Feature

Stress linked to poor outcomes in chronic lymphocytic leukemia

Barbara L. Andersen, PhD
Barbara L. Andersen

Stress appeared associated with immune and inflammatory processes that contribute to cancer cell proliferation and survival among patients with relapsed or refractory chronic lymphocytic leukemia, according to study findings published in Cancer.

“All four variables we measured are related to prognosis in [patients with] chronic lymphocytic leukemia, so they have significant relevance,” Barbara L. Andersen, PhD, professor of psychology at The Ohio State University and director of the cancer prevention and control program at the university’s comprehensive cancer center, said in a press release. “This study adds to evidence for the importance of managing stress in [patients with] cancer.”

The investigators examined the association between stress and diseasespecific, negative-prognostic cellular, cytokine and chemokine markers among 96 patients with relapsed or refractory CLL.

Results showed increased levels of stress were associated with increased levels of circulating cancerous cells, cytokines tumor necrosis factor-alpha and interleukin-16, and the chemokine CCL3. These associations persisted after researchers controlled for other factors, including sex, number of prior treatments and presence of deletion 17p.

“The fact that stress shows an effect on CLL even after we controlled for other factors suggests it may be relevant to the course of CLL,” Andersen said.

Andersen spoke with HemOnc Today about the significance of the study and the implications of the findings.

Question: Can you explain the rationale for the study?

Answer: The rationale is based on decades of evidence that supports our biobehavioral model of cancer stress and disease course. In that model, patients experience psychological stress, which can be elevated by a cancer diagnosis or treatment. This stress has biologic effects that confer worsened immune system functioning, which can result in adverse health outcomes. My colleagues in the Stress and Immunity Cancer Projects laboratory and I have conducted decades of research that shows stress impacts immune processes and disease outcomes among patients with breast cancer. Given this evidence, we believed that stress effects could be observed among patients with CLL — a cancer that directly impacts the immune system.

Q: How did you conduct the study?

A: We gathered data from a nonrandomized phase 2 monotherapy study of ibrutinib (Imbruvica; Pharmacyclics, Janssen). The primary goal was to determine 2-year PFS among patients with relapsed or refractory CLL who were receiving ibrutinib. We used cytokine and chemokine assays that allowed us to examine whether stress was related to biological markers shown to be associated with relapse or progression in CLL.

Q: What did you find?

A: Higher levels of psychological stress predicted higher levels of absolute lymphocyte counts, tumor necrosis factor-alpha, interleukin-16 and CCL3 on day 1 of treatment with ibrutinib. Absolute lymphocyte count numbers are used, along with other variables, to establish diagnosis and track disease progression. Tumor necrosis factor-alpha and interleukin-16 are proinflammatory cytokines that support CLL proliferation and survival. CCL3 is a chemokine that supports malignant cell signaling that has been shown to be associated with advanced disease. Statistical analyses controlled for other important variables, including age, sex, comorbidities and number of prior treatments, as well as behavioral correlates of inflammation, including BMI and smoking status. We observed no relationship between stress and other cytokines and chemokines measured, including A proliferation-inducing ligand, B-cell activating factor, interleukin-6, interleukin-10 or vascular endothelial growth factor.

Q: What are the implications of the findings ?

A: Understanding the association between stress and immune factors is needed due to the importance of these immune factors in the destruction of malignant cells and surveillance against re-emergence of cancer. With these findings, we hope to convey that stress is not only an issue of emotional disruption. Ideally, our findings will provide an impetus for early, evidence-based, psychological interventions for patients who experience moderate to severe stress.

Q: What are the most appropriate strategies members of the clinical community can e mploy to manage patient stress?

A: Patients have to be assessed to determine whether they are experiencing stress. At the very least, patients should be assessed at diagnosis, before, during and after any treatment or treatment change. ASCO guidelines have recommended screening as well as specific measures of anxiety and depressive symptoms to use. The immediate goal is to identify which patients are experiencing moderate to severe levels of stress, as data show those individuals will have more severe symptoms, slower recovery and impaired health-related quality of life. Screening is only a first step. The key effort is referring patients for, or providing them with, evidenced-based treatments for anxiety and depressive disorders.

Q: What are next steps for research?

A: This is an important early study, providing the need for replication and extensions. It is unknown if these stress/immune relationships extend in time as treatment is received or if these effects play any role in duration of disease improvements or relapse. – by Jennifer Southall

Reference:

Andersen BL, et al. Cancer. 2018;doi:10.1002/cncr.31538.

For more information:

Barbara L. Andersen, PhD, can be reached at The Ohio State University, 1835 Neil Ave., Columbus, OH 43210; email: andersen.1@osu.edu.

Disclosure: Andersen reports no relevant financial disclosures.

Barbara L. Andersen, PhD
Barbara L. Andersen

Stress appeared associated with immune and inflammatory processes that contribute to cancer cell proliferation and survival among patients with relapsed or refractory chronic lymphocytic leukemia, according to study findings published in Cancer.

“All four variables we measured are related to prognosis in [patients with] chronic lymphocytic leukemia, so they have significant relevance,” Barbara L. Andersen, PhD, professor of psychology at The Ohio State University and director of the cancer prevention and control program at the university’s comprehensive cancer center, said in a press release. “This study adds to evidence for the importance of managing stress in [patients with] cancer.”

The investigators examined the association between stress and diseasespecific, negative-prognostic cellular, cytokine and chemokine markers among 96 patients with relapsed or refractory CLL.

Results showed increased levels of stress were associated with increased levels of circulating cancerous cells, cytokines tumor necrosis factor-alpha and interleukin-16, and the chemokine CCL3. These associations persisted after researchers controlled for other factors, including sex, number of prior treatments and presence of deletion 17p.

“The fact that stress shows an effect on CLL even after we controlled for other factors suggests it may be relevant to the course of CLL,” Andersen said.

Andersen spoke with HemOnc Today about the significance of the study and the implications of the findings.

Question: Can you explain the rationale for the study?

Answer: The rationale is based on decades of evidence that supports our biobehavioral model of cancer stress and disease course. In that model, patients experience psychological stress, which can be elevated by a cancer diagnosis or treatment. This stress has biologic effects that confer worsened immune system functioning, which can result in adverse health outcomes. My colleagues in the Stress and Immunity Cancer Projects laboratory and I have conducted decades of research that shows stress impacts immune processes and disease outcomes among patients with breast cancer. Given this evidence, we believed that stress effects could be observed among patients with CLL — a cancer that directly impacts the immune system.

Q: How did you conduct the study?

A: We gathered data from a nonrandomized phase 2 monotherapy study of ibrutinib (Imbruvica; Pharmacyclics, Janssen). The primary goal was to determine 2-year PFS among patients with relapsed or refractory CLL who were receiving ibrutinib. We used cytokine and chemokine assays that allowed us to examine whether stress was related to biological markers shown to be associated with relapse or progression in CLL.

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Q: What did you find?

A: Higher levels of psychological stress predicted higher levels of absolute lymphocyte counts, tumor necrosis factor-alpha, interleukin-16 and CCL3 on day 1 of treatment with ibrutinib. Absolute lymphocyte count numbers are used, along with other variables, to establish diagnosis and track disease progression. Tumor necrosis factor-alpha and interleukin-16 are proinflammatory cytokines that support CLL proliferation and survival. CCL3 is a chemokine that supports malignant cell signaling that has been shown to be associated with advanced disease. Statistical analyses controlled for other important variables, including age, sex, comorbidities and number of prior treatments, as well as behavioral correlates of inflammation, including BMI and smoking status. We observed no relationship between stress and other cytokines and chemokines measured, including A proliferation-inducing ligand, B-cell activating factor, interleukin-6, interleukin-10 or vascular endothelial growth factor.

Q: What are the implications of the findings ?

A: Understanding the association between stress and immune factors is needed due to the importance of these immune factors in the destruction of malignant cells and surveillance against re-emergence of cancer. With these findings, we hope to convey that stress is not only an issue of emotional disruption. Ideally, our findings will provide an impetus for early, evidence-based, psychological interventions for patients who experience moderate to severe stress.

Q: What are the most appropriate strategies members of the clinical community can e mploy to manage patient stress?

A: Patients have to be assessed to determine whether they are experiencing stress. At the very least, patients should be assessed at diagnosis, before, during and after any treatment or treatment change. ASCO guidelines have recommended screening as well as specific measures of anxiety and depressive symptoms to use. The immediate goal is to identify which patients are experiencing moderate to severe levels of stress, as data show those individuals will have more severe symptoms, slower recovery and impaired health-related quality of life. Screening is only a first step. The key effort is referring patients for, or providing them with, evidenced-based treatments for anxiety and depressive disorders.

Q: What are next steps for research?

A: This is an important early study, providing the need for replication and extensions. It is unknown if these stress/immune relationships extend in time as treatment is received or if these effects play any role in duration of disease improvements or relapse. – by Jennifer Southall

Reference:

Andersen BL, et al. Cancer. 2018;doi:10.1002/cncr.31538.

For more information:

Barbara L. Andersen, PhD, can be reached at The Ohio State University, 1835 Neil Ave., Columbus, OH 43210; email: andersen.1@osu.edu.

Disclosure: Andersen reports no relevant financial disclosures.