Patient Stress Is Linked With Cancer Cell Proliferation and Elevated Cytokines in CLL

While it is well understood that psychological distress is a major side effect of cancer and its treatment, and that stress can have a strong impact on patients’ quality of life, a new study indicated that stress is linked with markers of more advanced disease in patients with chronic lymphocytic leukemia (CLL), the most common form of leukemia among adults.

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The study, recently published in Cancer, sought to correlate stress and disease-specific markers in the blood of patients with CLL. The investigators, from The Ohio State University’s Arthur G. James Cancer Hospital, observed 96 patients with CLL who had relapsed or refractory disease and who were then entering a phase 2 trial of the now-approved ibrutinib, an inhibitor of Bruton’s tyrosine kinase. The patients completed the Impact of Events Scale-Revised survey to assess their stress levels. The survey asked questions about intrusive thoughts, avoidant thoughts or behaviors, and hyperarousal. Possible scores ranged from 0 to 88, with higher numbers corresponding with greater levels stress. The investigators also measured patients’ absolute lymphocyte count (ALC), which is one measure of disease severity in CLL, as well as plasma levels of multiple cytokines.

The investigators found that higher levels of stress predicted higher ALCs (P &thinsp;<&thinsp;.05). Higher stress also predicted higher levels of the inflammatory cytokines tumor necrosis factor alfa (TNF) (P &thinsp;<&thinsp;.05) and interleukin 16 (IL-16) (P&thinsp;<&thinsp;.01). TNF is particularly crucial in CLL, because it increases the proliferation and viability of malignant cells. IL-16 is believed to mediate communications between B cells and T cells within lymph node follicles, and may suppress effector T-cell function.

Stress was also associated with higher levels of chemokine ligand 3 (CCL 3) (P&thinsp; <&thinsp;.05). CCL 3, which the authors of the study say not has not been assessed before in relationship to stress, is of particular note: this cytokine facilitates development of CLL cells in the spleen and lymph nodes.

Even after controlling for older age, male sex, the presence of comorbidities, the number of prior treatments, and deletion of the short arm of chromosome 17—all of which are predictive of poorer outcomes in CLL&mdash;the associations between stress and elevated markers of disease were still apparent.

“All 4 variables we measured are related to prognosis in CLL patients, so they have a lot of relevance,” Barbara L. Andersen, PhD, lead author of the study and professor of psychology at The Ohio State University, said in a statement. “It’s more evidence of the importance of managing stress in cancer patients,” she added.

The investigators say that their data are consistent with the hypothesis that stress is a negative interface to an already weakened immune system, but they add that further data will be needed to help clarify these responses and their relationship to relapse in patients with CLL.

Reference

Andersen BL, Goyal NG, Weiss DM, et al. Cells, cytokines, chemokines, and cancer stress: a biobehavioral study of patients with chronic lymphocytic leukemia. Cancer. 2018 Aug 1;124(15):3240-3248. doi: 10.1002/cncr.31538.