To our knowledge, this is the first study to assess HRQoL in children with CML-CP and explore the associated variables. Although those children mainly received oral TKIs, which were different from other cancer patients requiring intensive chemotherapy in hospital, we found some variables, including female gender and age, were associated with HRQoL. This is consistent with the previous studies about HRQoL of children with other cancers[4, 6, 8, 10–12, 14]. Just as adult CML, TKI-related symptoms reported was the variables correlated with impaired HRQoL. In addition, We found that the lower the mother's education level, the worse HRQoL the children had, and parents reported more gastrointestinal disorders and worries about the future and less concerns about the appearance than children’s reports.
Our study showed that female children felt more unsatisfied with their appearance, and had worse HRQoL than males, which was consistent with previous findings in other studies[4, 6, 11]. On the other hand, we found that male, especially living in the village, experienced worse pain, which could be attributed to the more physical activity of male. The discomfort after exercise, coupled with the side effects of TKI drugs, may cause them to experience worse musculoskeletal pain; however, further research on this phenomenon would be recommended.
Age at diagnosis was related to the HRQoL of childhood cancer survivors, but the results are different. Speechley et. al. found that the older the children at diagnosis, the lower were physical and psychological scores of survivors. Fradell’s study showed that HRQoL of survivors with acute lymphoblastic leukemia at older age was worse, while Alessi reported that HRQoL of survivors with malignant tumors at older age was better than those diagnosed at a younger age. In our study, the age at diagnosis was associated with perceived physical appearance; that is, children who were older at diagnosis were more likely to be dissatisfied with their appearance, who often complained about the skin rash and edema, and they had worse HRQoL. In addition, the younger age of the children at study was associated with the worse HRQoL, which was mainly manifested for procedural anxiety and cognitive problems. It is easy to understand that the frequent hospital visits and the need for invasive procedures (such as blood tests every month in the first 3 months and every 3 months after that, and bone marrow puncture every 3 months before CCyR) may make the younger children feel scared. Moreover, younger children may experience more difficulties in cognitive problems, as Hardy and coworkers reported in their study. The reasons might be that - although not recommended by medical guidelines - parents of younger children restrict the children’s school activities, at least in flu season, to reduce the infectious risk caused by the physical immunity of TKI-therapy. Therefore, younger children were frequently absent from school, which might lead to cognitive problems. Relatively older children might be less detached from school, due to the ability to protect themselves in school and study pressure.
In our study, we found that mother’s educational levels also impact their children’s HRQoL. Lower educational qualification of mothers was associated with worse HRQoL of their children. This phenomenon may be related to the mother’s role in the family[27, 28]. In China, a mother is more responsible for taking care of the family at home and have a closer relationship with their children, resulting that their feeling could affect children’s HRQoL. Mothers with lower education level may have a certain level of cognition whose children are diagnosed with CML, but not comprehensive understanding. Females are delicate, sensitive, and emotional, which usually leads to over-protective behavior. These behaviors of females, in turn, affects their children’s HRQoL, especially in the aspects of pain, worry, and self-appearance evaluation.
Many studies found that fatigue was the most common adverse effect in adults with CML receiving TKI-therapy, and fatigue was also the main reason for the worse HRQoL in adult patients[21, 30–34]. In our study, the first two most common adverse effects reported were gastrointestinal disorders and skeletal muscle pain. These adverse reactions may affect nutrition and sleep quality, thus resulting in fatigue and lack of energy to participate in physical activities[11, 35]. Furthermore, the children complaining a discomfort of TKI-therapy reported dissatisfaction with appearance, and impaired communication problems. This finding can be explained by the experience of pain, nausea and fatigue, which impaired their ability to fully participate in physical and social activities[15, 34, 36]. Moreover, the change in body image caused by TKI-therapy, such as weight gain, skin rash, or skin color, causes children to develop inferiority and then refuse to socialize. Through these aspects, discomfort reported would affect the HRQoL of children with CML.
Our assessment of HRQoL was mainly based on parent proxy-report, but strong agreement existed between children self-report and parent proxy-report scores on the eight dimensions and total score, so the potential bias between children self-report and parent proxy-report in the results was not likely to be a problem in our study. Parent proxy-report had become an adequate substitute for child self-report, even though large differences can exist in the dimension of nausea, worry, and perceived physical appearance. The difference between child self-report and parent proxy-report reflected the different perspectives of children and parents about the children’s HRQoL, consistent with Belson’s finding. Parents reported worse HRQoL than their children in the aspects of gastrointestinal disorders and worried about the future, whereas children reported more significant self-negation of appearance. Parents’ view about children’s nausea and poor diet may be related to their burden of care-giving and their own well-being. Moreover, this is communicated with Chinese traditional culture, where parents tend to make diet culture a priority, and exaggerate their children’s low appetite. Rama Zilber and Vlachioti defined the difference of opinion of worry and reported that the basic concern of all parents was the health and future of their children[17, 23]. They considered disease to have more negative consequences than children themselves. The life experiences and inner lives of children were different from those of the adults, and they may pay more attention to their present conditions and feelings, like appearance, caused by skin rash, change of skin color, short stature produced by TKI-therapy. However, some parents usually have less communication with their children and ignore their children’s psychological sensation.
Our study has some limitations. First, respondents needed to be old enough to complete the self-report part independently, and some parents refused their children’s wish to answer the questionnaire because of privacy concerns, which significantly reduced the number of child self-report subjects. Second, the patients’ self-reported discomfort and degree were subjective feelings with individual differences. Third, parents usually pay different attention to the child’s growth, and the mother is more delicate in the relationship, but we did not restrict the selection of father and mother in answering the parent proxy-report.
In conclusion, our findings reflected the HRQoL of children with CML and showed that female gender, increasing age at diagnosis, younger age at study, low mother’s educational qualification, and TKI-related symptoms had a negative effect on their HRQoL. In addition, parents paid more attention to poor diet and worried about the future, while children with CML were more dissatisfied with their appearance. This requires pediatrician not only to provide patients with the most appropriate suitable treatment, but also to pay more attention to the patients' psychological and physical needs.