Mode of administration of glucocorticoids and osteonecrosis in children treated for acute lymphoblastic leukemia: An update

peer reviewedEn tant que tumeur pédiatrique la plus fréquente, de surcroît grevée d’un excellent pronostic global, la leucémie lymphoblastique aiguë (LAL) représente la plus grande pourvoyeuse de survivants exposés à la toxicité des traitements chimiothérapeutiques. L’ostéonécrose est une complication bien décrite du traitement de la leucémie touchant jusqu’à un enfant sur dix, avec un tropisme particulier pour les adolescents atteints de leucémie à haut risque. Cette complication est liée à l’emploi des corticoïdes, dont la toxicité osseuse est potentialisée par l’emploi d’autres molécules, telles l’asparaginase et le méthotrexate. L’incidence de cette complication est plus élevée chez les patients recevant la dexaméthasone à titre de corticoïde principal. De récents protocoles thérapeutiques ont adopté, dans le but de réduire l’incidence de l’ostéonécrose, l’usage du schéma thérapeutique baptisé « split dexamethasone », une initiative du Children's Oncology Group (COG) consistant à marquer une pause de quelques jours dans l’administration de la dexaméthasone lors de la phase de réintensification. À ce jour, seuls un modèle animal et deux essais randomisés contrôlés du COG ont évalué l’intérêt de cette pratique. Ces derniers mettent en évidence un bénéfice de la méthode, avec une réduction de l’incidence d’ostéonécrose à 5 ans de l’ordre de 50 % pour le CCG 1961 et de 33 % chez les patients entre 10 et 12 ans pour le AALL0232, sans modification de la survie sans événement à 5 ans (EFS-5), qui reste de l’ordre de 75 % chez ces patients à haut risque. En conclusion, la prévention de l’apparition des lésions d’ostéonécrose via des amendements thérapeutiques, tel le « split dexamethasone » est non seulement réalisable et efficace, mais semble également sans danger sur le plan pronostic

Schizencephaly associated with a severe prothrombotic syndrome caused by antithombin III deficiency

peer reviewedaudience: professional, studen

Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma

Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature

Concomitant nodal involvement by Langerhans Cell Histiocytosis and Hodgkin Lymphoma

Introduction : Langerhans cell histiocytosis is defined as a clonal neoplastic proliferation of myeloid dendritic cells that upon activation migrate from the mucosal to lymph nodes. Definitive diagnosis is made by anatomo-pathological and immunohistochemical analysis. Langerhans cell histiocytosis is rarely, yet not exceptionally, found coexisting with other malignant neoplasms, suggesting it might arise in reaction to the cytokinic secretion of malignant cells. Case : We report the case of a 10-year-old female presenting with an isolated laterocervical lymphadenopathy and a mild general condition alteration tracing back to two months earlier. Nodal biopsy was performed and revealed concomitant involvement by Langerhans cell histiocytosis and Hodgkin lymphoma. Treatment of lymphoma led to the disappearance of the whole symptomatology. Discussion : Literature beholds reports of 30 cases of the simultaneous occurence of Hodgkin lymphoma with Langerhans cell histiocytosis, which is more than fortuitous regarding the low incidence of both diseases. A common etiology could explain such an association, but it might also be possible that background inflammatory cells of Hodgkin lymphoma stimulate the proliferation of Langerhans cells, making it a reactive process when occurring simultaneously with other neoplasms. Clinicians should thus be aware of the possibility of this association and carefully exclude any other life-threatening malignant proliferation when confronted to apparently isolated Langerhans cell histiocytosis