ligand (r = 0.33, p = 0.04).

The patients with elevated levels of both interleukin-6 and CD40 ligand had increased risk of cardiovascular events, whereas CD40 ligand, T2DM, hypertension, obesity, LVEF, and multi-vessel lesion did not.

Conclusions: Among patients who have been previously treated for chronic lymphoid leukemia, increased circulating interleukin-6 and CD40 ligand associated with increased cumulative cardiovascular events. Serum levels of interleukin-6 and CD40 ligand could be useful to predict the long-term outcome in patients with chronic lymphoid leukemia.

 

References

Kriachok, I. A. (2013) Khronicheskij limfolejkoz: novoe v lechenii. Podkhody k terapii pervoj linii i ikh eʹvolyuciya [Chronic lymphocytic leukemia: new in treatment. Approaches to the first-line treatment and their evolution]. Klinicheskaya onkologiya, 3(11), 121–129. [in Russian].

Andre, P., Prasad, K. S., Denis, C. V., He, M., Papalia, J. M., Hynes, R. O., et al. (2002) CD40L stabilises arterial thrombi by a beta 3 integrin-dependent mechanism. Nat. Med., 8, 247–252. doi: 10.1038/nm0302-247.

Antoniades, C., Bakogiannis, C., Tousoulis, D., Antonopoulos, A. S., & Stefanadis, C. (2009) The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J. Am. Coll. Cardiol., 54(8), 669–677. doi: 10.1016/j.jacc.2009.03.076.

Aue, G., Lozier, J. N., Tian, X. Cullinane, A. M., Soto, S, Samsel, L, McCoy, P., & Wiestner, A. (2011) Inflammation, TNFα and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia. Am. J. Hematol., 86(10), 835–840. doi: 10.1002/ajh.22114.

Chiorazzi, N., Rai, K. R., & Ferrarini, M. (2005) Chronic lymphocytic leukemia. N. Engl. J. Med., 352(8), 804–815.

Ferroni, P., Rosa, A., Di Franco, M., Palmirotta, R., Guadagni, F., Davì, G., et al. (2007) Prognostic significance of interleukin-6 measurement in the diagnosis of acute myocardial infarction in emergency department. Clin. Chim. Acta., 381(2), 151–156. doi: 10.1016/j.cca.2007.03.002.

Goicoechea, M., Quiroga, B., García de Vinuesa, S., Verdalles, U., Reque, J., Panizo, N., et al. (2012) Intraindividual interleukin-6 variations on the cardiovascular prognosis of patients with chronic renal disease. Ren. Fail., 34(8), 1002–1009. doi: 10.3109/0886022X.2012.696469.

Hassan, G. S., Merhi, Y., & Mourad, W. (2012) CD40 ligand: a neo-inflammatory molecule in vascular diseases. Immunobiology, 217(5), 521–532. doi: 10.1016/j.imbio.2011.03.010.

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.

Loffler, D., Brocke-Heidrich, K., Pfeifer, G., Stocsits, C., Hackermuller, J., Kretzschmar, A. K., et al. (2007) Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood, 110(4), 1330–1333. doi: 10.1182/blood-2007-03-081133.

Pan, J. P., Liu, T. Y., Chiang, S. C., Lin, Y. K., Chou, C. Y., Chan, W. L., & Lai, S. T. (2004) The value of plasma levels of tumor necrosis factor-alpha and interleukin-6 in predicting the severity and prognosis in patients with congestive heart failure. J. Chin. Med. Assoc., 67(5), 222–228.

de Lemos, J. A., Zirlik, A., Schönbeck, U., Varo, N., Murphy, S. A., Khera, A., et al. (2005) Associations between soluble CD40 ligand, atherosclerosis risk factors, and subclinical atherosclerosis: results from the Dallas Heart Study. Arterioscler. Thromb. Vasc. Biol., 25(10), 2192–2196. doi: 10.1161/01.ATV.0000182904.08513.60.

Yoon, J. Y., Lafarge, S., Dawe, D., Lakhi, S., Kumar, R., Morales, C., et al. (2012) Association of interleukin-6 and interleukin-8 with poor prognosis in elderly patients with chronic lymphocytic leukemia. Leuk. Lymphoma, 53(9), 1735–1742. doi: 10.3109/10428194.2012.666662.

Yoshioka, T., Funayama, H., Hoshino, H., Nakamura, T., Sugawara, Y., Kubo, N., et al. (2010) Association of CD40 ligand levels in the culprit coronary arteries with subsequent prognosis of acute myocardial infarction. Atherosclerosis, 213(1), 268–272.

doi: http://doi.org/10.1016/j.atherosclerosis.2010.07.044.

How to Cite

1.
Samura BB. Predictive value of proinflammatory activation in prognosis of cardiovascular events after treatment of chronic lymphoid leukemia. Zaporozhye Medical Journal [Internet]. 2017May5 [cited 2024Nov.2];(3). Available from: http://zmj.zsmu.edu.ua/article/view/100614

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Section

Original research