A Multidimensional Approach to Measuring Distress in Children Undergoing Hematopoietic Stem Cell Transplantation: Three Raters’ Perspectives and Stress Biomarkers in Saliva and Blood

Background Hematopoietic stem cell transplantation (HSCT) offers a potentially life-saving cure to adults and children suffering from advanced malignancies or other incurable immunological, hematological, or metabolic diseases. The substantial advances in HSCT-technology during the last 30 years are paralleled by continuously rising numbers of transplantations and improved long-term survival. Despite striking progress, HSCT is still associated with severe physical and psychological distress. While medical aspects of HSCT have received comprehensive scientific attention, there are comparatively few studies examining the psychosocial effects of HSCT in childhood.

Material and Methods We analyzed the type, course and influencing factors of distress during pediatric HSCT by using a multidimensional approach encompassing three raters’ perspectives and stress biomarkers in saliva and blood. The aim of this prospective study was to establish a scientific basis for the development of supportive interventions adjusted to the needs of children undergoing HSCT.

Methods: We examined mental and somatic distress of n=39 children in the assessment period between ten days before and 200 days after HSCT at eight measurement points (baseline; day -10 before stem cell transfusion, day 0 (day of stem cell transfusion), day +10, day +20, day +30, day +60, day +100 and day +200). At each time point distress was measured by questionnaires administered to parents, medical staff, and children as well as through established stress biomarkers in saliva (alpha-amylase) and blood (cortisol, free triiodothyronine, free thyroxine and thyroid-stimulating hormone). Additionally, state and trait anxiety of parents as well as self-efficacy of adolescents were captured by questionnaires at baseline, day +30 and day +200.

Results Particularly adolescents showed already heightened mental distress-levels on admission to hospital. Somatic distress of all children and depressive symptoms of adolescents peaked at the day of stem cell transfusion with a subsequent decline. This trajectory of distress symptoms was not reflected by the course of the stress biomarkers.

While there was high agreement between the ratings of parents and their children regarding all distress assessments, proxy reports by parents and medical staff showed higher consensus regarding physical than psychological distress. Thyroid hormone levels correlated significantly negatively with the distress intensity depicted by questionnaires.

Age, trait anxiety of parents and self-efficacy of adolescents did not yield significant influence on the extent of distress perceived by the children during HSCT. However, we found significant, positive correlations between state anxiety of parents and self-rated mental distress of their adolescent children as well as between state anxiety of parents and somatic and mental distress of their children as rated by the parents. Clinical factors showed little effect on distress intensity in general. Yet children who received an allogeneic HSCT reported significantly stronger feelings of helplessness than children who received an autologous HSCT. Moreover, cortisol levels were significantly higher in children receiving a haploidentical HSCT (compared to children receiving an HSCT from MSD or MUD) and in children with relapse of their disease (compared to children without relapse).

Conclusions An ideal support program should start already prior to HSCT and encompass at least the acute in-patient phase of the transplantation. Furthermore, communication about the psychological distress of children should be actively encouraged in clinical settings and whenever possible the child should be consulted directly. To reevaluate the suitability of biomarkers as distress indicators during HSCT as well as the influence of age, trait anxiety of parents and self-efficacy of adolescents on distress during HSCT additional studies with bigger cohorts are necessary. We suggest testing the effect of psychotherapy for children and their families before and during the acute phase of HSCT in randomized controlled intervention studies to further improve future HSCT care.

No relevant conflicts of interest to declare.