High Prevalence of Chronic Fatigue in Long Term Survivors of Childhood Acute Lymphoblastic Leukemia and Lymphoma

Chronic fatigue is a frequent and distressing late effect after successful cancer treatment. However, few studies have included survivors of childhood cancers.

The primary aim of the study was to assess the prevalence of fatigue in long-term survivors of childhood acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), and to compare with the Norwegian general population. A secondary aim was to explore the association between cardiac or pulmonary late effects and fatigue in long-term survivors after NHL and HL.

This population-based cross-sectional study included tumor-free adult survivors of childhood ALL, NHL and HL diagnosed between 1970 and 2002 at an age of <19 years with at least 5 years follow-up time. The enrolled patients underwent extensive biochemical and clinical investigation including echocardiography and estimation of lung volumes and diffusion capacity. Clinical information was retrieved from the patient records. Chalder′s fatigue questionnaire (FQ) was used to assess fatigue. Chronic fatigue (CF) was defined as a substantially increased level of fatigue with duration of more than 6 months. 1423 age and gender matched individuals from the general Norwegian population served as controls.

A total of 290 patients completed the questionnaire (ALL 151, NHL 47, HL 92). Median age (range) at assessment was 29.9 (18.3–54.5) years. Median follow-up time from diagnosis was 21.3 (6.9–39.2) years. The overall prevalence of CF was 27% (ALL 23%, NHL 30%, HL 34%), as compared to 8.4% among the controls (p>0.001). There was a tendency towards a higher prevalence of CF by increasing age (32% among subjects aged ≥30 years at follow-up vs. 22% in subjects aged<30 years, p=0.063). This was most pronounced among the ALL survivors (36% among subjects aged ≥30 years years at follow-up vs. 13% among subjects aged <30 years, p=0.001). In ALL survivors, older age at diagnosis was associated with higher prevalence of CF (15% among subjects aged <6 years at diagnosis vs. 32% among subjects aged ≥6 years, p= 0.012). Indeed, among all survivors ≥6 years at diagnosis, the ALL group had a similar prevalence of CF as the two other diagnostic groups; 32%. No association was found between CF and gender, time from diagnosis, radiotherapy, cumulative anthracycline dose, body mass index, proBNP or hypothyreosis. Among the lymphoma survivors the presence of B-symptoms at diagnosis tended to be associated with CF (Presence: CF 48% vs. Absence: CF 29%, p=0.058). In long-term survivors of NHL and HL, no association was found between CF and aortic valve disease, total lung capacity and diffusion capacity.

Compared to the general population the prevalence of CF is 3-fold increased in long-term survivors of childhood leukemia and lymphoma. The prevalence is highest in HL (34%), but, rather surprisingly, even ALL survivors have a high occurrence of CF (23%). The lack of association between CF and somatic co-morbidity or dysfunction warrants future studies exploring the etiology of CF in long-term survivors.

No relevant conflicts of interest to declare.