L. Lee Dupuis

Meta-Analysis of Randomized Controlled Trials of Prophylactic Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor After Autologous and Allogeneic Stem Cell Transplantation

PURPOSE The primary objective of our meta-analysis was to determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) after hematopoietic autologous and allogeneic stem-cell transplantation (SCT) reduced documented infections. Our secondary objectives were to determine whether prophylactic CSFs affected other outcomes including parenteral antibiotic therapy duration, infection-related mortality, graft-versus-host disease (GVHD), or treatment-related mortality. METHODS We included studies if there was random assignment between CSFs and placebo/no therapy and CSFs were given after SCT and before recovery of neutrophils. From 3,778 reviewed study articles, 34 were included based on predefined inclusion criteria. All analyses were conducted using a random effects model. RESULTS CSFs reduced the risk of documented infections (relative risk [RR] 0.87; 95% CI, 0.76 to 1.00; P = .05) and duration of parenteral antibiotics (weighted mean difference, -1.39 days, 95% CI, -2.56 to -0.22; P = .02) but did not reduce infection-related mortality (RR, 0.76; 95% CI, 0.41 to 1.44; P = .4). CSFs did not increase grade 2 to 4 acute GVHD (RR, 1.03; 95% CI, 0.81 to 1.31; P = .8) or treatment-related mortality (RR, 1.00; 95% CI, 0.78 to 1.29; P = .98). CONCLUSION CSFs were associated with a small reduction in the risk of documented infections but did not affect infection or treatment-related mortality.

Guideline for the Prevention of Acute Nausea and Vomiting Due to Antineoplastic Medication in Pediatric Cancer Patients

This guideline provides an approach to the prevention of acute antineoplastic‐induced nausea and vomiting (AINV) in children. It was developed by an international, inter‐professional panel using AGREE and CAN‐IMPLEMENT methods. Evidence‐based interventions that provide optimal AINV control in children receiving antineoplastic agents of high, moderate, low, and minimal emetogenicity are recommended. Recommendations are also made regarding selection of antiemetic agents for children who are unable to receive corticosteroids for AINV control, the role of aprepitant and optimal doses of antiemetic agents. Gaps in the evidence used to support the recommendations were identified. The contribution of this guideline to AINV control in children requires prospective evaluation. Pediatr Blood Cancer 2013; 60: 1073–1082.

Predictors of Viridans Streptococcal Shock Syndrome in Bacteremic Children With Cancer and Stem-Cell Transplant Recipients

PURPOSE To describe episodes of viridans streptococcal bacteremia (VSB) in a cohort of children with cancer and stem-cell transplant (SCT) recipients and to determine predictors of viridans streptococcal shock syndrome (VSSS) in this group of children. PATIENTS AND METHODS For this retrospective review, we included episodes of VSB isolated between March 1997 and September 2002, in children (<or= 18 years) with a diagnosis of cancer or SCT patients. The primary outcome was VSSS, defined as hypotension requiring intravascular volume expansion or inotropic support and/or respiratory insufficiency necessitating assisted ventilation. RESULTS Eighty-eight episodes of VSB occurred in 79 children. The mean age of the children was 6.7 years (range, 0.6 to 18.0 years). The most common underlying diagnosis was acute myelogenous leukemia (AML) in 31 (35%) of 88 episodes, and 38 (43%) of 88 had undergone SCT. VSSS occurred in 16 (18%) of 88 episodes, and two children died from VSSS. Two variables were predictive of VSSS, namely peak temperature at presentation (odds ratio [OR], 6.3; 95% CI, 2.1 to 19.0; P =.001) and inpatient status (OR, 5.9; 95% CI, 1.3 to 28.0; P =.02). Diagnosis of AML (OR, 1.1; 95% CI, 0.4 to 3.5; P =.8), receipt of SCT (OR, 1.9; 95% CI, 0.6 to 5.7; P =.2), high-dose cytarabine (OR, 0.6; 95% CI, 0.1 to 3.2; P =.6), and mucositis (OR, 0.8; 95% CI, 0.3 to 2.6; P =.7) were not predictive of VSSS. CONCLUSION VSSS occurred in 18% of episodes of VSB in children with cancer or SCT recipients. Peak temperature before antibiotic therapy and inpatient status were predictive of VSSS.

Guideline for the classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients.

This guideline provides clinicians caring for children with an approach to assessing the acute emetogenic potential of antineoplastic therapies. It was developed by an international, inter‐professional panel of clinicians and researchers using AGREE and CAN‐ADAPTE methods. The emetogenicity of antineoplastic agents was evaluated and ranked as high, moderate, low, or minimal. The emetogenicity of multiple‐agent and multiple‐day antineoplastic therapy was also classified. Gaps in the evidence used to underpin the guideline recommendations were identified. The contribution of this guideline to the prevention of antineoplastic‐induced nausea and vomiting in individual children about to receive antineoplastic therapy requires prospective evaluation. Pediatr Blood Cancer 2011; 57: 191–198.

Defibrotide for the treatment of hepatic veno-occlusive disease in children.

This retrospective report describes experience with defibrotide in children with hepatic veno‐occlusive disease (HVOD) following hematopoietic progenitor cell transplant (HPCT) in a single institution.

Development and Validation of the Pediatric Nausea Assessment Tool for Use in Children Receiving Antineoplastic Agents

Study Objective. To develop and validate an instrument to assess nausea intensity in children aged 4–18 years.

Options for the Prevention and Management of Acute Chemotherapy-Induced Nausea and Vomiting in Children

The current standard of care with respect to preventing acute chemotherapy-induced nausea and vomiting (CINV) in children includes the administration of a 5-HT3 antagonist with or without a corticosteroid, depending on the emetogenicity of the chemotherapy to be given. Problems in assessing the emetogenicity of chemotherapy regimens and nausea severity in children may influence the degree of success of CINV prophylaxis. Nevertheless, the majority of children who receive chemotherapy today experience moderate to complete control of acute CINV when given appropriate antiemetic prophylaxis. If children vomit or experience nausea despite appropriate prophylaxis, then measures must be taken to treat these symptoms since these children are likely to go on to experience delayed or anticipatory CINV. However, appropriate selection of interventions to treat acute CINV in children is limited by the lack of rigorous evidence to support one approach over another. Lorazepam is suggested as an immediate agent for the treatment of acute CINV. Doses and frequencies of the 5-HT3 antagonist and corticosteroid administered for initial prophylaxis should also be maximized. Further treatment must be tailored to the circumstances and preferences of each child and family. Options include crossover to another 5-HT3 antagonist, or administration of an adjunctive antiemetic such as metopimazine, low dose metoclopramide, domperidone, alizapride, nabilone, scopolamine, prochlorperazine, or chlorpromazine. Complementary interventions such as acupuncture, hypnosis, counseling, or ginger may also be of benefit. Further study is required to establish optimal antiemetic strategies in children.

Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children--a systematic review of prospective trials.

BackgroundThere is no consensus on whether therapeutic intensity can be reduced safely in children with low-risk febrile neutropenia (FN). Our primary objective was to determine whether there is a difference in efficacy between outpatient and inpatient management of children with low-risk FN. Our secondary objective was to compare oral and parenteral antibiotic therapy in this population.MethodsWe performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in low-risk FN. Percentages were used as the effect measure.ResultsFrom 7,281 reviewed articles, 16 were included in the meta-analysis. Treatment failure, including antibiotic modification, was less likely to occur in the outpatient setting compared with the inpatient setting (15 % versus 28 %, P = 0.04) but was not significantly different between oral and parenteral antibiotic regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the outpatient setting and 676 episodes treated with oral antibiotics, none were associated with infection-related mortality.ConclusionBased on the combination of results from all prospective studies to date, outpatient and oral antibiotic management of low-risk FN are effective in children and should be incorporated into clinical care where feasible.

Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children with down syndrome

Acute lymphoblastic leukemia (ALL) in children with Down syndrome (DS) presents with an increased incidence, higher frequency of adverse effects and inferior probability of survival. Attempts at improving outcomes face the dilemma posed by the need to avoid excessive toxicity while maintaining the efficacy of treatment. Dose reductions and avoidance of infusions of intermediate and high‐dose methotrexate are common in this group.

Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update

Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.