Trial Information

Humoral and Cellular Immune Responses After Influenza Vaccination in Patients With Postcancer Fatigue and in Patients With Chronic Fatigue Syndrome.

Background PCF is a frequently occurring, severe, and invalidating problem in cancer
survivors, impairing quality of life. The prevalence of PCF observed in longitudinal
follow-up studies ranged from 19-39%. Cognitive behavior therapy, especially designed for
PCF, seemed to be an effective treatment option for PCF. However, although it is now
possible to effectively treat PCF, the nature of the underlying physiology of PCF remains
unclear.

Hypotheses about mechanisms explaining cancer-related fatigue have already been described,
including dysregulation of brain serotonin, dysregulation of the
hypothalamic-pituitary-adrenal axis responsiveness, disruption of the circadian rhythm,
alterations in muscle and ATP metabolism, and activation of the vagal afferent nerve.
Furthermore, the presence of an underlying immunological problem has been suggested as an
explanation for PCF.

Another group of patients suffering from severe fatigue symptoms are patients with CFS. The
estimated worldwide prevalence of CFS is 0.4-1%. In the Netherlands, about 100.000 patients
are suffering from chronic fatigue, of which 30.000 to 40.000 suffer from CFS. In contrast
to fatigue in patients with PCF, in patients with CFS no clear precipitating factor could be
identified. Also for patients with CFS, a cognitive behavior therapy is designed, which is
proven to be effective, but the pathophysiological mechanism of CFS remains unclear.

Hypotheses explaining the pathophysiological mechanism of CFS include morphological and
metabolic alterations in the brain, diminished central activation of muscles, altered
central nervous system functioning, a neuroendocrine disturbance, or cognitive impairment.
Furthermore, the presence of an underlying immunological problem has been suggested as an
explanation for CFS.

If an underlying immunological problem is present, PCF and CFS patients might have an
altered response to vaccination.

Aim Therefore, the aim of this study is to compare the humoral and cellular immune responses
upon vaccination, using seasonal influenza vaccination as a model of a vaccination, in PCF
and CFS patients, non-fatigued cancer survivors, and healthy controls.

Research questions

1. Is the humoral and/or cellular immune response after influenza vaccination different
between fatigued patients (PCF and CFS) and non-fatigued individuals?

2. Is the humoral and/or cellular immune response after influenza vaccination different
between PCF and CFS patients? Design The immune responses upon influenza vaccination
will be assessed in 20 PCF patients and in 20 CFS patients. As a control group for PCF
patients, 20 non-fatigued cancer survivors will be included. Additionally, 20 healthy
controls will participate in this study as a control group without a cancer history and
without fatigue symptoms. These four groups will be age- and sex-matched.

At baseline, participants will complete the Checklist Individual Strength, a questionnaire
about the current use of medicines, and a questionnaire about their vaccination history. All
participants will be intramuscularly vaccinated with a single dose of the seasonal influenza
vaccine. Peripheral blood mononuclear cells will be collected at baseline (day 1) and 7 days
after vaccination (day 8), and serum will be collected at baseline and 21 days after
vaccination (day 22). Half a year after vaccination, all participants will be contacted to
check whether a possible infection by influenza had taken place in the meantime or not.

The humoral immune responses on influenza vaccination will measured at day 1 and day 22 in
serum by the haemagglutination-inhibition antibody test. The cellular immune responses will
be measured at day 1 and day 8 by T lymphocyte proliferation, activation, and cytokine
secretion.

Relevance of this study To the best of our knowledge, we are the first to explore both the
humoral and cellular immune responses after influenza vaccination in both PCF and CFS
patients. By means of this study, we would like to improve the understanding of the
underlying physiology of PCF and CFS.