Application of the National Comprehensive Cancer Network-distress thermometer in pediatric patients during autologous and allogeneic hematopoietic stem cell transplantation and relationship to blood parameters of the stress axis.

PURPOSE: Hematopoietic stem cell transplantations (HSCT) are extremely stressful procedures for pediatric patients. The activation of the hypothalamic pituitary adrenocortical axis (HPA) can influence the immune system negatively and therefore the overall outcome. The distress thermometer (DT) is an easy to use tool for the self-assessment of perceived distress. METHODS: In this prospective study, a DT with an attached problem list was used in 40 pediatric patients undergoing HSCT and in one parent of each patient. The patients were aged 10-18 years. The patients' cortisol, thyroid stimulating hormone, free triiodothyronine and thyroxine levels were measured regularly during the in-patient stay. RESULTS: After admission to the hospital, the stress levels of the pediatric patients and their parents increased and reached their maximum on the day of HSCT. The overall stress values of the parents were higher than those of their children. There was a significant difference in the parents' stress levels on the day of HSCT, as compared to their stress levels on other days. The mean cortisol values of the pediatric patients also increased after admission, reaching significant elevated levels above the upper normal limit 1 week after HSCT and on discharge day. Although the pediatric patients experienced mainly exhaustion, especially on the day of transplantation, their parents mainly felt worry and anxiety. Interestingly, the rate of worry among children increased in the post-transplant period and reached its maximum on the day of discharge. CONCLUSIONS: In summary, a significantly increased stress level is shown for both the patients and their parents. This is reflected for the patients both in the DT scores and in the increased cortisol values. For the parents, the focus is primarily on worry and anxiety, for the patients primarily on exhaustion and worry.

Screening for distress and quality of life in pediatric patients after allogeneic or autologous hematopoietic stem cell transplantation using a self-reporting instrument, blood stress biomarkers and an expert rating scale (PO-Bado).

OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) is highly distressing and potentially traumatizing for pediatric and young adult patients (PYAP). At present, there is little evidence on their individual burdens. METHODS: In this prospective cohort study, the course of the psychological and somatic distress was investigated on eight observation days (day -8/-12, -5, 0 (day of HSCT), +10, +20, and + 30 before/after HSCT), using the PO-Bado external rating scale and the EORTC-QLQ-C15-PAL self-assessment questionnaire. Stress-associated blood parameters were determined and correlated with the results of the questionnaires. RESULTS: A total of 64 PYAP with a median age of 9.1 years (range 0-26 years) who underwent autologous (n = 20; 31%; autoHSCT) or allogeneic (n = 44; 69%; alloHSCT) HSCT were analyzed. Both were associated with a significant reduction in QOL. The reduction in self-assessed QOL correlated with somatic and psychological distress as assessed by medical staff. While somatic distress was similar in both groups with a maximum around day+10 (alloHSCT 8.9 ± 2.4 vs. autoHSCT 9.1 ± 2.6; p = 0.69), a significantly higher level of psychological distress was seen during alloHSCT (e.g. day0 alloHSCT 5.3 ± 2.6 vs. day0 autoHSCT 3.2 ± 1.0; p < 0.0001). CONCLUSIONS: The maximum of psychological and somatic distress, as well as the lowest quality of life, ranges between day 0 and + 10 after both allogeneic and autologous pediatric HSCT. While somatic distress is similar during autologous and allogeneic HSCT, the allogeneic group seems to be affected by higher psychological distress. Larger prospective studies are needed to evaluate this observation.

Efficacy, Safety And Feasibility Of Antiemetic Prophylaxis With Fosaprepitant, Granisetron And Dexamethasone In Pediatric Patients With Hemato-Oncological Malignancies.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic prophylaxis with corticosteroids, 5-HT3R-antagonists and NK1R-antagonists. The NK1R-antagonist fosaprepitant has shown favorable results in pediatric and adult patients. There is little pediatric experience with fosaprepitant. METHODS: This non-interventional observation study analyzed 303 chemotherapy courses administered to 83 pediatric patients with a median age of 9 years (2-17 years), who received antiemetic prophylaxis either with fosaprepitant and granisetron with or without dexamethasone (fosaprepitant group/FG; n=41), or granisetron with or without dexamethasone (control group/CG; n=42), during moderately (CINV risk 30-90%) or highly (CINV risk>90%) emetogenic chemotherapy. The two groups' results were compared with respect to the safety and efficacy of the antiemetic prophylaxis during the acute (0-24hrs after chemotherapy), delayed (>24-120hrs after chemotherapy) and both CINV phases. Laboratory and clinical adverse events were compared between the two cohorts. RESULTS: Adverse events were not significantly different in the two groups (p>0.05). Significantly fewer vomiting events occurred during antiemetic prophylaxis with fosaprepitant in the acute (23 vs 142 events; p<0.0001) and the delayed (71 vs 255 events; p<0.0001) CINV phase. In the control group, the percentage of chemotherapy courses with vomiting was significantly higher during the acute (24%/FG vs 45%/CG; p<0.0001) and delayed CINV phase (28%/FG vs 47%/CG; p=0.0004). Dimenhydrinate (rescue medication) was administered significantly more often in the CG, compared to the FG (114/FG vs 320/CG doses; p<0.0001). Likewise, in the control group, dimenhydrinate was administered in significantly more (p<0.0001) chemotherapy courses during the acute and delayed CINV phases (79 of 150; 52.7%), compared to the fosaprepitant group (45 of 153; 29.4%). CONCLUSION: Antiemetic prophylaxis with fosaprepitant and granisetron with or without dexamethasone was well tolerated, safe and effective in pediatric patients. However, larger prospective trials are needed to evaluate these findings.

Comparison of procalcitonin and C-reactive protein as early diagnostic marker for the identification of transplant-related adverse events after allogeneic hematopoietic stem cell transplantation in pediatric patients.

PURPOSE: To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4-17.8 years) undergoing allogeneic HSCT with respect to major TRAE. RESULTS: 26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1-4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001). CONCLUSIONS: CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.