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A 2.5-year-old boy presented to his pediatrician with progressive pallor, asthenia, fever, splenomegaly, and hematomas. Leukemia was suspected, and a bone marrow aspirate confirmed acute lymphoblastic leukemia. Before chemotherapy induction, the child developed a vesicular rash and was diagnosed clinically with chickenpox. Acyclovir treatment was initiated immediately, whereas induction chemotherapy was postponed by 10 days. At the time of chickenpox resolution, a spontaneous partial recovery of his blood counts and a 50% decrease of blastic bone marrow infiltration were noted. After a brief nonsystematic review, we discuss the potential beneficial effect of acyclovir and chickenpox infection in children with leukemia.

(1) Background: Superior cerebellar peduncle (SCP) lesions are sparsely reported in the literature. The surgical approaches to the cerebello-mesencephalic region remain challenging. In this article, we present the extreme lateral supracerebellar infratentorial (ELSI) approach to treat a large hemorrhagic pilocytic astrocytoma of the SCP. (2) Methods: An 11-year-old boy, known for neurofibromatosis Type I, presented to the emergency department of our institution with symptoms and signs of intracranial hypertension. The cerebral magnetic resonance imaging (MRI) revealed a large hemorrhagic lesion centered on the SCP provoking obstructive hydrocephalus. Following an emergency endoscopic third ventriculocisternostomy (ETV), he underwent a tumor resection via an endoscope-assisted ELSI approach. (3) Results: ELSI approach allows for a wide exposure with direct access to lesions of the SCP. The post-operative course was uneventful, and the patient was discharged home on post-operative day 5. Post-operative MRI revealed a near total resection with a small residual tumor within the mesencephalon. (4) Conclusion: ELSI approach offers an excellent exposure with the surgical angles necessary for median and paramedian lesions. The park-bench position with appropriate head flexion and rotation offers a gravity-assisted relaxation of the tentorial and petrosal cerebellar surfaces. The endoscope can be an adjunct to illuminate the blind areas of the surgical corridor for an improved tumor resection without significant cerebellar retraction.

Despite recent improvements in survival rates in children with cancer, long-term toxicities remain a major concern. Physical activity could reduce the impact of long-term sequelae, notably in neuropsychological and physical areas. We report of a randomized trial of pure physical versus physical/attentional training in pediatric oncology patients. Twenty-two patients aged 6-18 y.o. were included, irrespective of their clinical diagnosis or treatment status, stratified by age and randomized 1:1 into pure physical vs. physical/attentional activity arms, with a cross-over at study midpoint. Neurological, motor and neuropsychological assessments were performed at inclusion, start, crossover and end of the program. Feasibility, defined as > 80% patients attending > 80% of sessions, was the primary endpoint. Secondary outcomes were improvements in neuropsychological and motor performance tests. While 68% of patients attended more than 80% of sessions during the pre-crossover phase of the study, this dropped to 36% post-crossover. Our study therefore failed to meet our primary endpoint. Nonetheless, significant improvements in anxiety (p

Purpose Benzene is a known carcinogen for adult leukemia. Exposure to benzene through parental occupation and the use of household products has been associated with childhood leukemia (CL). Ambient benzene has also been associated with CL and central nervous system (CNS) tumors. We aimed to investigate whether the higher ambient levels of benzene in proximity of petrol stations are associated with a greater risk of childhood cancers, leukemia, and CNS tumors. Methods We identified children diagnosed with cancer at age 0–15 years during 1985–2015 from the Swiss Childhood Cancer Registry and selected 10 age and sex-matched controls per case from national censuses. We calculated the distance from children’s home to the nearest petrol station using precise geocodes. We estimated odds ratios using conditional logistic regression adjusting for ambient levels of NO2, distance to highways, level of urbanization, and presence of a cantonal cancer registry. In addition, we ran a meta-analysis pooling current results for CL with those of previous studies. Results We identified 6129 cases, of which 1880 were leukemias and 1290 CNS tumors. 24 cases lived within 50 m from a petrol station. The adjusted odds ratio of a cancer diagnosis for children thus exposed compared to unexposed children (> 500 m) was 1.29 (0.84–1.98) for all cancers combined, 1.08 (0.46–2.51) for leukemia, and 1.30 (0.51–3.35) for CNS tumors. During 2000–2015, when exposure assessment was more precise, the adjusted odds ratio for any cancer diagnosis was 1.77 (1.05–2.98). The summary relative risk estimate for CL in the meta-analysis including four studies was 2.01 (1.25–3.22). Conclusions Our study provides weak support for an increased risk of childhood cancers among children living close to petrol stations. A meta-analysis including our study suggests an increased risk for CL.

BackgroundImprovement of paediatric healthcare is hampered by inefficient processes of generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardized between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality.AimsSwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based common data model (CDM) that covers all processes of routine paediatric care in hospitals.MethodsA taskforce of paediatricians from large Swiss children’s hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalization. We then used a modified Delphi method to reach a broad consensus on a national EHR-based CDM.ResultsAll Swiss children’s hospitals use EHR to document some or all aspects of care. 119 paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national CDM that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 common data elements (CDEs): 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional.ConclusionSwissPedData is a CDM for information to be collected in EHR of Swiss children’s hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

Background The prevalence of complementary and alternative medicine (CAM) use and the modalities used by pediatric oncology patients vary widely across studies. In addition, the changes in the use of CAM over the course of treatment are understudied. Thus, this study aimed to explore (1) CAM use by pediatric oncology patients in relation to specific time intervals and (2) communication about CAM use between parents and oncologists. Methods This retrospective cross-sectional study was conducted among parents of children diagnosed with cancer at a Swiss pediatric hematology-oncology center by means of an online questionnaire. Questions were related to their child’s CAM use over different time intervals, sources of information about CAM use, and communication with the oncologists. Results Among 140 respondents, CAM was used by 54.3% of patients before diagnosis and 69.3% of patients after diagnosis. During each defined time interval, between 50 and 58.8% of the patients used at least one CAM. Homeopathy was the most popular CAM modality used during oncology treatment, during the first year after treatment, and between 1 and 5 years after the end of treatment. Osteopathy was the most popular CAM ≥5 years after the end of oncology treatment. Forty percent of respondents did not discuss CAM with their oncologist. Conclusions The high prevalence of CAM use and the different trends of use during the oncology care pathway and afterward underline the need to increase communication about CAM in the pediatric oncology setting, notably regarding benefits and risks of interaction with oncology treatment.

Background: Neonicotinoids (NN) are selectively neurotoxic pesticides that bind to insect but also mammals nicotinic acetycholine receptors (nAChRs). As the most widely used class of insecticides worldwide, they are ubiquitously found in the environment, wildlife, and foods and thus of special concern for their impacts on the environment and human health. nAChRs are vital to proper brain organization during the prenatal period and play important roles in various motor, emotional, and cognitive functions. Little is known on children’s contamination by NN. In a pilot study we tested the hypothesis that children's cerebro-spinal fluid (CSF) can be contaminated by NN. Methods: NN were analysed in leftover CSF, blood, and urine samples from children treated for leukaemias and lymphomas and undergoing therapeutic lumbar punctions. We monitored all neonicotinoids approved on the global market and some of their most common metabolites by ultra-high performance liquid chromatography-tandem mass spectrometry. Findings: From August to December 2020, 14 children were consecutively included. Median age was 8 years (range 3-18). All CSF and plasma samples were positive for at least one NN. Nine (64%) CSF samples and 13 (93%) plasma samples contained more than one NN. Thirteen (93%) CSF samples had desmethyl-acetamiprid (median 0·0123, range 0·0024-0·1068 ng/mL). All but one urine samples were positive for ≥ one NN. Interpretation: Multiple NN and/or their metabolites are present in children's CSF, plasma, and urine. Our data suggest that contamination by multiple NN is not only an environmental hazard for non-target insects such as bees but also potentially for children. Funding: Lausanne University Hospital, University of Neuchâtel, Stichting Triodos Foundation (The Netherlands), for the Institutional Review Board fees, NN analysis costs, and Open Source publication fees if relevant. Declaration of Interest: AA and EM are members of the IUCN Task Force on Systemic Pesticides. MISSING OTHER AUTHORS ON DOI Ethical Approval: The study was approved by our local Institutional Review Board (Commission cantonale d'ethique de la recherche sur l'etre humain, CER-VD).

Targeting of the most aggressive tumor cell subpopulations is key for effective management of most solid malignancies. However, the metastable nature of tumor heterogeneity, which allows cells to transition between strong and weak tumorigenic phenotypes, and the lack of reliable markers of tumor-promoting properties hamper identification of the most relevant cells. To overcome these obstacles, we designed a functional microRNA (miR)-based live-cell reporter assay to identify highly tumorigenic cells in xenotransplants of primary Ewing sarcoma (EwS) 3D cultures. Leveraging the inverse relationship between cell pluripotency and miR-145 expression, we successfully separated highly tumorigenic, metastasis-prone (miR-145 low ) cells from poorly tumorigenic, nonmetastatic (miR-145 high ) counterparts. Gene expression and functional studies of the two cell populations identified the EPHB2 receptor as a prognostic biomarker in patients with EwS and a major promoter of metastasis. Our study provides a simple and powerful means to identify and isolate tumor cells that display aggressive behavior.

Introduction Pediatric neuroendocrine tumors (NETs) of the appendix are mostly detected incidentally after appendectomy for acute appendicitis. NET management is a matter of controversy. In this national, multicenter study, we aimed to establish guidelines based on our results and the literature. Materials and Methods Medical records of children (0–16 years) with NET of the appendix, treated in Switzerland (1991–2012), were reviewed. Results Forty cases (28 girls) were analyzed. Median age at diagnosis was 12.7 years (interquartile range [IQR]: 4.0). Tumor size was 0.1–24 mm (median: 0.6, IQR: 0.6). Four patients (10%) underwent additional surgery because of either tumor size > 15 mm (1/4), extension to the mesoappendix (1/4), or incomplete resection (2/4). Three patients with a tumor of ≥ 20 mm had no additional surgery. No patient had lymph node metastases. All patients were in complete remission at the last follow-up (median: 3.0 years, IQR: 10.9). Conclusion We conclude from this study and from an extensive review of the literature that two criteria may point to the need for additional surgery, i.e., the possibility of regional lymph node involvement: tumor size > 20 mm and incomplete surgical resection margins. Childhood NET of the appendix has an excellent prognosis.

Contains fulltext : 242783.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To capture the early effects of the coronavirus disease 2019 (COVID-19) pandemic on pediatric clinical research. STUDY DESIGN: Pediatric clinical research networks from 20 countries and 50 of their affiliated research sites completed two surveys over one month from early May to early June 2020. Networks liaised with their affiliated sites and contributed to the interpretation of results through pan-European group discussions. Based on first detection dates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), countries formed 1 early detecting and 1 late detecting cluster. We tested the hypothesis that this clustering influenced clinical research. RESULTS: Research sites were first impacted by the pandemic in mid-March 2020 (March 16 ± 10 days, the same date as lockdown initiation; P = .99). From first impact up until early June, site initiation and feasibility analysis processes were affected for >50% of the sites. Staff were redirected to COVID-19 research for 44% of the sites, and 75.5% of sites were involved in pediatric COVID-19 research (only 6.3% reported COVID-19 cases in their other pediatric trials). Mitigation strategies were used differently between the early and late detecting country clusters and between countries with and without a pediatric COVID-19 research taskforce. Positive effects include the development of teleworking capacities. CONCLUSIONS: Through this collaborative effort from pediatric research networks, we found that pediatric trials were affected and conducted with a range of unequally applied mitigations across countries during the pandemic. The global impact might be greater than captured. In a context where clinical research is increasingly multinational, this report reveals the importance of collaboration between national networks.

Introduction Data regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I-II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC). Methods A survey was sent to all ITCC-accredited Early-Phase Clinical Trial Hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1/March and 30/April/2020. Results Thirty-one out of 53 hospitals from 12 countries participated. Challenges reported included staff constraints (30% drop), reduction in planned monitoring activity (67% drop of site initiation visits and 64% of monitoring visits) and patient recruitment (61% drop compared to 2019). The percentage of phase I, phase II trials and molecular platforms closing to recruitment in at least one site was 48.5%, 61.3% and 64.3%, respectively. Additionally, 26% of sites had restrictions on performing trial assessments due to local contingency plans. Almost half of the units suffered impact upon pending contracts. Most hospitals (65%) are planning on improving organizational and structural changes. Conclusion The study reveals a profound disruption of paediatric cancer early phase clinical research due to the COVID-19 pandemic across Europe. Reported difficulties affected both patient care and monitoring activity. Efforts should be made to reallocate resources to avoid lost opportunities for patients and to allow the continued advancement of oncology research. Identified adaptations to clinical trial procedures may be integrated to increase preparedness of clinical research to futures crises., Highlights • The COVID-19 pandemic has profoundly disrupted paediatric cancer clinical research. • A drastic drop in recruitment in phase I/II trials compared to 2019 was observed. • Current research needs reorganization to avoid loss of opportunities for children.

Midazolam is commonly used to treat refractory seizures in newborns and as a first-line anti-epileptic drug in children. Its use as first-line treatment of neonatal seizures has not been investigated so far. We retrospectively studied the tolerability of midazolam in 72 newborn infants who received i.v. or i.n. midazolam as first-line treatment for seizures. No major side-effect exclusively due to midazolam was reported. The i.n. route was used for 20 patients (27.8%). Effectiveness could not be formally evaluated due to the absence of systematic electroencephalogram recording while midazolam was administered. In conclusion, midazolam was well-tolerated as a first-line abortive emergency treatment of neonatal seizure. The i.n. route offers a useful alternative to i.v. phenobarbital or phenytoin in emergency settings.

Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic, PRISMA-based review of the literature, available clinical guidelines and practice recommendations. We also aimed to extract any valuable information for the "best of available-evidence"-based prevention of perioperative adverse events in children with SCD, and highlight the most urgent priorities in clinical research. As data sources, US National Library of Medicine, Medline, National Guideline Clearinghouse, International Guideline Network, TRIP databases were searched for any content until January 2019. We also included institutional, consortia and expert group guidelines. Included were reports/guidelines in English, French, German, and Italian. Excluded were reports on obstetrical and fetal management. We identified 202 reports/guidelines fulfilling the criteria outlined above. A majority focused on visceral, cardiovascular and orthopedic surgery procedures, and only five were multicenter randomized controlled trials and two prospective randomized studies. After grading of the quality of the evidence, the extracted data was summarized into clinical recommendations for daily practice. Additionally, we designed a risk-grading algorithm to identify contexts likely to be associated with adverse outcomes. In conclusion, we provide a systematic PRISMA-based review of the existing literature and ancillary practice and delineate a set of clinical recommendations and priorities for research.

Non anemic iron deficiency (NAID) is the most common nutritional deficiency. Symptoms more frequently observed in children and adolescents include fatigue, delayed psychomotor development as well as decreased school and athletic performances. Iron treatment is effective in improving symptoms in older children and adolescents. In children under 2 years of age, there is currently no evidence of the efficacy of substitution therapy on development. Preemptive treatment is not justified considering the available evidence beyond premature or small newborns for gestational age and should only be initiated if a diagnosis of iron deficiency is confirmed. Oral iron supplementation is the first-line treatment of NAID.La carence en fer sans anémie (CF-sA) est le déficit nutritionnel le plus répandu. Les symptômes plus fréquemment observés chez l’enfant et l’adolescent sont une fatigue, un retard de développement psychomoteur et une diminution des performances scolaires et sportives. Une substitution martiale s’avère efficace dans l’amélioration de ces symptômes chez le grand enfant et l’adolescent. Chez l’enfant d’âge inférieur à deux ans, il n’existe actuellement pas d’évidence de l’efficacité d’un traitement substitutif sur le plan du développement. Un traitement préemptif, en dehors de la prématurité ou d’un retard de croissance intra-utérin, n’est à l’heure actuelle pas justifié en considérant l’évidence disponible, et devrait être débuté uniquement suite à un diagnostic formel de carence martiale. Le traitement de première intention de la CF-sA, en l’absence de contre-indications, est le traitement oral.

Fighting leukemia using the immune system (antibodies, lymphocytes) is an old idea, which has already been fulfilled in allogeneic bone marrow transplantation. Indeed, the effectiveness of the transplant depends on the action of the donor lymphocytes. To limit the adverse effects on bystander organs (graft-versus-host disease), autologous T cells can be engineered to express synthetic chimeric antigen receptors (CARs) with artificially redirected antigen specificity. Autologous T cells engineered to express a CAR targeting CD19 have shown unprecedented efficacy in clinical trials for relapsed/refractory B-cell leukemias and lymphomas. In this review article, we describe the therapeutic strategies, clinical trial results, side effects and future direction of CAR T cell therapy in B cell acute lymphoblastic leukemia and other pediatric cancers and its future role in the Swiss setting.Combattre la leucémie en utilisant les armes immunologiques, via les anticorps et les lymphocytes, est une idée ancienne, qui a déjà connu un accomplissement dans la greffe de moelle osseuse. Pour limiter les effets néfastes sur d’autres organes (maladie du greffon contre l’hôte), des cellules T autologues peuvent être modifiées pour exprimer des récepteurs d’antigènes chimères synthétiques (CAR) avec spécificité antigénique. Dans le cadre d’essais cliniques, les cellules CAR-T anti-CD19 ont montré une efficacité importante dans les leucémies et les lymphomes B en rechute ou réfractaires. Dans cet article, nous décrivons les approches proposées, les résultats des essais cliniques, les effets secondaires et l’orientation future de ces thérapies dans les leucémies et d’autres cancers pédiatriques ainsi que leurs perspectives dans le contexte suisse.

PURPOSE Hearing loss, a complication of cancer treatment, may reduce health-related quality of life (HRQoL), especially in childhood cancer survivors of central nervous system (CNS) tumours who often have multiple late effects. We examined the effect of hearing loss on HRQoL in young survivors of CNS and other childhood cancers. METHODS Within the Swiss Childhood Cancer Survivor Study, we sent questionnaires about hearing loss and HRQoL (KIDSCREEN-27) to parents of survivors aged 8-15 years. We stratified the effect of hearing loss on HRQoL by cancer diagnosis, using multivariable logistic regression and adjusting for sociodemographic and clinical factors. RESULTS Hearing loss was associated with impaired physical well-being [unadjusted estimated differences - 4.6 (CI - 9.2, - 0.1); adjusted - 4.0 (CI - 7.6, - 0.3)] and peers and social support [unadjusted - 6.7 (CI - 13.0, - 0.3); adjusted - 5.0 (CI - 10.5, 0.9)] scores in survivors of CNS tumours (n = 123), but not in children diagnosed with other cancers (all p-values > 0.20, n = 577). CONCLUSION Clinicians should be alert to signs of reduced physical well-being and impaired relationships with peers. Especially survivors of CNS tumours may benefit most from strict audiological monitoring and timely intervention to mitigate secondary consequences of hearing loss on HRQoL.

A sensitive and selective method of high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active metabolites (regorafenib-M2 and regorafenib-M5) in human plasma. Plasma protein precipitation with methanol enables the sample extraction of 100 μL aliquot of plasma. Analytes are detected by electrospray triple-stage quadrupole mass spectrometry and quantified using the calibration curves with stable isotope-labeled internal standards. The method was validated based on FDA recommendations, including assessment of extraction yield (74-104%), matrix effects, analytical recovery (94-104%) with low variability (

BackgroundBroad-spectrum beta-lactams such as meropenem (MER) and piperacillin-tazobactam (PIP) are commonly prescribed in children with cancer having febrile neutropenia. They are introduced at intensive dosage, unless decreased renal function calls for dose reduction. Recently, glomerular hyperfiltration (HF) was recognized to be frequent among children with cancer during initial cycles of chemotherapy.1 We evaluated the impact of HF on therapeutic exposure to MER and PIP.MethodsWe retrieved retrospectively all MER and PIP plasma levels measured in children with cancer in our hospital between 2012 and 2018. We compared trough levels with usual therapeutic ranges (derived from reference values of minimum inhibitory concentrations). We classified the children according to plasma creatinine and estimated glomerular filtration rate (Schwartz formula) as either altered-normal (< 160 mL/min/1.73 m2) or increased (i.e. HF, ≥160). Neutropenia was defined as absolute neutrophil count < 500 cells/µL.ResultsWe collected 120 concentration values (53 MER, 67 PIP) measured in 50 children with cancer. Among them, 74 (62%) had concomitant creatinine values suggestive of HF, and 80 (67%) were neutropenic. Overall, 67% of trough levels were below usual therapeutic ranges (MER: 2–8 mg/L, PIP 8–30 mg/L). This was more often the case in presence of concomitant HF (MER: 92%, PIP: 83%), often associated with neutropenia. Low exposure was observed not only at initial intensive dosage (MER: 120 mg/kg/day, PIP: 400 mg/kg/day)2 but tended to persist despite dosage readjustment based on concentration monitoring. Moreover, bacteremia was diagnosed in 38 cases.ConclusionCurrent recommended doses of MER and PIP do not provide optimal concentration coverage throughout the dosing interval in a large fraction of children with cancer and febrile neutropenia as a result of HF. Monitoring of beta-lactams should be offered to all children with cancer to ensure best therapeutic success and avoid the development of resistance.ReferencesKwatra NS, Meany HJ, Ghelani SJ, Zahavi D, Pandya N, Majd M. Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis. Pediatr Radiol 2017;47(2):221–226.The Lexicomp Pediatric & Neonatal Dosage Handbook, 21st edition, Lexicomp, USA.Disclosure(s)Nothing to disclose

Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha.Methods: European Societe Internationale d'Oncologie Pediatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth).Results: Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years.Conclusions: Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.

This study evaluates our institution's target trough cyclosporine (CSA) concentrations as predictors of severe acute graft versus host disease (aGvHD) in children receiving either matched related or unrelated hematopoietic stem cell transplantation (HSCT). The outcomes of 87 consecutive children who underwent allogeneic HSCT and received CSA and methotrexate as prophylaxis against aGvHD between October 1, 1999 and September 30, 2002 were retrospectively evaluated. The proportion of time that each patient maintained a whole blood CSA concentration within or above the initial target range (105-155 ng/mL or 155-210 ng/mL) was calculated for each of the following time periods: in each week after HSCT from day 0 to +28; in the week preceding engraftment; and in the week preceding the onset of aGvHD. Patients were prospectively evaluated twice weekly for the presence and severity of aGvHD by senior attending physicians. The relationship between potential predictors and the development of severe aGvHD was examined using univariate logistic regression. The main variables of interest were the proportion of time that therapeutic or supratherapeutic CSA concentrations were maintained; median CSA concentrations; the number of methotrexate doses received; and the use of folinic acid rescue. Mean follow-up time was 3.0+/-1.9 years among children who survived beyond day +100. Three variables were significantly associated with the development of severe aGvHD on univariate analysis: initial CSA target concentration [odds ratio (OR), 0.24; P=0.03], proportion of time the target CSA concentration was achieved during the second week after transplant (OR, 0.16; P=0.02), and proportion of time the target CSA concentration was achieved during the week before engraftment (OR, 0.22; P=0.0489). Multivariable analysis demonstrated an inverse relationship between the median CSA concentration during the week before engraftment and the development of severe aGvHD (OR, 0.99; P=0.045). These results suggest that achievement of our CSA target concentrations is important to aGvHD outcomes.

Trilateral retinoblastoma (TRb) is a well-known syndrome associating hereditary retinoblastoma (Rb) with an intracranial neuroblastic tumor arising usually in the pineal region, rarely at the suprasellar or parasellar site. It develops in most cases after diagnosis of Rb. The outcome is usually fatal because of secondary spinal dissemination. Pineal cysts have recently been reported as a benign variant of TRb. We report the unusual presentation of a TRb in a 12-month-old boy with extensive bilateral Rb, a voluminous suprasellar tumor, pineal cyst, and leptomeningeal disease. The special features of this "quadrilateral" Rb are discussed.

We report the case of a drug interaction between methotrexate (MTX) and chloral hydrate (CH) observed in a child treated for acute leukemia. Significantly slower MTX clearance and increased MTX exposure occurred on the first three courses of a high-dose chemotherapy when co-administered with CH despite normal renal function, adequate hydration, and alkalinization. Mean MTX area under the curve associated with CH administration was 1,134 µmol hours/L, compared to 608 µmol hours/L after discontinuation of CH. This interaction possibly resulted from a competition between anionic CH metabolites and MTX for renal tubular excretion. Pediatr Blood Cancer 2013; 60: 518–520. © 2012 Wiley Periodicals, Inc.

Drug-induced peripheral neuropathies are common, secondary to multiple drug classes, in particular chemotherapeutic agents. They have an important impact on patients' quality of life. In recent years, significant progress has been made in the understanding of some pathophysiological mechanisms. The use of more objective assessment tools should allow the development of individualized and more effective therapeutic strategies.

PURPOSE OF REVIEW This review discusses publications highlighting current research on toxic, chemotherapy-induced peripheral neuropathies (CIPNs), and drug-induced peripheral neuropathies (DIPNs). RECENT FINDINGS The emphasis in clinical studies is on the early detection and grading of peripheral neuropathies, whereas recent studies in animal models have given insights into molecular mechanisms, with the discovery of novel neuronal, axonal, and Schwann cell targets. Some substances trigger inflammatory changes in the peripheral nerves. Pharmacogenetic techniques are underway to identify genes that may help to predict individuals at higher risk of developing DIPNs. Several papers have been published on chemoprotectants; however, to date, this approach has not been shown effective in clinical trials. SUMMARY Both length and nonlength-dependent neuropathies are encountered, including small-fiber involvement. The introduction of new diagnostic techniques, such as excitability studies, skin laser Doppler flowmetry, and pharmacogenetics, holds promise for early detection and to elucidate underlying mechanisms. New approaches to improve functions and quality of life in CIPN patients are discussed. Apart from developing less neurotoxic anticancer therapies, there is still hope to identify chemoprotective agents (erythropoietin and substances involved in the endocannabinoid system are promising) able to prevent or correct painful CIPNs.

We report the case of a drug interaction between methotrexate (MTX) and chloral hydrate (CH) observed in a child treated for acute leukemia. Significantly slower MTX clearance and increased MTX exposure occurred on the first three courses of a high-dose chemotherapy when co-administered with CH despite normal renal function, adequate hydration, and alkalinization. Mean MTX area under the curve associated with CH administration was 1,134 µmol hours/L, compared to 608 µmol hours/L after discontinuation of CH. This interaction possibly resulted from a competition between anionic CH metabolites and MTX for renal tubular excretion.

Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI (n = 7) were significantly smaller (P = 0.02), and mainly asymptomatic than TRb detected later on (n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29–100 %) compared to 11 % (95 % CI 0–32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage.

Purpose Totally implanted vascular (TIVA) ports are used in children for repeated blood samples or intravenous treatments. We have recently published a prospective evaluation of surgical incidents and early complications associated with these devices. This work is the final part of the same study, assessing late complications over a follow-up of 2 yrs. Methods From January 2006 to January 2008, children older than 1 yr of age with a diagnosis of solid or blood cell malignancy were included. Insertion technique and care of the device were standardized. Every manipulation was prospectively recorded by specialized nurses. Obstruction was documented clinically. When bacteremia was suspected, routine central and peripheral blood cultures were drawn. Results Forty-five consecutive patients were enrolled in the study. Mean age at the time of the procedure was 8.5 yrs. There was no catheter-related infection within the first 4 weeks post-surgery. No device had to be removed because of infection or obstruction during follow-up. Frequent accesses to the port (≥3 per day over a 10–day period) were associated with an 8–fold risk of infection. Conclusion Insertion and use of TIVA devices were frequently associated with complications. No device had to be removed because of infection or obstruction over the follow-up period, although no prophylactic antibiotic agent was used. Restrictive use of antibiotics may prevent opportunistic infection. Frequent access to the device was significantly associated with line infection (odds ratio=8.43). No risk factor was identified for obstruction which occurred at a rate of 5.3 per 10,000 accesses.

INTRODUCTION: Central nervous system prophylaxis of childhood acute lymphoblastic leukemia has dropped rates of relapses but has been associated with neurotoxicity and imaging abnormalities. Predictors of neurotoxicity are lacking, because of inconsistency between clinical symptoms and imaging. Some have suggested that cerebrospinal fluid myelin basic protein (MBP) levels to be of potential interest. A retrospective analysis of MBP levels in correlation with clinical and radiologic data is presented. MATERIALS AND METHODS: MBP levels obtained at the time of intrathecals, charts, and neuroradiology reports were retrospectively analyzed. Academic achievement data were obtained from phone contacts with patients and families. RESULTS: We retrieved 1248 dosages of MBP in 83 patients, 381 neurologic examinations in 34 patients and 69 neuroradiologic investigations in 27 patients. Fifty-two patients had abnormal MBP levels. Radiologic anomalies were present in 47% of those investigated, 14% of them having school difficulties. Proportions of patients with school difficulties in the groups with abnormal MBP levels but no radiologic anomalies or with no radiologic investigations were 0% and 3%, respectively, which was lower than in the group of patients with normal MBP levels (100%, 22%, and 5%, respectively). DISCUSSION: Notwithstanding the retrospective character of our study, we conclude that there is limited usefulness of systematic dosage of MBP as indicator of treatment-induced neurotoxicity in acute lymphoblastic leukemia patients.

Background Sevelamer is a phosphate-binder used effectively for the treatment of hyperphosphatemia in patients treated with dialysis. Objectives To describe the safety of sevelamer in children with hyperphosphatemia secondary to tumor lysis syndrome and the serum phosphate concentrations observed following its administration. Procedure A retrospective chart review of all children with leukemia/lymphoma diagnosed between November 2002 and April 2004 who received sevelamer during their initial admission was conducted. We monitored the effects of sevelamer on serum phosphate concentration, calcium/phosphate product and renal function at hours 24, 48, and 72 from sevelamer initiation. Results Thirteen patients received sevelamer during the study period. Their median age was 13 years (range 2.7–17.9) and eight were boys. Nine children had acute lymphoblastic leukemia, one had acute myeloid leukemia and 3 had non-Hodgkin's lymphoma. The most frequently used dose of sevelamer was 400 mg orally twice daily. The median duration of sevelamer therapy was 2 days (range 1–7). Two children were excluded from the efficacy analysis due to concurrent use of dialysis. Mean serum phosphate levels decreased after sevelamer administration, in eleven patients, from a baseline 2.2 mmol/L ± 0.4 (95% CI, 1.7–3.1) to 1.1 mmol/L ± 0.2 at hour 72 (95%CI, 0.6–1.5). The only toxicity attributed to sevelamer was mild vomiting in three patients. Conclusions Sevelamer appears to be effective and tolerable for the treatment of hyperphosphatemia associated with tumor lysis syndrome. Pediatr Blood Cancer 2008;51:59–61. © 2008 Wiley-Liss, Inc.