Severe, persistent fatigue common in Hodgkin lymphoma survivors

Severe acute and persistent fatigue appeared common among survivors of Hodgkin lymphoma, regardless of their tumor stage or treatment, according to results from a longitudinal study.

Survivors of Hodgkin lymphoma have reported cancer-related fatigue as a common impairment after treatment. Further, data have suggested levels of fatigue are high and remain raised even years after treatment.

“This finding is of special interest in patients with Hodgkin lymphoma because the disease has become a curable cancer for most patients,” Stephanie Kreissl, MD, of the department of internal medicine at the University Hospital of Cologne in Germany, and colleagues wrote.

“The median age at first diagnosis is about 30 years and improved curability of the disease results in a continuously growing number of Hodgkin lymphoma survivors at risk for long-term sequelae and impairment of their health-related quality of life.”

Still, “detailed and reliable” data on cancer-related fatigue are limited, researchers wrote.

“A better understanding of fatigue in patients with Hodgkin lymphoma and survivors could facilitate the acceptance of this health problem as a discrete diagnosis and might help patients and physicians to develop intervention strategies,” they added.

Kreissl and colleagues analyzed data from 4,215 patients with a valid fatigue assessment from diagnosis through 5 years after treatment. Patients were enrolled in three first-line clinical trials conducted by the German Hodgkin Study Group — the HD13 trial for early-stage favorable disease (n = 881), the HD14 trial for early-stage unfavorable disease (n = 1,588), and the HD15 trial for advanced-stage disease (n = 1,746).

Researchers used the fatigue scale of the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire.

Patients with advanced-stage disease at diagnosis reported the highest baseline mean fatigue scores (49) compared with those with early stage unfavorable (39.8) and early-stage favorable (30.8) Hodgkin lymphoma.

In addition, the proportion of patients with severe fatigue scores increased with advanced stages of disease — 48% of patients in the HD15 trial reported fatigue scores of 50 or more, compared with 37% of patients on the HD14 trial and 24% of patients on the HD13 trial.

In the second year following the end of treatment, fatigue scores were 28.5 in the HD13 trial, 28.8 in the HD14 trial and 30.7 in the HD15 trial. In the fifth year after treatment, fatigue scores were 30.8 in HD13, 27.1 in HD14 and 28.2 in HD15.

Predictors of fatigue in the second and fifth year after end of treatment included baseline fatigue and age as a continuous variable (P < .001 for both).

“It is important to note that persistent severe fatigue is a disabling disease, and has a major impact on patients’ lives,” the researchers wrote. “These findings support the importance of baseline fatigue as a precursor of long-term fatigue.”

Patients from all three trials reported increases in fatigue scores after beginning systemic chemotherapy treatment; however, scores were almost identical across all disease stages and treatments.

“Surprisingly, the large effect of disease stage on the extent of baseline fatigue did not translate into different fatigue levels during treatment, because all the different treatment intensities used in our trials induced very severe fatigue symptoms,” Kreissl and colleagues wrote.

Researchers noted that patient sex and Hodgkin lymphoma-specific risk factors at baseline did not consistently predict fatigue in the first, second, and fifth year after the end of treatment.

The researchers acknowledged that because the clinical trial setting focused on Hodgkin lymphoma–specific outcome parameters, they were unable to evaluate relevant comorbidities such as depression, anxiety and sleep disorders. Further, the number of missing variables increased during follow-up.

“Cancer-related fatigue is a distinct diagnosis and a potentially disabling disease that has a course different from that of the coexisting diagnosis of Hodgkin lymphoma; successful treatment of the malignant lymphoma does not prevent the development of severe persistent fatigue,” Kreissl and colleagues wrote.

Psychological factors — including susceptibility to anxiety or depression — or biological factors, such as immunocompetence or heritable genetic variations, may play a role in cancer-related fatigue, Michael Henry-Amar, MD, PhD, and Raphaël Busson, MD, from the Centre de Traitement des Données du Cancéropôle Nord-Ouest, wrote in an accompanying editorial.

“Before tertiary prevention interventions are undertaken to manage or prevent the development of persistent fatigue, among which exercise programs and cognitive behavioral therapy have been proposed, there is a need to understand the mechanisms by which individuals who develop a cancer are also susceptible to develop abnormal fatigue,” Henry-Amar and Busson wrote. – by Kristie L. Kahl

Disclosure: The researchers, Henry-Amar and Busson report no relevant financial disclosures.