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To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT).We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units.From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P.0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.

BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders.The objectives are to describe the risk factors and the course of LE, and to investigate its impact on long-term neurocognitive and behavioural outcome. METHODS: A French retrospective, multicenter study including 35 children under 5 years of age, treated between 2009 and 2017, with a median follow up of 72 months. All follow-up MRIs including assessment of the severity of the LE (Fazekas and CTCAE grading) and all NP evaluations were centrally rewieved. RESULTS: 25/34 evaluable patients presented a LE during follow up, in a median delay of 2 months (1 - 17 months) after the start of chemotherapy. Grade 2 and 3 abnormalities were correlated with higher cumulative dose of ITV -MTX (p=0,01). Full Scale IQ (FSIQ) and Wechsler indexes were in the average or low average of the reference population. FSIQ was deficient in 7/20 evaluable patients. Processing speed (PSI) was the most frequently impaired neurocognitive domain: 9/20 patients with borderline or very low score, all having received a significantly higher cumulative dose of ITV-MTX (p=0,04). A decrease in overall NP scores was observed in patients for whom grade 2 or 3 LE persisted at the end of follow-up with an average FSIQ estimated at 82.1 (SD 16.9) versus 94.2 (SD 20.6). This decrease was significant for PSI (p=0,049). LE and neurocognitive impairments were not correlated with a younger age at diagnosis. CONCLUSION: This study confirmed the responsibility of MTX, and in particular ITV-MTX therapy in the onset and, most often, persistence of LE and its association with neurocognitive disorders.

International audience; Introduction: Our objectives were to assess the quality of life (QoL) of parents of childhood leukemia survivors compared with population norms and to identify the determinants of parents' long-term QoL.Methods: Parents of minors who had survived childhood leukemia participating in the French LEA cohort (Leucémie de l'Enfant et de l'Adolescent-French Childhood Cancer Survivor Study for Leukemia) were asked to complete the French version of the WHOQOL-BREF. Results were compared with age- and sex-matched values from a French reference population. Parents' and survivors' characteristics likely to be associated with QoL, long after the child's leukemia diagnosis, were explored using multivariate analysis.Results: We included 487 parents (mean age 42.9 ± 6.0 years, mean follow-up time from diagnosis 7.3 ± 3.3 years). Compared with the reference population, scores for physical health and social relationships for parents of childhood leukemia survivors were significantly lower (P < 0.001, effect size = 0.24 and P < 0.001, effect size = 0.29, respectively) contrary to scores for psychological health which were significantly higher (P < 0.001, effect size = 0.29). Even if health- and cancer-related characteristics were associated with parents' QoL in some dimensions, the only factor associated with each of the three dimensions (social relationships, physical health, and psychological) in the multivariate analysis was the parent's financial situation.Conclusions: Long after leukemia diagnosis, the parents reported lower scores in the physical health and social relationship domains. Despite the difficulties of actually influencing socioeconomic characteristics, it is important to consider the social situation of each family in the long-term care of survivors and their families.

Oncologic management in pediatric patient may be associated with a high risk of neurosensory deficit, such as taste, olfaction, vision and hearing. These neurosensory deficits can be linked to chemotherapy toxicity or to a direct deleterious effect of local radiotherapy or surgical management in case of craniofacial cancers. Neurosensory deficit may be temporary but are usually irreversible and frequently progress after the completion of treatment. Taste and olfaction deficits expose to high risk of nutritional complications and quality of life alteration. Hyposialia, as a result of irradiation of the salivary glands, increases taste changes and the risk of dental caries. The risk of cataract is present in patients who received high dose corticosteroids and/or brain or orbital irradiation. When hearing is affected, a risk of impaired intellectual or academic performance is increased with an impact on the quality of life in absence of specific care. Finally, there are some cosmetic consequences of therapy such as alopecia and scarring that alter the image of the patient. Early detection of these problems in order to limit medical, psychological, educational and social impact is mandatory. Moreover, high risk of worsening of these deficits after completion of therapy support long-term follow-up children treated for cancer, especially with head and neck primary.

International audience; Background: Although survival from childhood cancer has increased, ă little is known on the long-term impact of treatment late effects on ă occupational attainment or work ability. ă Methods: A total of 3512 five-year survivors treated before the age of ă 19 years in 10 French cancer centres between 1948 and 2000 were ă identified. Educational level, employment status and occupational class ă of survivors were assessed by a self-reported questionnaire. These ă outcome measures were compared with sex-age rates recorded in the French ă population, using indirect standardisation. Paternal occupational class ă was also considered to control for the role of survivors' socioeconomic ă background on their achievement. Multivariable analyses were conducted ă to explore clinical characteristics associated with the outcomes. ă Results: A total of 2406 survivors responded to the questionnaire and ă survivors aged below 25 years were included in the current analysis. ă Compared with national statistics adjusted on age and sex, male ă survivors were more likely to be college graduates (39.2% vs 30.9% ă expected; P

International audience; Late cardiomyopathy in childhood acute myeloid leukemia survivors: a study from the L.E.A. program Prognosis of pediatric acute myeloid leukemia (AML) has improved significantly over the past two decades with survival rates now approaching 70%. 1 Therapy consists of a limited number of intensive chemotherapy courses mainly based on cytarabine and anthracycline. 2,3 Many pediatric late anthracycline cardiotoxicity studies have concerned heterogeneous diagnostic groups. Moreover, single childhood cancer studies were mainly conducted in acute lym-phoblastic leukemia, whereas the highest doses of anthra-cycline are given in children with AML. 4-6 We report here a prospective multi-centric study of late cardiotoxicity in 185 patients surviving childhood AML. All were treated after 1989 in French clinical trials using intensive chemotherapy alone or chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). L.E.A. (Leucémie Enfant & Adolescent) is a French prospective long-term follow-up program involving all childhood acute leukemia survivors treated in the participating centers since 1980. Details of the programm are provided elsewhere. 7 As of 31 December 2011, 282 childhood AML survivors fulfilled the L.E.A. inclusion criteria and 218 (77.3%) of them agreed to participate. Among these 218, 185 were treated according to one of the 6 multicenter trial protocols ongoing in France after January 1989. All 185 had serial echocardiographic examination as part of their L.E.A. program, and all were included in the present study. All provided written informed consent. Cardiotoxicity was defined by either clinical symptoms of congestive heart failure or by an abnormal echocardiographic left ventricular function. Left ventricular function was considered abnormal when the shortening fraction (SF) was less than 28% or when the left ventricular ejection fraction (LVEF) was less than 55% on 2D echocardiography. 8-10 Cardiotoxicity was classified as late when it started or persisted beyond one year after the completion of first-line treatment. 9 Cumulative anthracycline doses used in each trial are described in the Online Supplementary Table S1, as well as the doxorubicin-equivalent doses using conversion factors of 0.83, 4.0 and 5.0 for daunorubicin, mitoxantrone and idarubicin, respectively. 10,11 Assessment of health status, long-term late effects on health-related quality of life (QoL), and statistical analysis are described in the Online Supplementary Appendix. Characteristics of the study cohort are summarized in Table 1. Median age at the time of AML diagnosis and median follow-up duration to last cardiac evaluation were 6.53 and 9.5 years, respectively. Thirty-seven patients had a history of relapse. Median cumulative anthracycline dose was 372 mg/m² (Online Supplementary Figure S1). Ninety-nine patients were treated by chemotherapy alone, whereas the other 86 patients also received HSCT (57 in first remission, 25 in second remission, and 4 in more advanced disease). Thirty children received total body irradiation (TBI), but only 10 among the 57 transplanted in first remission did so. Median number of echographic evaluations was 3 per patient. Subclinical cardiotoxicity (SCC) was observed in 23 of 185 patients (12.4%) at least once during their follow-up program. Median time from AML diagnosis to SCC detection was 4.40 years. In these 23 patients, the median value of the worst SF was 27% and the median value of the worst LVEF was 52. Only 3 of 23 patients had a worse SF value of less than 25% (2 had 20%; 1 had 24%). Six of 23 received anti-congestive therapy and none had cardiac transplantation. Five of those receiving anti-congestive therapy were still being treated at time of last evaluation, and 4 had more than 28% SF and more than 55% LVEF. Seventeen patients never received treatment: 11 had spontaneous improvement with more than 28% SF and more than 55% LVEF at last evaluation. Finally, at last cardiac evaluation, only 8 patients had an abnormal left ventricular function. Cumulative incidence (CI) of cardiotoxicity, estimated by the Kaplan-Meier method was 16% and 27% at 10 and 15 years, respectively (Figure 1A). CI of anti-conges-tive treatment at the same follow-up times was 5% and 7%. The risk of developing cardiotoxicity depended on a previous history of relapse and on the cumulative anthracy-cline dose. At ten years from diagnosis, CI was 35% versus 11% in patients with or without history of relapse (P=0.02) (Figure 1B). Among 148 patients without any history of relapse, 10-year CI of cardiotoxicity was 14% in 97 patients treated with chemotherapy alone versus 8% in 51 patients who underwent HSCT in first remission (NS, Figure 1C). In transplanted children, the risk was not modified by either a grade 2-4 acute or an extensive chronic graft-versus-host disease. The CI of anti-congestive treatment in these 148 patients who never experienced relapse was 3% at ten and

Oncologic management in pediatric patient may be associated with a high risk of neurosensory deficit, such as taste, olfaction, vision and hearing. These neurosensory deficits can be linked to chemotherapy toxicity or to a direct deleterious effect of local radiotherapy or surgical management in case of craniofacial cancers. Neurosensory deficit may be temporary but are usually irreversible and frequently progress after the completion of treatment. Taste and olfaction deficits expose to high risk of nutritional complications and quality of life alteration. Hyposialia, as a result of irradiation of the salivary glands, increases taste changes and the risk of dental caries. The risk of cataract is present in patients who received high dose corticosteroids and/or brain or orbital irradiation. When hearing is affected, a risk of impaired intellectual or academic performance is increased with an impact on the quality of life in absence of specific care. Finally, there are some cosmetic consequences of therapy such as alopecia and scarring that alter the image of the patient. Early detection of these problems in order to limit medical, psychological, educational and social impact is mandatory. Moreover, high risk of worsening of these deficits after completion of therapy support long-term follow-up children treated for cancer, especially with head and neck primary.

International audience; The main aim of the Leucémies de l'Enfant et l'Adolescent (LEA) project (Childhood and Adolescent Leukaemia) is to study the determinants (medical, socioeconomic, behavioural and environmental) of medium- and long-term outcomes of patients treated for childhood acute leukaemia (AL). The LEA study began in 2004 and is based on a French multicentric prospective cohort. Included are children treated for AL since January 1980 (incident and prevalent cases), surviving at month 24 for myeloblastic AL and lymphoblastic AL grafted in first complete remission or at month 48 for lymphoblastic AL not grafted in first complete remission. Information is collected during specific medical visits and notably includes the following data: socioeconomic data, AL history, physical late effects (such as fertility, cardiac function and metabolic syndrome) and quality of life. Data are collected every 2 years until the patient is 20 years old and has had a 10-year follow-up duration from diagnosis or last relapse. Thereafter, assessments are planned every 4 years. In active centres in 2013, eligible patients number more than 3000. The cohort has already included 2385 survivors, with rate of exhaustiveness of almost 80%. Data access can be requested from principal coordinators and must be approved by the steering committee.

Introduction Une sante degradee pendant l’enfance ou l’adolescence, parce qu’elle peut avoir un impact sur la reussite scolaire ou les strategies educatives, peut reduire les chances de mobilite sociale et peut, par consequent, contribuer a la formation des inegalites sociales de sante. Cependant, les etudes tendent a confondre les pathologies, rendant difficile l’exploration des mecanismes a l’œuvre. Nous proposons d’etudier ici le cas des cancers de l’enfant et de l’adolescent au travers d’une recherche a methodes mixtes. Methodologie Le volet quantitatif repose sur les resultats d’une cohorte retrospective de 2406 adultes traites avant l’âge de 18 ans pour une tumeur solide, entre 1948 et 1985, dans cinq centres francais. La position sociale de ces anciens malades a ete comparee a celle attendue dans une cohorte de meme âge et de meme sexe, en s’appuyant sur des statistiques de la population generale francaise. Parallelement, des entretiens approfondis ont ete menes aupres de 80 membres de la cohorte, selectionnes de maniere aleatoire. Resultats L’analyse des donnees de la cohorte montre que les survivants d’un cancer pediatrique ont une position sociale plus elevee que celle attendue, a l’exception des personnes traitees pour des tumeurs cerebrales. L’analyse de leur mobilite sociale intergenerationnelle, prenant en compte leur origine sociale, montre egalement une mobilite ascendante superieure a celle attendue. L’etude qualitative met en relief des mecanismes d’ascension sociale passant par des choix scolaires et professionnels qui se declinent differemment selon le genre. En particulier, les hommes disent avoir renonce a des carrieres trop physiques, souvent situees au bas de l’echelle sociale, en raison d’un handicap physique en lien avec la maladie, ou dans le but de preserver leur sante. Discussion Les resultats mettent en relief des mecanismes negatifs de selection par la sante.