EJC paediatric oncology最新文献

{"title":"Assessing patient-reported outcomes (PROs) in paediatric oncology research: Which PRO would a pro pick, if a pro was picking PROs?","authors":"Ameeta Retzer ,&nbsp;Sarah Al-Jilaihawi ,&nbsp;Shivani Bailey ,&nbsp;Vickie Buenger ,&nbsp;Sarah Damery ,&nbsp;Anne-Sophie Darlington ,&nbsp;Manuel Diezi ,&nbsp;John Devin Peipert ,&nbsp;Jessica Roydhouse ,&nbsp;Bryce B. Reeve","doi":"10.1016/j.ejcped.2025.100232","DOIUrl":"10.1016/j.ejcped.2025.100232","url":null,"abstract":"<div><div>Patient-reported outcomes (PROs) enable the report of experiences that are only known to the patient, such as how an individual’s symptoms, functioning, and quality of life are impacted by a health condition or treatment. The choice of PRO depends on the intended application and associated research questions, and structuring a rationale for the use of PRO data is key to deciding upon a PRO strategy. Rates of PRO use in paediatric oncology research remain low though the general use of PROs in clinical trials has been gradually increasing. This is likely to have risen due to increased emphasis by regulatory agencies to capture outcomes meaningful to patients. Despite increasing interest in PROs, a range of barriers to their use have been identified by researchers exploring their implementation and a pattern of under-reporting of PRO data has also been observed in general oncology trials. Research with children entails specific challenges, including the need for developmentally-appropriate outcome measures, the complexities of family involvement, and the adaptations required in research procedures and settings to accommodate children's physical, cognitive, and emotional development. With the nascent use of PROs in paediatric oncology, there are opportunities to benefit from learning from trials involving adult participants. The current paper outlines considerations for PRO selection for use in paediatric oncology research, describing five steps to determine the PRO study goals, the study outcomes, the reporter(s), measures, and study implementation. We discuss the breadth of applications of PROs in paediatric oncology research and potential for further learning and harmonisation with the aim of centering children’s experiences.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100232"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of genes by MYCN in PAX3::FOXO1-positive rhabdomyosarcomas and their roles in cell cycle progression","authors":"Zoë S. Walters ,&nbsp;Daniel Leongamornlert ,&nbsp;Barbara Villarejo-Balcells ,&nbsp;Carmen Tse ,&nbsp;Reuben Pengelly ,&nbsp;Ian Titley ,&nbsp;Janet Shipley","doi":"10.1016/j.ejcped.2025.100230","DOIUrl":"10.1016/j.ejcped.2025.100230","url":null,"abstract":"<div><h3>Background</h3><div><em>MYCN</em> amplification and high expression is associated with pediatric malignancies including neuroblastoma and alveolar rhabdomyosarcoma. <em>MYCN</em> transcription in alveolar rhabdomyosarcomas is driven by a feedback loop with the PAX3::FOXO1 fusion protein. However, the role of MYCN is not well-defined.</div></div><div><h3>Methods</h3><div>Chromatin ImmunoPrecipitation (ChIP)-sequencing of alveolar rhabdomyosarcoma cell lines was used to identify genome-wide MYCN binding sites. Ontology analyses of genes adjacent to MYCN binding sites corresponding to expression changes after siRNA reduction was performed and confirmed by ChIP-qPCR. Cells from each phase of the cell cycle were isolated by Fluorescence Activated Cell Sorting for assessing protein expression by Western blotting.</div></div><div><h3>Results</h3><div>Genes encoding transcription factors adjacent to MYCN binding sites and genes with binding sites proximal to their promoters were strongly associated with RNA synthesis and cell cycle pathways, respectively. MYCN binding sites in regions that positively correlated with gene expression changes were linked to cell cycle regulation, consistent with phenotypic absence of cell cycle checkpoint control. Cell cycle regulated genes <em>CDK4</em> and <em>KDM4B</em> were validated as MYCN-regulated and, in-keeping with unchecked cell cycle progression, expressed throughout the cell cycle, coincident with MYCN.</div></div><div><h3>Conclusions</h3><div>MYCN binding sites associated with gene expression changes defined the contribution of MYCN to the transcriptional control of key pathways/molecular processes in the development and progression of rhabdomyosarcomas. MYCN aberrantly regulated <em>CDK4</em> and <em>KDM4B</em> expression throughout the cell cycle in <em>PAX3::FOXO1</em> positive rhabdomyosarcoma. The regulatory network defined supports MYCN, CDK4 and KDM4B as therapeutic targets in the treatment of rhabdomyosarcoma patients.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100230"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European standard clinical practice recommendations for children and adolescents with Rhabdomyosarcoma a joint EpSSG, CWS and ERN PaedCan project","authors":"Johannes H.M. Merks ,&nbsp;Eva Brack ,&nbsp;Martin Ebinger ,&nbsp;Véronique Minard-Colin ,&nbsp;Anne-Sophie Defachelles ,&nbsp;Raquel Hladun ,&nbsp;Timothy Rogers ,&nbsp;Jörg Fuchs ,&nbsp;Jan Godzinski ,&nbsp;Sheila Terwisscha van Scheltinga ,&nbsp;Gabriela Guillén Burrieza ,&nbsp;Henry Mandeville ,&nbsp;Beate Timmermann ,&nbsp;Raquel Davila Fajardo ,&nbsp;Rick R. van Rijn ,&nbsp;Jürgen Schäfer ,&nbsp;Helen Rees ,&nbsp;Andrea Ferrari ,&nbsp;Rita Alaggio ,&nbsp;Anna Kelsey ,&nbsp;Gianni Bisogno","doi":"10.1016/j.ejcped.2025.100229","DOIUrl":"10.1016/j.ejcped.2025.100229","url":null,"abstract":"<div><div>Rhabdomyosarcoma (RMS) is a heterogeneous group of malignancies with specific histopathological characteristics. Distinct molecular findings help to classify RMS into PAX::FOXO1 fusion gene positive and fusion gene negative subtypes. Further new molecular subtypes give insight into the heterogeneity of these rare tumours. Multiple international clinical trials have been conducted to improve the prognosis for paediatric, adolescent, and young adult patients with RMS. The overall cure rate is around 70 % but varies dramatically between the low risk localised and very high-risk metastatic patients. New treatment approaches are needed in the High-Risk and Very High-Risk RMS disease to improve patients’ outcome. State of the art diagnostics and staging is crucial and the multimodal treatment approach in specialized paediatric-oncology centres is highly recommended. Treatment includes chemotherapy with vincristine, actinomycin, and ifosfamide with or without anthracyclines. Local treatment with the aim of microscopically complete resection and/or radiotherapy is warranted depending on patient and tumour characteristics. Maintenance treatment is recommended to (Very) High Risk groups. This consensus summarizes the standard of care diagnostic work up, multimodal treatment and surveillance recommendations for paediatric, adolescent, and young adult patients with RMS. The guideline was developed as a joint project by the European <em>paediatric</em> Soft tissue sarcoma Study Group (E<em>p</em>SSG) and the Cooperative Weichteilsarkom Studiengruppe (CWS) summarized as the European RMS working group supported by European Reference Network on Paediatric Cancer (ERN PaedCan).</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European standard clinical practice recommendations for newly diagnosed ependymoma of childhood and adolescence","authors":"Alba Rubio-San-Simón ,&nbsp;Timothy A. Ritzmann ,&nbsp;Denise Obrecht-Sturm ,&nbsp;Martin Benesch ,&nbsp;Beate Timmermann ,&nbsp;Pierre Leblond ,&nbsp;John-Paul Kilday ,&nbsp;Geraldina Poggi ,&nbsp;Nicola Thorp ,&nbsp;Maura Massimino ,&nbsp;Marie-Lise van Veelen ,&nbsp;Martin Schuhmann ,&nbsp;Ulrich-Wilhelm Thomale ,&nbsp;Stephan Tippelt ,&nbsp;Ulrich Schüller ,&nbsp;Stefan Rutkowski ,&nbsp;Richard G. Grundy ,&nbsp;Stephanie Bolle ,&nbsp;Ana Fernández-Teijeiro ,&nbsp;Kristian W. Pajtler","doi":"10.1016/j.ejcped.2025.100227","DOIUrl":"10.1016/j.ejcped.2025.100227","url":null,"abstract":"<div><div>Ependymomas are tumors of glial origin representing the second most common malignant brain tumors of childhood. Peak incidence in childhood is under 3 years of age. Most paediatric ependymomas arise intracranially and are molecularly divided into four groups, namely supratentorial ependymoma, ZFTA fusion-positive (ST-ZFTA), supratentorial ependymoma, YAP1 fusion-positive (ST-YAP1), posterior fossa group A (PF-A), and posterior fossa group B (PF-B) ependymoma. Spinal ependymomas in children are rare. An integrated diagnosis requires a combination of histological and molecular features as well as tumour localization. Staging with pre- and early post-surgery magnetic resonance imaging of the neuraxis, accompanied by cerebrospinal fluid (CSF) analysis 14 days post surgery must be performed. CSF at primary surgery is highly recommended to both detect and inform biomarkers. Patients should ideally be treated in specialized centers and, whenever possible, within a prospective clinical trial. Molecular classification has become increasingly important and will be applied to enable patient stratification in upcoming clinical trials. However, there are not yet specific treatment recommendations for distinct molecular groups. Apart from the molecular group, the extent of neurosurgical resection is the most consistent prognostic factor. Therefore, the feasibility of second-look surgery targeting complete resection should always be evaluated if residual disease. Adjuvant radiotherapy has been shown to be effective in consolidating local control and is therefore recommended following complete resection. Focal radiotherapy is the standard of care for patients with non-disseminated ependymoma, and craniospinal radiotherapy is recommended in older children with metastatic disease. For very young children with metastatic disease, radiotherapy avoidance strategies using systemic therapy is recommended to reduce the risk of neurocognitive effects. Highly conformal techniques such as proton beam therapy or intensity-modulated radiation therapy are preferred. Chemotherapy bridging therapy may be applied until patients reach 12–18 months of age, or to facilitate complete resections where further surgery is planned.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100227"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy for paediatric diffuse large B-cell lymphoma: A review of current clinical trials and future directions","authors":"Anne van Kuijk ,&nbsp;Pamela Kearns ,&nbsp;G.A. Amos Burke","doi":"10.1016/j.ejcped.2025.100228","DOIUrl":"10.1016/j.ejcped.2025.100228","url":null,"abstract":"<div><div>Paediatric diffuse large B-cell lymphoma (DLBCL) is a rare but aggressive form of non-Hodgkin lymphoma. Although rituximab has significantly improved outcomes in both adult and paediatric patients, challenges remain for those who relapse or are resistant to the initial treatment. This review examines recent clinical trials investigating various immunotherapies for relapsed or refractory (R/R) paediatric DLBCL, including immunomodulatory agents, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T-cell therapy. A comprehensive search identified forty-eight relevant trials with significant focus on CAR-T cell therapy. This review highlights the potential benefits of these novel therapies for improving the survival rate and quality of life of paediatric patients. However, it also underscores the need for increased international collaboration and paediatric-specific research to address the unique challenges in treating this vulnerable population. Future directions include the integration of personalised medicine and development of chemotherapy-free regimens.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100228"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of the European standard clinical practice recommendations for choroid plexus tumours","authors":"David King ,&nbsp;Brigitte Bison ,&nbsp;Ofelia Cruz ,&nbsp;Claudia C. Faria ,&nbsp;Iwona Filipek ,&nbsp;Jonathan L. Finlay ,&nbsp;Miklós Garami ,&nbsp;Uwe R. Kordes ,&nbsp;Ulrike Löbel ,&nbsp;Jilly Maclean ,&nbsp;Torben Stamm Mikkelsen ,&nbsp;Denise Obrecht-Sturm ,&nbsp;Guirish Solanki ,&nbsp;Christian Thomas ,&nbsp;Beate Timmerman ,&nbsp;Michal Zapotocky ,&nbsp;Jenny Adamski","doi":"10.1016/j.ejcped.2025.100226","DOIUrl":"10.1016/j.ejcped.2025.100226","url":null,"abstract":"<div><div>Choroid plexus tumours (CPT) are rare epithelial brain tumours that primarily affect very young children. They can be classified as benign choroid plexus papilloma (CPP, WHO grade 1), intermediate grade atypical choroid plexus papilloma (aCPP, WHO grade 2) or highly malignant choroid plexus carcinoma (CPC, WHO grade 3). Treatment is dependent on tumour grade, surgical resection, the age of the child and somatic and germline <em>TP53</em> mutational status. CPP and aCPP have a good prognosis and are frequently curable with surgery alone. In contrast, the prognosis in CPC is often poor, despite intensive multimodal treatment with surgery, chemotherapy and radiotherapy. Management is complicated by the increased incidence of germline <em>TP53</em> mutations and cancer predisposition (Li-Fraumeni syndrome), especially in CPC, whilst the rarity of the diagnosis means there are a lack of robust clinical data on which to base treatment decisions. Studies generally comprise of retrospective, single arm and centre trials or case series, and patient numbers are small leading to conflicting results that are difficult to interpret. Standardised treatment protocols have historically been lacking.</div><div>The aim of this document is to provide a reference standard for the treatment of CPT on behalf of the European Society for Paediatric Oncology (SIOPE). We review the previously published literature and provide consensus key recommendations for the management of CPP, aCPP and CPC including surgical approaches and when appropriate, the role of chemotherapy and radiotherapy. Suggested follow-up and possible relapse strategies are also suggested.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100226"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curing using the minimal – Strategies for treatment reduction in childhood acute lymphoblastic leukemia","authors":"Bernice LZ Oh ,&nbsp;Stephen P. Hunger ,&nbsp;Allen EJ Yeoh ,&nbsp;Shawn HR Lee","doi":"10.1016/j.ejcped.2025.100222","DOIUrl":"10.1016/j.ejcped.2025.100222","url":null,"abstract":"<div><div>Childhood acute lymphoblastic leukemia (ALL) in the contemporary era of intensive chemotherapy is highly curable, but is associated with a plethora of toxicities, with persistent disparities in survival outcomes globally especially in low-middle income countries (LMIC). Because of limited supportive care in LMIC, treatment-related morbidity and mortality may be a more critical treatment factor than relapse. Therefore, the next frontier in childhood ALL is to cure low-risk ALL with as minimal therapy as possible. Here, we discuss how to identify the subset of low-risk patients for whom this is possible, along with the components of deintensification strategies across several regimens in recent clinical trials for low-risk ALL. In treating low-risk childhood ALL, the key is accurately identifying this curable subset. NCI standard-risk criteria at diagnosis (age 1–10 years, WBC &lt; 50,000/uL) remains an effective cornerstone of stratification. Other favorable features such as identifying low risk genetics (<em>ETV6</em>::<em>RUNX1</em>, hyperdiploidy), early peripheral blood and bone marrow responses, and simplified flow MRD at the end of induction can be added depending on resources to enhance stratification. A reduced intensity induction particularly through anthracycline-free induction, allows early marrow recovery and reduces the need for intensive supportive care. Other key effective deintensification strategies in low-toxicity protocols include: replacing high-dose with low-dose escalating methotrexate; judicious or even omission of anthracyclines throughout therapy; non-augmentation of consolidation therapy; reducing or even omitting delayed intensification; decreasing thiopurine or methotrexate doses during maintenance; and lowering intensity of steroid pulses during maintenance. Future directions include potential implementation of immunotherapy upfront to low-risk ALL, which may allow for even further reducing toxic chemotherapy or treatment duration. Overall, the first effective step in achieving global ALL cure is to focus on curing low-risk ALL through as minimal therapy as possible.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline","authors":"Miguel Vieira Martins ,&nbsp;Anna Sofie Buhl Rasmussen ,&nbsp;Jesper Heldrup ,&nbsp;Linea Natalie Toksvang ,&nbsp;Marianne Ifversen ,&nbsp;Stine Nygaard Nielsen ,&nbsp;Kjeld Schmiegelow ,&nbsp;Inge Margriet van der Sluis","doi":"10.1016/j.ejcped.2025.100225","DOIUrl":"10.1016/j.ejcped.2025.100225","url":null,"abstract":"<div><div>Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the <em>ALLTogether1</em>. The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity. Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply. Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes. Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness. This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment. Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100225"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for childhood cancer: Several devils in the details","authors":"Logan G. Spector,&nbsp;Erin L. Marcotte","doi":"10.1016/j.ejcped.2025.100224","DOIUrl":"10.1016/j.ejcped.2025.100224","url":null,"abstract":"","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100224"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGH rearrangements in Down syndrome acute lymphoblastic leukemia","authors":"Naomi Michels ,&nbsp;Jade Admiraal ,&nbsp;Aurélie Boeree ,&nbsp;Edwin Sonneveld ,&nbsp;Anthony V. Moorman ,&nbsp;Gabriele Escherich ,&nbsp;Rosemary Sutton ,&nbsp;H. Berna Beverloo ,&nbsp;Rob Pieters ,&nbsp;C. Michel Zwaan ,&nbsp;Monique L. den Boer ,&nbsp;Judith M. Boer","doi":"10.1016/j.ejcped.2025.100223","DOIUrl":"10.1016/j.ejcped.2025.100223","url":null,"abstract":"<div><h3>Background</h3><div>The <em>IGH</em> locus is susceptible to translocations or insertions that contribute to B-cell precursor acute lymphoblastic leukemia (ALL) by ectopic or enhanced expression of a gene relocated to the <em>IGH</em> enhancer. The frequency of <em>IGH</em> rearrangements is relatively high in Down syndrome (DS) ALL. <em>IGH</em> rearrangements can be cryptic and might not be detected as a chimeric transcript, hence, their frequency, partner genes and prognostic value are largely unknown.</div></div><div><h3>Methods</h3><div>We performed RNA-sequencing and <em>IGH</em> break-apart fluorescent in-situ hybridization (FISH) to determine the genetic and clinical characteristics of <em>IGH</em> rearrangements in 50 DS ALL patients.</div></div><div><h3>Results</h3><div>We identified 10 patients with a chimeric <em>IGH</em> transcript and another 22 <em>IGH-</em>rearranged patients solely by FISH. The <em>IGH</em> rearrangement was clonal (≥ 50 % of leukemic cells) in 11 cases and subclonal (10–50 % of cells) in 21 cases. Almost one-third of the subclonal <em>IGH</em> rearrangements co-occurred with known oncogenic driver aberration. The partner gene was identified in 16 cases and the most frequent partners were <em>CEBPD</em> (n = 6) and <em>CRLF2</em> (n = 4). A trend towards a worse event-free survival was seen for DS ALL patients with a clonal <em>IGH</em> rearrangement (clonal: HR 3.34, p = 0.053; subclonal: HR 1.80, p = 0.31) compared with DS ALL patients without an <em>IGH</em> rearrangement.</div></div><div><h3>Conclusion</h3><div>By combining RNA-sequencing and FISH, we identified <em>IGH</em> rearrangements in 64 % (n = 32) of DS ALL. A clonal <em>IGH</em> rearrangement (22 %) may point to an unfavorable outcome in DS ALL.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}