Lymphomes lymphoblastiques pré-B de l'enfant. (Aspects cliniques, biologiques et évolutifs)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Infections fongiques invasives et leucémie aiguë myéloblastique de l'enfant (à propos de 26 cas traités dans le protocole ELAM 02)

INTRODUCTION : Les infections fongiques invasives (IFI) sont des complications sérieuses de l'immunosuppression induite par les chimiothérapies. Elles sont à l'origine d'une morbidité et mortalité propre chez les enfants traités dans les services d'hémato-oncologie pédiatrique. L'incidence de ces complications est connue pour être particulièrement élevée chez les enfants traités pour une leucémie myéloblastique (LAM). PATIENTS ET METHODES : Dans cette étude rétrospective, multicentrique nous avons inclus tous les enfants qui ont développé une infection fongique invasive (répondant aux derniers critères EORTC/MSG) lors du traitement par chimiothérapie du protocole ELAM 02 de 2005 à 2011 afin d'en décrire les particularités. RESULTATS : Vingt-six cas d'IFI sont survenus soit une incidence d'IFI de 6,7 %. L'âge médian était de 12 ans et le sex-ratio de 1,36 (15 garçons, 11 filles). Il y avait 15 aspergilloses, 9 candidoses et 2 mucormycoses. Douze IFI étaient prouvées, 6 probables et 8 possibles. La majorité des infections est survenue lors des phases intensives de traitement et la localisation clinique la plus fréquente était pulmonaire. L'analyse comparative entre le groupe avec IFI et sans IFI n'a pas permis de dégager des facteurs de risque. Tous les enfants étaient traités par les nouveaux antifongiques et les schémas thérapeutiques ont été étudiés. Au terme de la période de suivi médiane de 34 mois dix patients étaient décédés. Parmi eux 2 décès étaient attribuables directement à l'IFI. Il n'y avait pas de différence significative en termes de survie globale et sans événement entre le groupe avec IFI et sans IFI. DISCUSSION : Il existe maintenant des recommandations concernant la prise en charge des IFI en pédiatrie mais des études pédiatriques prospectives et multicentriques sont encore nécessaires afin d'améliorer les stratégies de prévention, de diagnostic précoce et de traitement des IFI dans cette population.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

The French FRACTURE database: A way to improve knowledge on management of children with very rare tumors

International audienceIntroduction: Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France. This study aims: (a) to describe the tumors registered in the FRACTURE database; and (b) to compare these data with those registered in the French National Registry of Childhood Cancer (RNCE).Methods: Data recorded in the FRACTURE database between January 1, 2012 and December 31, 2018 were analyzed. In addition, these data were compared with those of the RNCE database between 2012 and 2015 to evaluate the completeness of the documentation and understand any discrepancies.Results: A total of 477 patients with VRTs were registered in the FRACTURE database, representing 97 histological types. Of the 14 most common tumors registered in the RNCE (772 patients), only 19% were also registered in the FRACTURE database. Total 39% of children and adolescent VRTs registered in the RNCE and/or FRACTURE database (323 of a total of 828 patients) were not treated in or linked to a specialized pediatric oncology unit.Conclusion: VRTs represent many different heterogenous entities, which nevertheless account for 10% of all pediatric cancers diagnosed each year. Sustainability in the collection of these rare tumor cases is therefore important, and a regular systematic collaboration between the FRACTURE database and the RNCE register helps to provide a more exhaustive picture of these VRTs and allow research completeness for some peculiar groups of patients

Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study

International audienceBACKGROUND:In most countries, reference chemotherapy for osteosarcoma is MAP regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France, the standard preoperative chemotherapy for children/adolescents combines M and etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and efficacy results of patients ≤25 years treated with preoperative M-EI regimen enroled in the French OS2006-study, between 2007 and 2014.METHODS:Treatment comprised preoperative chemotherapy with the 7 M-courses and 2 EI-courses, then surgery and postoperative chemotherapy assigned by risk's groups: standard-risk (good histological response without metastases) received 12 M-courses, 3 EI-courses; high-risk (poor histologic response, initial metastases or unresectable primary) received 5 M-courses alternated with 5 AP-courses. 253 patients were randomised to receive (n = 128) or not (n = 125) zoledronate.RESULTS:409/522 patients enroled in the OS2006 study who received preoperative M-EI were analysed. Median age was 14.3 years (4.7-24.5), with 55 patients aged 18-25 years. Primary tumour location was limb in 383 patients (94%) and 85 (21%) presented metastases. Median chemotherapy duration was 37.4 weeks. 381 (96%) patients underwent surgery, 258 patients (65%) had a good histologic response. 187/324 patients (58%) with localised disease did not receive doxorubicin nor cisplatinum. Toxicity was evaluated in the randomised study: most patients experienced ≥1 severe toxicity (grade IV haematological or grade III/IV extra-haematological). Median follow-up was 4.8 years, and 168 patients had events. Five-year event-free survival was 56% (95% CI, 51-62%) and overall survival 71% (66-76%).CONCLUSION:M-EI regimen/strategy was feasible for patient aged ≤25 years with survival rates are comparable to those obtained with MAP regimen

Mutualisation des outils de qualité pour les cellules CAR-T : recommandations de la Société Francophone de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC)

Les cellules CAR-T sont des médicaments de thérapie anticancéreuse immunocellulaire impliquant la reprogrammation deslymphocytes T du patient à l'aide d'un transgène codant pour un récepteur antigénique chimérique (CAR). Bien qu'il s'agisse de thérapies cellulaires, les circuits de production et de délivrance sont bien différents de ceux des greffons de cellules hématopoïétiques ou de ceux desinjections de lymphocytes du donneur, notamment en raison de leur statut de médicament. La mise en œuvre de cette thérapie innovante est récente et nécessite une coordination étroite entre les équipes cliniques, l'unité d'aphérèse thérapeutique, la thérapie cellulaire, le laboratoire pharmaceutique, et la pharmacie. En dehors des textes réglementaires, qui sont régulièrement modifiés, et des exigences spécifiques de chaque laboratoire pharmaceutique, il n'existe pas actuellement de guide pour aider les centres à démarrer leur activité ni d'indicateurs spécifiques pour évaluer la qualité de l'activité CAR-T dans chaque centre. Cet atelier a pour buts de clarifier les prérequis réglementaires nécessaires pour qu'un centre ait une activité CAR-T et de proposer des recommandations pour mettre en place des outils de qualité, notamment des indicateurs, et permettre leur mutualisation

Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus : A Model of International Cooperation for Highly Specialized Treatments

Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. Methods and Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability