Fatigue Not Linked With Treatment Intensity/Type in Patients With Pediatric Cancer and HSCT

More interventions are needed to address fatigue in survivors of cancer and hematopoietic stem cell transplant.

Pediatric patients with cancer and those who have undergone hematopoietic stem cell transplant (HSCT) may develop long-term effects, including fatigue. However, fatigue is not associated with treatment intensity or therapy type, according to findings published in the Journal of Child Health Care.1

Patients assessed developed severe late effects, were positively associated with parent- and self-report of internalizing and externalizing symptoms, and suffered greater fatigue. When evaluating the social, emotional, behavioral, and physical well-being of survivors of cancer and HSCT, fatigue is an important variable to consider. More interventions are vital in addressing fatigue directly, while also accounting for contributing factors to fatigue and potential negative outcomes that result from fatigue in survivorship.

As part of a larger study which is evaluating the long-term psychosocial functioning of survivors of pediatric cancer, this trial aimed to better understand the specific factors which contribute to fatigue in this patient population, as well as survivors of HSCT. A cross-sectional design was used in the study and patients were recruited from a long-term survivorship clinic at an academic medical center and affiliated pediatric hospital.

“In this sample, increased fatigue was associated with both self- and parent-reported internalized symptomology and externalizing problems. The relationship between increased fatigue and higher reports of internalizing problems is consistent with prior research,” wrote study authors led by Jeffery S. Karst, MD, Department of Pediatrics at the Medical College of Wisconsin.

The study used a cross-sectional design and patients were recruited from a long-term survivorship clinic at an academic medical center and affiliated pediatric hospital. Patients were eligible for enrollment in the trial if they were aged 5 years and older, at least 2 years posttreatment, able to read and write in English, and were being seen for their first visit in the clinic. Caregivers were also eligible if they were able to read and write in English.

A total of 100 patients were enrolled in the trial and 87 of them completed the fatigue measures, thus being included in the analysis. No significant differences were seen in regard to key demographics, including age, race, or sex. There also were no differences in treatment-related variables like treatment duration and treatment intensity.

The final sample of 87 patients was made up of mostly males (54%), a majority of which were Caucasian (87%). At the time of the survivorship clinic visit, the mean age of patients was 13.9 years. The mean age at the time of diagnosis was 7.0 years. Additionally, patients were an average of 4 years, 9 months post-treatment, and the mean treatment duration was 20.5 months.

Of those enrolled, the most common diagnosis for patients was leukemia in 47 patients (54%), then lymphoma in 14 (16%), solid tumor in 8 (9%), bone tumor in 7 (8%), and central nervous system tumor in 6 (7%). Further, 49% of patients had moderately intensive treatment, 28% were very intensive, and 22% had the most intensive treatment. Four of 87 patients (4.6%) made up the overall incidence of clinically significant fatigue in this sample.

Investigators examined the relationship between treatment-related fatigue and time since diagnosis, time since the end of treatment, and overall duration of treatment. Findings revealed that there was a statistically significant and inverse relationship seen between fatigue and time since diagnosis (95% CI, -.57- -.03). This suggested that there was greater disease for those who were more recently diagnosed. Still, a statistically significant relationship between fatigue and time since treatment completion or fatigue and treatment duration was not demonstrated.

There were statistically significant negative correlations also found between internalizing symptoms and treatment-related fatigue on parent reports (95% CI, -.66 - -.05) and also on self-reports (95% CI, -.76 - -.14). For fatigue and late effects, there were also statistically significant and inverse relationships found between treatment-related fatigue and externalized symptoms on both parents (95% CI, -.45 - -.01) and self-report (95% CI, -.54 - -.01).

Differences in fatigue among different levels of treatment intensity were also assessed as 43 patients in the study received moderately intensive treatment, 25 received very intensive treatment, and 19 received most intensive treatment. However, no statistically significant difference was reported among the groups in their reported fatigue.

Additionally, there was no difference in fatigue for the 23 patients who received tumor site radiation (26%) vs the 64 patients who did not (74%). There also were no statistically significant differences found for the 36 patients who received radiation (41%) and for the 51 who did not (59%), for the 60 patients who received alkylating agents (69%), 61 who got anthracyclines (70%), and the 10 who received platinum-based chemotherapy (12%). No significant difference was seen between those who as a part of their treatment had received steroids (62%) or not (38%) regarding treatment-related fatigue.

Further, the number of patients who either had received total body irradiation or cranial spinal radiation was too small for statistical analysis.

Overall, this study which examined patients who had survived pediatric cancer and HSCT showed that this patient population is at risk for many long-term effects, including fatigue, following their treatment. However, this research showed that the 87 patients examined had estimates of clinically significant fatigue which were lower than what has been seen in previous research.

“It is possible that lower estimates were obtained due to a relatively long off-treatment duration as participants were, on average, over 4 and a half years off treatment. Given our finding that fatigue was lower in participants further out from time of diagnosis and treatment completion, it is possible that fatigue is most salient in the intermediate time between the immediate transition off active treatment and long-term survivorship,” wrote the study authors.

Karst JS, Hoag JA, Anderson LJ, Schmidt DJ, Schroedl RL, Bingen KM. Evaluation of fatigue and related factors in survivors of pediatric cancer and hematopoietic stem cell transplant. J Child Health Care. 2022;26(3):383-393. doi:10.1177/13674935211014748