Stress Linked with Biomarkers of Poor Prognosis in CLL

Stress may affect certain cellular, cytokine, and chemokine markers in the body that have been associated with progressive disease in patients with chronic lymphocytic leukemia (CLL), according to the results of a study published in Cancer.

“Although previous research has examined stress associations in animal models, to our knowledge, this is the first biobehavioral study to demonstrate that stress covaries with four key biomarkers in patients with CLL,” wrote Barbara L. Andersen, PhD, of The Ohio State University, and colleagues. “The current data are consistent with the hypothesis that stress may be a negative interface to an already weakened immune system.”

With their study, Andersen and colleagues wanted to examine how stress interacts with the immune system of patients with CLL, and whether it correlates with any disease-specific, negative prognostic markers.

The observational study included 96 patients with relapsed/refractory CLL who were entering a phase II trial of ibrutinib. Prior to receiving the study drug, the patients completed a validated self-report measure of stress and had blood work drawn for absolute lymphocyte counts (ALCs), and for cytokine and chemokine enzyme-linked immunosorbent assays.

Controlling for variables including comorbidities, stress was a significant predictor of higher ALC (P = .037), considered to be a “salient marker of CLL burden.” In addition, stress was associated with tumor necrosis factor alpha (TNFα) (P = .016).

“The association between stress and TNFα is particularly important in CLL, because malignant cells release TNFα spontaneously, and TNFα increases their proliferation and viability,” the researchers wrote. “The current TNFα finding adds to the biobehavioral cancer literature, because most studies have reported that depression, rather than stress, is related to higher levels of TNFα. Stress and depression can co-occur in patients, and future research may examine the independent and synergistic effects of depression and stress on inflammatory markers like TNFα.”

Finally, stress was also linked with higher levels of interleukin 16 (P < .001), and chemokine ligand 3 (P = .027). No association was found between stress and a proliferation‐inducing ligand, B‐cell activating factor, IL-6, IL-10 or vascular endothelial growth factor.

“Patients with moderate-to-severe stress, anxiety, and/or depressive symptoms are in need of early, evidence-based, psychological treatment to address current difficulties and lower the likelihood of poorer quality of life, which otherwise may follow,” the researchers wrote.