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Antiemetic prophylaxis with fosaprepitant and granisetron in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

ABSTRACT: BACKGROUND:Chemotherapy-induced nausea and vomiting (CINV) is a severe and distressing complication during allogeneic hematopoietic stem cell transplantation (alloHSCT). The antiemetic fosaprepitant has shown favorable results in pediatric and adult patients receiving chemotherapy. Data on fosaprepitant in children and adolescents undergoing alloHSCT are missing. METHODS:In this non-interventional observation study, 120 children and adolescents with a median age of 11.8 years undergoing alloHSCT after a moderately or highly emetogenic conditioning (MEC or HEC) were analyzed. They received an antiemetic prophylaxis with granisetron (2?×?40 µg/kg d-1) with or without fosaprepitant (4 mg/kg; single dose, max. 1?×?150 mg/kg BW), and were analyzed in the control (CG; n?=?60) or fosaprepitant group (FG; n?=?60). The efficacy and safety of the two antiemetic prophylaxis regimens were analyzed and compared with respect to the acute (0-24 h) and the delayed (>?24-120 h) CINV phase and?>?120-240 h after MEC or HEC administration. RESULTS:During MEC, significantly more patients in the CG experienced vomiting during the first 0-24 h (58.6 vs. 25.0%; p?=?0.0156) and during?>?24-120 h (93.1% vs. 57.1%; p?=?0.0020), compared with the FG. Likewise, significantly more vomiting events (269 vs. 136; p??0.05). CONCLUSIONS:Antiemetic prophylaxis with fosaprepitant and granisetron was well tolerated, safe, and effective in pediatric patients undergoing alloHSCT. However, larger prospective trials are necessary to evaluate these findings.

SUBMITTER: Cabanillas Stanchi KM

PROVIDER: S-EPMC7085480 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Antiemetic prophylaxis with fosaprepitant and granisetron in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

Cabanillas Stanchi Karin Melanie KM Vek Julia J Schlegel Patrick P Rupprecht Joachim Vincent JV Flaadt Tim T Weber Simone S Michaelis Sebastian S Lang Peter P Handgretinger Rupert R Döring Michaela M

Journal of cancer research and clinical oncology 20200213 4

<h4>Background</h4>Chemotherapy-induced nausea and vomiting (CINV) is a severe and distressing complication during allogeneic hematopoietic stem cell transplantation (alloHSCT). The antiemetic fosaprepitant has shown favorable results in pediatric and adult patients receiving chemotherapy. Data on fosaprepitant in children and adolescents undergoing alloHSCT are missing.<h4>Methods</h4>In this non-interventional observation study, 120 children and adolescents with a median age of 11.8 years unde ...[more]

PMID: 32056007

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Project description:Background High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available. Methods A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8–32 mg/24h) or granisetron (2 x 40 µg/kg?d?1) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0–24h, >24–120h, >120–240h). Results Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (p>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0–24h (64 vs 22 events; p<0.01), >24–120h (135 vs 78 events; p<0.0001), >120–240h (268 vs 105 events; p<0.0001), and the whole observation period 0–240h (467 vs 205 events; p<0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24–120h (100% vs 74.3%) but not the other analyzed time periods (p>0.05). Conclusion The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.

Project description:Pharmacogenomics can explain the inter-individual differences in response to drugs, including methotrexate (MTX) used for acute graft-versus-host disease (aGVHD) prophylaxis during hematopoietic stem cell transplantation (HSCT). In real-world practice, preplanned MTX dose is arbitrarily modified according to observed toxicity which can lead to unexpected and severe aGVHD development. We aimed to validate the influence of MTHFR C677T polymorphism on the outcomes of allogenic HSCT in a relatively under-represented homogenous Asian population. A total of 177 patients were divided into 677TT group versus 677C-carriers (677CT+677CC), and clinical outcomes along with baseline characteristics were analyzed and compared. Although there was a tendency towards increased peak liver function test results and accordingly greater delta values between the highest and the baseline in 677TT group, we found no associations between genotypes and hepatotoxicity. However, the incidence of acute liver GVHD (? grade 2) was significantly higher in the 677TT group than in the 677CC + 677CT group (P = 0.016). A total of 25 patients (14.1%) expired due to transplantation related mortality (TRM) during the first 180 days after HSCT. Patients carrying 677TT genotype were more likely to experience early TRM than 677C-carriers. The same pattern was observed in the cumulative TRM rate, and 677TT genotype patients were more prone to cumulative TRM (P = 0.010). This translated into shorter OS for patients with 677TT compared to 677C-carriers (P = 0.010). The 3-year survival after HSCT was 29.9% for 677TT cases and 47.1% for 677C-carriers. The multivariate analysis identified 677TT genotype (HR = 1.775. 95% CI 1.122-2.808, P = 0.014) and non-CR state (HR = 2.841. 95% CI 1.627-4.960, P<0.001) as predictors for survival. In conclusion, the MTHFR 677TT genotype appears to be associated with acute liver GVHD, and represent a risk factor for TRM and survival in patients undergoing HSCT with MTX as GVHD prophylaxis.

Project description:BackgroundBacteremia is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear whether changes in the intestinal microbiota during allo-HSCT contribute to the development of bacteremia. We examined the microbiota of patients undergoing allo-HSCT, and correlated microbial shifts with the risk of bacteremia.MethodsFecal specimens were collected longitudinally from 94 patients undergoing allo-HSCT, from before transplant until 35 days after transplant. The intestinal microbiota was characterized by 454 pyrosequencing of the V1-V3 region of bacterial 16S ribosomal RNA genes. Microbial diversity was estimated by grouping sequences into operational taxonomic units and calculating the Shannon diversity index. Phylogenetic classification was obtained using the Ribosomal Database Project classifier. Associations of the microbiota with clinical predictors and outcomes were evaluated.ResultsDuring allo-HSCT, patients developed reduced diversity, with marked shifts in bacterial populations inhabiting the gut. Intestinal domination, defined as occupation of at least 30% of the microbiota by a single predominating bacterial taxon, occurred frequently. Commonly encountered dominating organisms included Enterococcus, Streptococcus, and various Proteobacteria. Enterococcal domination was increased 3-fold by metronidazole administration, whereas domination by Proteobacteria was reduced 10-fold by fluoroquinolone administration. As a predictor of outcomes, enterococcal domination increased the risk of Vancomycin-resistant Enterococcus bacteremia 9-fold, and proteobacterial domination increased the risk of gram-negative rod bacteremia 5-fold.ConclusionsDuring allo-HSCT, the diversity and stability of the intestinal flora are disrupted, resulting in domination by bacteria associated with subsequent bacteremia. Assessment of fecal microbiota identifies patients at highest risk for bloodstream infection during allo-HCST.

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Antiemetic prophylaxis with fosaprepitant and granisetron in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

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Antiemetic prophylaxis with fosaprepitant and granisetron in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

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