89 research outputs found
A French Cohort of Childhood Leukemia Survivors: Impact of Hematopoietic Stem Cell Transplantation on Health Status and Quality of Life
AbstractThe late effects and quality of life (QoL) in childhood acute leukemia survivors were compared between hematopoietic stem cell transplantation (HSCT) recipients and patients who underwent conventional therapy. The study included 943 patients, 256 of whom underwent HSCT (27.1%). Medical visits were conducted to detect the occurrence of physical late effects. Based on patient age, different questionnaires were used to assess QoL. To evaluate the association between HSCT and each type of late effect or QoL dimension, the appropriate multivariate regressions were performed. QoL mean scores were compared with those obtained for age- and sex-matched French control subjects. Of all the survivors, 674 (71.5%) had at least 1 late effect, with the risk being 5.0 CI95 (3.0-8.6) times higher for transplantation survivors. For child survivors, scoring of QoL showed no significant differences between the treatment groups. The adult HSCT survivors reported lower physical dimension QoL scores than chemotherapy survivors. Compared with French norms, the survivor group reported a significantly lower mental composite score; however, the physical composite score showed no significant difference. Thus, transplanted survivors have a high risk of developing late effects, resulting in a decreased physical well-being in adulthood. However, long after treatment completion, childhood leukemia survivors report that effects on psychological well-being are more important than they are in physical QoL dimensions
Metronomic Four-Drug Regimen Has Anti-tumor Activity in Pediatric Low-Grade Glioma; The Results of a Phase II Clinical Trial
Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC has shown its efficacy in adult tumor types such as breast and ovarian cancer and has to some extent been studied in pediatrics.Objective: To assess the anti-tumor activity and toxicity of a four-drug metronomic regimen in relapsing/refractory pediatric brain tumors (BT) with progression-free survival (PFS) after two cycles as primary endpoint.Methods: Patients â„4 to 25 years of age were included with progressing BT. Treatment consisted of an 8-week cycle of celecoxib, vinblastine, and cyclophosphamide alternating with methotrexate. Kepner and Chang two-steps model was used with 10 patients in the first stage. If stabilization was observed in â„2 patients, 8 additional patients were recruited. Assessment was according WHO criteria with central radiology review.Results: Twenty-nine patients (27 evaluable) were included in two groups: ependymoma (group 1, N = 8), and miscellaneous BT (group 2): 3 medulloblastoma (MB), 5 high grade glioma (HGG), 11 low grade glioma (LGG), 2 other BT. After first stage, recruitment for ependymoma was closed [one patient had stable disease (SD) for 4 months]. Cohort 2 was opened for second stage since 1 HGG and 3 LGG patients had SD after two cycles. Recruitment was limited to LGG for the second stage and 2 partial responses (PR), 6 SD and 2 progressive disease (PD) were observed after two cycles. Of these patients with LGG, median age was 10 years, nine patients received vinblastine previously. Median number of cycles was 6.8 (range: 1â12). Treatment was interrupted in five patients for grade 3/4 toxicity.Conclusion: This regimen is active in patients with LGG, even if patients had previously received vinblastine. Toxicity is acceptable.Trial Registration: This study was registered under clinicaltrials.gov â NCT01285817; EUDRACT nr: 2010-021792-81
A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors
Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies
Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009
<p>Abstract</p> <p>Objective</p> <p>To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.</p> <p>Study design</p> <p>Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009.</p> <p>Results</p> <p>21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications.</p> <p>Conclusion</p> <p>Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.</p
Fertilité et grossesses des jeunes femmes traitées par radiothérapie abdomino-pelvienne dans leur enfance
Introduction : Une radiothĂ©rapie abdominale et/ou pelvienne rĂ©alisĂ©e pour un cancer dans l'enfance ou l'adolescence risque d'avoir ultĂ©rieurement des effets sur la fertilitĂ© et les grossesses. MatĂ©riel et mĂ©thodes : La pubertĂ© et le devenir des grossesses de filles traitĂ©es par une irradiation abdominale dans deux centres (Nancy et Lyon), entre 1975 et 2004 ont Ă©tĂ© analysĂ©s rĂ©trospectivement. L'analyse du dossier mĂ©dical, des dosimĂ©tries et d'un questionnaire concernant menstruations et grossesses, a permis le recueil des informations. RĂ©sultats : Quatre-vingt-quatre patientes ont reçu une irradiation abdominale, sont en vie et ont plus de 18 ans en 2007. Parmi 57 patientes traitĂ©e par irradiation uniquement abdominale, 52 (90%) ont Ă©tĂ© rĂ©glĂ©es spontanĂ©ment et 23 (40%) ont eu au moins une grossesse. Parmi 27 filles traitĂ©es par une irradiation incluant le pelvis, seules 10 (37%) ont prĂ©sentĂ© des menstruations spontanĂ©es et 5 (19%) ont eu au moins une grossesse. Vingt-deux femmes (17 aprĂšs une irradiation pelvienne), apparaissent difficilement fertiles : 8 jamais rĂ©glĂ©es, 11 uniquement par un traitement hormonal (dont 3 n'ont pas obtenu une grossesse dĂ©sirĂ©e), 3 rĂ©glĂ©es spontanĂ©ment mais n'ayant jamais rĂ©ussi Ă ĂȘtre enceinte. Il y a eu 50 bĂ©bĂ©s de 28 mĂšres, un mort-nĂ© et 17 avortements spontanĂ©s. Il a Ă©tĂ© notĂ© une prĂ©valence Ă©levĂ©e de prĂ©maturĂ©s et d'hypotrophie <2500g) mais pas de malformations congĂ©nitales. La dose aux organes gĂ©nitaux est le facteur dĂ©terminant avec un seuil de risque bas Ă 4 Gy. Discussion et Conclusion : La fertilitĂ© fĂ©minine peut ĂȘtre prĂ©servĂ©e aprĂšs une irradiation abdominale. Elle peut ĂȘtre normale aprĂšs irradiation pelvienne, mais il est prĂ©fĂ©rable, si possible, de protĂ©ger les organes gĂ©nitaux. Un monitoring prolongĂ© est nĂ©cessaire pour toutes les filles traitĂ©es par une irradiation abdominale et/ou pelvienne.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
RÎle du type de décontamination digestive sur la survenue d'épisodes fébriles au cours du traitement d'induction des leucémies aiguës (étude rétrospective à propos de 145 cas)
Notre étude a pour but de mettre en évidence l'évolution de la flore fécale et des épisodes infectieux, notamment à point de départ digestif, dans une population d'enfants recevant la phase d'induction thérapeutique d'une leucémie aiguë dans le service d'onco-hématologie du CHU de Nancy de janvier 1995 à mai 2005. Elle a été motivée par le fait du changement des mesures de prévention vis-à -vis des infections réalisé depuis le mois de mai 2004, pour la population des leucémies aiguës lymphoblastiques : une décontamination digestive partielle par gentamicine et amphotéricine B orales, associée à un isolement protecteur et une alimentation pauvre en germes, a remplacé la décontamination digestive totale associée à un isolement et une alimentation " stériles ". Le but de ce changement était de restreindre le coût de la prise en charge de la séquence la plus onéreuse : le traitement d'induction. Le taux de décontamination sous DDT est de 99% et sous DDP de 82% (respectivement pour les germes bactériens et les bacilles à Gram négatif (BGN)). Dans les deux modes de prise en charge, la mortalité d'origine infectieuse est nulle et aucune translocation de BGN n'a été constatée. Une translocation de levures a été observée dans le groupe de la DDP.L'émergence d'un germe résistant à la gentamicine dans le groupe de la DDP nous incite à la plus grande prudence et entraßne la nécessité d'un suivi bactériologique hebdomadaire des selles pour surveiller l'efficacité de la prophylaxie et permettre une adaptation de celle-ci à l'antibiogramme des BGN identifiés.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Retard au diagnostic des tumeurs cérébrales de l'enfant et ses conséquences
Objectifs: Analyser les signes d'appel des tumeurs cĂ©rĂ©brales de l'enfant, relever les erreurs diagnostiques les plus frĂ©quentes, Ă©valuer le dĂ©lai diagnostique et son impact sur le pronostic: Etude rĂ©trospective descriptive, sur 354 enfants atteints de tumeur cĂ©rĂ©brale. Les donnĂ©es recueillies sont l'Ăąge, le sexe, la localisation tumorale, les premiers symptĂŽmes, les hypothĂšses diagnostiques, le dĂ©lai pour Ă©tablir le diagnostic et le devenir des patients. RĂ©sultats: L'Ăąge moyen au diagnostic est de 8,2 ans, le sex ratio de 1,19. Les symptĂŽmes initiaux les plus frĂ©quents sont des cĂ©phalĂ©es isolĂ©es, des signes francs d'hypertension intra- crĂąnienne, des convulsions ou des vomissements isolĂ©s. Les erreurs diagnostiques classiques sont les troubles psychogĂšnes, l'Ă©pilepsie essentielle et la migraine. Le dĂ©lai diagnostique moyen est de 5,9 mois, la mĂ©diane est de 1,75 mois. Son impact sur le pronostic vital n'est pas dĂ©montrĂ©. L'influence sur les sĂ©quelles neuro-cognitives n'est pas mis en Ă©vidence, mais une Ă©tude multi-factorielle et une Ă©valuation objective des patients sont encore nĂ©cessaires pour l'affirmer. Conclusion: Les tumeurs cĂ©rĂ©brales sont les cancers de l'enfant les moins bien diagnostiquĂ©s. Le retard au diagnostic est parmi les plus longs, avec une moyenne de prĂšs de 6 mois dans notre Ă©tude. Ce dĂ©lai pourrait ĂȘtre rĂ©duit par une meilleure reconnaissance des signes d'appel par les parents et les mĂ©decins. Une imagerie cĂ©rĂ©brale est en effet indiquĂ©e devant la persistance et/ou l'intensitĂ© de certains signes considĂ©rĂ©s Ă tort comme banals chez l'enfant. La morbiditĂ© associĂ©e Ă la prise en charge des tumeurs cĂ©rĂ©brales en serait probablement diminuĂ©e.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Impact du fractionnement du traitement sur les propriétés radiosensibilisantes du bortézomib sur deux modÚles de gliome malin humain xénogreffés
Les gliomes malins, tumeurs du systÚme nerveux central les plus fréquentes ont un pronostic particuliÚrement sombre. Parmi les traitements standards de ce type de tumeurs, la radiothérapie occupe une place prépondérante mais son utilisation est limitée en raison de la mauvaise tolérance du tissu cérébral normal. Une des stratégies visant à améliorer l efficacité de la radiothérapie consiste en l administration concomitante d un agent radiosensibilisant. Les inhibiteurs de protéasome sont une nouvelle classe d agents anticancéreux et le bortézomib (VelcadeŸ), chef de file de cette nouvelle classe, possÚde une AMM dans le traitement du myélome multiple. Les objectifs de nos travaux sont d évaluer le potentiel radiosensibilisant du bortézomib sur deux modÚles de gliome malin humain xénogreffés chez la souris nude. Nous avons apporté une attention particuliÚre à l impact du fractionnement du bortézomib et de la radiothérapie sur l efficacité antitumorale de l association. Nos résultats montrent que le bortézomib est un radiosensibilisant puissant sur les deux modÚles de gliome malin utilisés mais que ce pouvoir est perdu lorsque les deux modalités thérapeutiques sont délivrées selon des doses et des schémas d administration pertinents au regard de la clinique. En condition de traitement fractionné, nos études montrent également que le bortézomib induit une diminution de l apoptose radio-induit, probablement en lien avec une perte de son activité inhibitrice du protéasome au fil des injections. Enfin, la place du facteur de transcription NF-?B dans la réponse à la radiothérapie fractionnée ou non pour le type tumoral que nous avons étudié est discutée. En conclusion, nos travaux insistent sur la nécessité de réaliser des études précliniques dans des conditions les plus proches possibles de la situation clinique, afin d apporter des éléments plus prédictifs de la réponse chez l Homme.Malignant gliomas are the most common neoplasm of the central nervous system and patients prognosis remains dismal, despite aggressive surgery, radio- and chemotherapy. Radiotherapy is a major treatment modality in this tumoral type but its usefulness is limited by normal brain tissue toxicity. The concomitant administration of a radiosensitizing agent is an innovative strategy to improve ionizing radiations efficacy. Bortezomib (VelcadeŸ) belongs to a new class of anticancer agents, i.e. the proteasome inhibitors, and this molecule has been approved for the treatment of multiple myeloma. Our objectives are to study the radiosensitizing properties of bortezomib on two human malignant glioma models xenografted onto nude mice. Our work was designed to evaluate the impact of treatment fractionation on the antitumor activity of the concomitant association of bortezomib and radiotherapy. Our results show that bortezomib is a potent radiosensitizer on our two malignant glioma models but these properties are lost when treatments are fractionated according to a typical clinical schedule. In conditions of fractionated treatment, we demonstrate that bortezomib reduces the radio-induced apoptosis. This may be linked to the loss of the inhibitory properties of bortezomib secondary to consecutive infusions. We also evaluate the importance of the transcription factor NF-?B in the radioresponse of the malignant glioma xenografts used. Finally, our work emphasizes on the importance of performing preclinical studies using doses and therapeutic schedule mimicking the clinical settings to provide more predictive results of treatment response in Humans.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF
Quality of life in pediatric cancer survivors : A new contribution including goal concept
International audienceThe present study focuses on quality of life in children survivors of cancerthrough the filter of self-regulation by goals. In this respect, the model of Dupuis and its operationalization by Missotten through the Child Quality of Life Systemic Inventory (QLSI-C©) makes it possible to identify the regulation processes (state, goal, speed, rank), in order to distinguish between children survivors of cancer and their healthypeers, as well as identifying the impact of these processes on anxiety and depression symptoms. Fifty children survivors of cancer,aged 8 to 12 years, answered three questionnaires: the QLSI-C©, the State-Trait Anxiety Inventory â Child (STAI-C), and the Child Depression Inventory (CDI). Their responses were compared with those obtained from 50 healthychildrenof the same age. Partial Least Squares Discriminant Analysis (PLS-DA) was used to show that the process that best differentiated the two groups pointed to a regulation through goals and priorities. Results revealed too that these processes were particularly apparent in 8 of the 20 life domains examined. Moreover, of the four processes, state is the best predictor of depressive symptoms. Children survivors of cancerdo not view their lives and plans in the same manner as their healthy peers. However, their different strategies of regulating goals and priorities do not result in more depressive symptoms than in their healthy peers. The question of whether more demanding goals and priorities are necessarily a source of well-being remains to be determined
Long-term Adverse Effects of Acute Myeloid Leukemia Treatment on Odontogenesis in a Child
International audienc
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