This update of the 2013 clinical practice guideline provides clinicians with guidance regarding the use of aprepitant and palonosetron for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) in children. The recommendations were based on three systematic reviews. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5-HT antagonists recommended for children receiving highly emetogenic chemotherapy (HEC) and the recommendation of aprepitant for children 6 months of age or older receiving HEC. To optimize CINV control in children, future work must focus on closing critical research gaps.

BACKGROUND AND OBJECTIVES: Hospitalized infants, children, and adolescents are typically exposed to numerous distinct medications during inpatient admissions, increasing their risk of potential drug2drug interactions (PDDIs). We assessed the prevalence and characteristics of PDDI exposure of pediatric patients treated in children's hospitals.

BACKGROUND: Pediatric patients with cancer face more severe complications of influenza than healthy children. Although Centers for Disease Control and Prevention guidelines recommend yearly vaccination in these patients, in our large academic center, ,60% of oncology patients receiving chemotherapy were immunized at baseline. Our objective was to increase this rate through a multifaceted quality improvement initiative.METHODS: Eligible patients were .6 months old, within 1 year of receiving chemotherapy, .100 days from stem cell transplant, and had $1 outpatient oncology visit between September 1, 2012, and March 31, 2013. Five interventions were instituted concomitantly: (1) family education: influenza/ vaccine handouts were provided to families in clinic waiting rooms; (2) health informatics: daily lists of outpatients due for immunization were generated from the electronic medical record and sent automatically to triage staff and nurses; (3) outpatient clinic: patients due for vaccination were given colored wristbands during triage to alert providers; (4) inpatient: vaccine order was built into admission order set; and (5) provider education: staff education was provided at conferences on screening of patients, vaccine ordering, and documentation of refusals/contraindications. RESULTS:The complete influenza immunization rate increased by 20.1% to 64.5%, and the proportion of patients receiving $1 dose of vaccination increased by 22.9% to 77.7%. Similar changes were noted across all cancer types, with highest rates of immunization in leukemia/lymphoma patients (86.8%) and lowest in patients after stem cell transplant (66.7%).CONCLUSIONS: Technology, education, and multidisciplinary clinical process changes increased influenza vaccination rates. Ongoing efforts are targeting subgroups with lowest rates of immunization.

This clinical practice guideline (CPG) provides clinicians with recommendations regarding chemotherapy emetogenicity classification in pediatric oncology patients. This information is critically important for the appropriate selection of antiemetic prophylaxis. Recommendations are based on a systematic review limited to pediatric patients and a framework for classification when antiemetic prophylaxis is provided. Findings of 87 publications informed the emetogenicity classification of 49 single‐agent and 13 combination‐agent regimens. Information required for the classification of many chemotherapies commonly administered to pediatric patients is lacking. In the absence of pediatric data, consultation of methodologically sound CPGs aimed at adult oncology patients may be appropriate.

PURPOSE To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600). CONCLUSION Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.

Atypical chronic myeloid leukemia, BCR-ABL1-negative, (aCML) is a rare myeloid neoplasm. Recent adult data suggest the leukemic cells in a subset of patients are dependent on JAK/STAT signaling and harbor CSF3R-activating mutations. We hypothesized that, similar to adult patients, the presence of CSF3R-activating mutations would be clinically relevant in pediatric myeloid neoplasms as patients would be sensitive to the JAK inhibitor, ruxolitinib. We report two cases of morphologically similar pediatric aCML, BCR-ABL1-negative based on WHO 2008 criteria. One patient had CSF3R-activating mutation (T618I) and demonstrated a robust response to ruxolitinib, which was used to bridge to a successful stem cell transplant. The other patient did not have a CSF3R-activating mutation and succumbed to refractory disease <6 months from diagnosis. This report documents CSF3R-T618I in pediatric aCML and demonstrates the efficacy of ruxolitinib in a pediatric malignancy. As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms.

Background The Children’s Oncology Group (COG) has endorsed a clinical practice guideline (CPG) for acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis in children with cancer. This project aims to describe current acute CINV prophylaxis practice at COG sites and the gap between this practice and CPG recommendations. Procedure Two surveys were developed. The first survey, sent to 94 Cancer Control and Supportive Care Responsible Individuals (CCL RIs) at 94 COG institutions, asked if the institution had a standardized approach to practice and focused on antiemetic agent choice. The second survey, sent to 54 pharmacists at COG sites where the CCL RI indicated there was a standardized approach to CINV prophylaxis practice, focused on antiemetic dosing. Survey results were described and analyzed for consistency with the CPG recommendations. Results Among the 69 respondents to the first survey, 54 (78%) stated that their institutions have a standardized approach to CINV prophylaxis practice. However, antiemetic choice practices varied widely among respondents. Results from the 36 respondents to the second survey also demonstrated significant antiemetic dosing practice variability. Frequent sources of deviation from CPG recommendations were: antiemetic choice when corticosteroids are contraindicated, dexamethasone dosing, aprepitant use in children less than 12 years and aprepitant use in the presence of a known or suspected drug interaction. Conclusions There is great diversity in the CINV prophylaxis provided to children with cancer at COG sites. Concerted strategies are required to improve awareness of the current CINV prophylaxis CPG and to facilitate CPG-consistent CINV prophylaxis.