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-HT 3 R-antagonists and NK 1 R-antagonists. The NK 1 R-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.
1. Background Chemotherapy-induced nausea and vomiting (CINV) is a feared and burdensome complication after emetogenic chemotherapy (EC), especially in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Antiemetic prophylaxis (AEP) is thus a substantial factor in the transplantation management. Guidelines recommend a comprehensive AEP with NK1R-antagonists (neurokinin-1 receptor), 5-HT3R-antagonists (5-hydroxytryptamine-3 receptor), and corticosteroids. The water-soluble aprepitant derivative fosaprepitant (NK1R-antagonist) was shown to be highly effective in adult patients with moderately to highly EC when combined with granisetron (5-HT3R-antagonist). There is very little experience with fosaprepitant in pediatric patients. 2. Patients and Methods In this single-center retrospective study, 80 pediatric patients during allogeneic HSCT who received AEP either with intravenous fosaprepitant and granisetron (fosaprepitant group; FG) or a standard prophylaxis regimen with granisetron two times per day(historical control group; CG) were analyzed for safety and efficacy of the prophylaxis regimen. Efficacy of the two AEP regimen was evaluated comparing the vomiting frequency, percentages of patients vomiting and the need for rescue medication (dimenhydrinate) during the acute (<24h) and the delayed (24-120h) CINV phase in both groups. Safety was evaluated comparing drug-related clinical and laboratory-chemical side-effects (exanthema, gastrointestinal symptoms, sweating, liver and kidney parameters, and electrolytes). Exclusion criteria were vomiting or receiving antiemetic medication within 48 hours before the start of antiemetic prophylaxis. 3. Results A total of 80 pediatric patients with a median age of 9 years (range 2-17 years) who underwent allogeneic HSCT between 2015 and 2018 were consecutively enrolled and analyzed. Patients were transplanted for the treatment of acute leukemia (acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), ALL-relapse, AML-relapse; total: 36.5% of the patients), myelodysplastic syndromes (4.8% of the patients) solid tumors and lymphoma (neuroblastoma, brain tumor, non-Hodgkin's lymphoma, Hodgkin's lymphoma; 44.9% of the patients), and non-malignant hematopoietic diseases (thalassemia major, sickle cell anemia; 13.8% of the patients). The patients received allogeneic grafts from matched unrelated donors (48.4%), matched family donors (16.2%) and mismatched family donors (35.5%). Distribution of the patient characteristics was not significantly different in both study groups (p>0.05). The patients of the FG (n=40; HSCT between 2017 and 2018) received a single dose of fosaprepitant (3.5-4 mg per kg bodyweight (mg/kg); maximum 150 mg; intravenous (IV) infusion) directly before starting the myeloablative conditioning and as PRN (pro re nata) medication every five days after HSCT (same dosage; IV infusion), as well as granisetron (2x20 µg/kg per day; starting on the first day of the conditioning; max. 3 mg; IV infusion <30 min.). The patients of the historical CG (n=40; patients transplanted between 2013 and 2014) received granisetron only at the same dosages. Discontinuation of the antiemetic medication was not necessary for any of the patients (CG and FG). Clinical side-effects and laboratory-chemical changes were not significantly different in both study groups (p>0.05). When compared to the patients of the CG, significantly less patients of the FG experienced vomiting in both, the acute (p<0.001) and the delayed CINV phase (p<0.0001); accordingly, significantly less vomiting events (p<0.0001) were observed during both CINV phases in the FG. Furthermore, the FG received significantly fewer doses of dimenhydrinate in comparison to the CG (p<0.001). 4. Conclusions The prophylaxis regimen with fosaprepitant in combination with granisetron was safe and more effective in comparison to the standard prophylaxis regimen with granisetron only in pediatric patients undergoing allogeneic HSCT with a myeloablative conditioning. However, larger prospective trials are needed to evaluate these findings. 5. Keywords Chemotherapy-induced nausea and vomiting; antiemetic prophylaxis; fosaprepitant; pediatric patients 6. Acknowledgments This study was supported by the Stefan-Morsch-Stiftung, Birkenfeld, Germany. Disclosures Schlegel: Miltenyi Biotec: Patents & Royalties, Research Funding. Seitz:Miltenyi Biotec: Patents & Royalties, Research Funding. Lang:Miltenyi Biotec: Patents & Royalties, Research Funding. Handgretinger:Miltenyi Biotec: Patents & Royalties: Co-patent holder of TcR alpha/beta depletion technologies, Research Funding.
Background: Leukemia in children has a good prognosis with an overall cure rate of 85% in pediatric patients with acute lymphoblastic leukemia and 50-60% in pediatric patients with acute myeloid leukemia. Nevertheless in patients with refractory or relapsed leukemia the prognosis is limited and can only be cured by a salvage chemotherapy, in most cases followed by an allogeneic hematopoietic stem cell transplantation. Methods: In this retrospective case cohort ananlysis we investigated the outcome of eight patients with relapsed or refractory acute myeloid (n=2), lymphoblastic (n=4), biphenotypic (n=1) leukemia or T-lymphoblastic lymphoma (n=1) who failed to respond to standard salvage regimens. They received a salvage therapy with melphalan and cytarabine at our institution between 2015 and 2019. Results: After salvage chemotherapy with melphalan and cytarabine 63% of the patients achieved a remission of the disease and qualified for subsequent allogeneic hematopoietic stem cell transplantation. The one year overall survival rate was 50%, the three year overall survival rate was 29%. 25% of patients experienced a temporary period of fever and SIRS. Conclusions: The reported results of our case cohort analysis indicate that a salvage therapy with melphalan and cytarabine in relapsed or refractory leukemia could represent a curative approach with the possibility of achieving remission and subsequent allogeneic hematopoietic stem cell transplantation. Future multicentre studies are needed to verify the here presented results.
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. A screening instrument should be established to detect elevated stress levels. Methods In this prospective study, a distress thermometer with attached problem list was used in 40 pediatric patients and their parents. The patients were aged 10 to 18 years and received a HSCT. Furthermore, the patients' cortisol, thyroid stimulating hormone, free triiodothyronine and Thyroxine levels were measured regularly during the inpatient 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 the children, with a significant difference on the day of HSCT. The mean cortisol values of the pediatric patients also increased after admission, reaching significant elevated levels above the upper norm limit one week after HSCT and on discharge day. While 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 posttransplant period and reached its maximum on the day of discharge. Conclusions These results confirm the need for early and continuous psycho-oncological intervention with the pediatric patients and their parents, especially up to the day of HSCT.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.