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Rifhop is a pediatric oncology coordination center in the Île-de-France region, funded by the regional health agency. Its mission is to support children, adolescents, and their families throughout the entire course of care. It contributes to the training of healthcare professionals and the standardization of practices. To fulfill these missions, the network consists of a staff of five nurses, a pediatric nurse manager, and an assistant. This team serves as the link between the hospital and the home to streamline the patient's care journey as much as possible and support families during key milestones such as the first return home or the child or adolescent's return to school.
Differentiated thyroid carcinoma is the most common endocrine malignancy in children and typically presents as an isolated tumor. The synchronous occurrence of differentiated thyroid carcinoma with a second, non-thyroid primary malignancy is exceptionally rare and poorly characterized in pediatric patients. We reviewed 571 pediatric patients with histologically confirmed differentiated thyroid carcinoma and enrolled in the national German Society for Pediatric Oncology and Hematology-malignant endocrine tumor registry between January 1997 and February 2025. Synchronous tumors were defined as two distinct malignancies diagnosed within 3 months prior to disease-specific therapy. Clinical, pathological, and genetic findings were analyzed descriptively. Five patients (0.9%) were diagnosed with synchronous differentiated thyroid carcinoma and a second primary malignancy. All thyroid tumors were papillary thyroid carcinomas, identified in the context of Hodgkin lymphoma (n=2), pheochromocytoma, synovial sarcoma, and Ewing sarcoma. In four cases, the thyroid tumor was detected during staging or evaluation for the primary malignancy. In one patient, the papillary thyroid carcinoma was diagnosed and treated prior to the identification of Hodgkin lymphoma. One patient harbored a pathogenic succinate dehydrogenase [ubiquinone] iron-sulfur subunit variant, and two patients had coexisting Hashimoto thyroiditis. All patients achieved complete remission. Synchronous presentation of differentiated thyroid carcinoma and other malignancies in pediatric patients, while rare, poses significant diagnostic and therapeutic challenges. These cases warrant multidisciplinary evaluation and may reflect underlying cancer predisposition, immune dysregulation, or previously unrecognized risk factors. Differentiated thyroid carcinoma is the most common endocrine malignancy in children and typically presents as an isolated tumor. The synchronous occurrence of differentiated thyroid carcinoma with a second, non-thyroid primary malignancy is exceptionally rare and poorly characterized in pediatric patients.We reviewed 571 pediatric patients with histologically confirmed differentiated thyroid carcinoma and enrolled in the national German Society for Pediatric Oncology and Hematology–malignant endocrine tumor registry between January 1997 and February 2025. Synchronous tumors were defined as two distinct malignancies diagnosed within 3 months prior to disease-specific therapy. Clinical, pathological, and genetic findings were analyzed descriptively.Five patients (0.9%) were diagnosed with synchronous differentiated thyroid carcinoma and a second primary malignancy. All thyroid tumors were papillary thyroid carcinomas, identified in the context of Hodgkin lymphoma (n=2), pheochromocytoma, synovial sarcoma, and Ewing sarcoma. In four cases, the thyroid tumor was detected during staging or evaluation for the primary malignancy. In one patient, the papillary thyroid carcinoma was diagnosed and treated prior to the identification of Hodgkin lymphoma. One patient harbored a pathogenic succinate dehydrogenase [ubiquinone] iron–sulfur subunit variant, and two patients had coexisting Hashimoto thyroiditis. All patients achieved complete remission.Synchronous presentation of differentiated thyroid carcinoma and other malignancies in pediatric patients, while rare, poses significant diagnostic and therapeutic challenges. These cases warrant multidisciplinary evaluation and may reflect underlying cancer predisposition, immune dysregulation, or previously unrecognized risk factors. Das differenzierte Schilddrüsenkarzinom (DTC) ist das häufigste endokrine Malignom bei Kindern und tritt typischerweise als isolierter Tumor auf. Das synchrone Auftreten eines DTC mit einem zweiten, nicht-schilddrüsenbezogenen primären Malignom ist bei pädiatrischen Patienten äußerst selten und nur unzureichend charakterisiert.Wir untersuchten 571 pädiatrische Patienten mit histologisch bestätigtem DTC, die in das nationale (GPOH-)MET Register zwischen Januar 1997 und Februar 2025 aufgenommen wurden. Synchrone Tumoren wurden als zwei unterschiedliche Malignome definiert, die innerhalb von drei Monaten im Rahmen der krankheitsspezifischen Therapie diagnostiziert wurden. Die klinischen, pathologischen und genetischen Befunde wurden deskriptiv analysiert.Bei fünf Patienten (0,9%) wurde ein synchrones DTC und ein zweites primäres Malignom diagnostiziert. Alle Schilddrüsentumoren waren papilläre Schilddrüsenkarzinome (PTCs), die im Zusammenhang mit einem Hodgkin-Lymphom (n=2), einem Phäochromozytom, einem Synovialsarkom und einem Ewing-Sarkom identifiziert wurden. In vier Fällen wurde der Schilddrüsentumor während des Stagings entdeckt. Bei einem Patienten wurde das PTC vor der Identifizierung des Hodgkin-Lymphoms diagnostiziert. Ein Patient wies eine pathogene SDHB-Variante auf, und zwei Patienten hatten eine gleichzeitig bestehende Hashimoto-Thyreoiditis.Das gleichzeitige Auftreten von DTC und anderen bösartigen Tumoren bei pädiatrischen Patienten ist zwar selten, stellt jedoch eine diagnostische und therapeutische Herausforderung dar. Diese Fälle erfordern eine multidisziplinäre Beurteilung und können auf eine zugrundeliegende Krebsprädisposition, eine Immundysregulation oder bisher unerkannte Risikofaktoren hinweisen.
Only one-third of children with cancer survive in developing countries, including African countries. Timely diagnosis, early treatment initiation, and access to cancer treatment are integral components of pediatric oncology care to improve the outcomes of children with cancer. The primary aim of this study was to assess the time to diagnosis (TD), and patterns of delay among newly diagnosed pediatric solid cancer patients and to investigate associated factors affecting time to diagnosis in a tertiary referral hospital in Ethiopia. This prospective study was conducted in the Pediatric Hematology and Oncology (PHO) unit, Department of Pediatrics and Child Health, Tikur Anbessa Specialized Hospital, Addis Ababa University, from May 2023 to May 2024. All children < 15 years old with newly diagnosed solid cancers were included in the study. The prediagnostic and pretreatment time intervals were classified into Time to Presentation (TP), Time to Referral (TR), Time to Registration (Tr), Time to Definitive Diagnosis (TDD), Time to Diagnosis (TD), and Time to Treatment (TT) from the onset of symptoms and signs to the confirmed diagnosis at the oncology treatment center, and the initiation of treatment. The parental delay, referral delay, physician delay, health care system delay, treatment delay, total delay, and associated factors were also investigated. A total of 250 children with newly diagnosed solid cancers (excluding hematolymphoid cancers) were prospectively studied with a male-to-female ratio of 1.3:1, and 49.2% of children were between 1 and 5 years old. Central nervous tumors, and renal tumors were the most common solid cancers accounting for 24%, and 17.2% respectively. The median times for TP, TR, and TD were 30, 30, and 99 days respectively. The median parental, physician, healthcare system, and total time interval were 38 (IQR 12-152), 40 (IQR 15-92), 46 (IQR 21-100), and 112 (IQR 53-277) days, respectively. The shortest total interval delay was seen in patients with germ cell tumors, neuroblastoma, and wilms tumor. About 63.6% of children with cancer had a referral delay to the oncology center of more than two weeks, and the main factors were misdiagnosis of cancer and patient management for non-oncologic diseases. The associated factors affecting the time of diagnosis (TD) were parental education status (p = 0.032), the presence of community-based health insurance (p = 0.022), types of solid cancers (p = 0.04), and sites of the tumor (p = 0.035). Educating the caregivers, training about the symptoms and signs of childhood cancer presentations to the healthcare professionals, and designing policies and strategies for early diagnosis, referral and treatment of childhood cancer is crucial for better outcomes.
Eligibility criteria safeguard trial integrity and safety, yet restrictive requirements frequently limit patient access and generalizability. While initiatives exist to simplify criteria in adult populations, evidence supporting their use and justification within pediatric oncology remains undefined. Sixty-four protocols from 48 ITCC phase I-II trials (2011-2020) were evaluated. Protocol, literature analysis, and regulatory standards review was performed. Eligibility criteria were quantified and categorized by frequency: High (appeared in >66% of protocols), average (33%-66%), and low (<33%). For each high-frequency and relevant criteria identified in the literature review, the scientific justification provided within the trial protocol was assessed. Analysis revealed a median of 28 criteria per protocol (range 12-49), with a significant increase between 2011-2016 and 2017-2020 (p = 0.05). Substantial heterogeneity was observed in organ function thresholds and washout periods, irrespective of investigational agent characteristics. Repetition was prevalent; 69% of trials repeated similar criteria in both inclusion and exclusion sections. Notably, a median of only 7% (range 0%-62%) of high-frequency and relevant criteria possessed scientific justification within the protocol, with several exclusion categories lacking justification entirely. Pediatric early-phase trial eligibility criteria are increasingly complex, heterogeneous and predominantly lacking justification. We recommend implementing evidence-based, medically relevant requirements to optimize patient accrual and representation. Harmonizing these standards is essential to maintain safety while ensuring broader access to innovative therapies in pediatric drug development.
To explore current practices and barriers in pediatric neuro-oncology care coordination, and to identify opportunities to optimize care pathways. Timely coordination between pediatric neurosurgery and oncology is critical for optimal outcomes in children with central nervous system (CNS) tumors. However, in many centers, pediatric oncologists are not involved until after surgery, which contributes to treatment delays and repeated procedures. A cross-sectional survey was conducted among neurosurgeons and pediatric oncologists in Saudi Arabia. The questionnaire addressed the timing of oncological involvement, neuroimaging practices, cerebrospinal fluid (CSF) cytology collection, and opinions on care coordination solutions. A total of 62 responses were obtained. Only 29% of the participants reported presurgical oncology involvement in their typical practice, whereas 58% indicated that involvement occurred only after the final pathology results were obtained. Neuroimaging protocols varied: only 56.5% always performed dedicated CNS tumor magnetic resonance imaging (MRI) protocols before surgery, and spinal MRI was often delayed. CSF cytology practices were inconsistent, and major barriers included the lack of multidisciplinary tumor boards and the belief that oncology input before pathology is unnecessary. Over 88% of the respondents supported the use of presurgical tumor boards as a solution. There is substantial heterogeneity in pediatric neuro-oncology coordination practices. Efforts to promote early oncology consultations, standardized imaging protocols, and integrated care discussions may bridge critical gaps in care delivery.
Background: Choline is an essential nutrient crucial for liver function. It is required for bile and lipoprotein secretion and the synthesis of both phosphatidylcholine (PC) to ensure tissue homeostasis and betaine as a methyl donor. Choline deficiency has been implicated in the pathogenesis of intestinal failure-associated liver disease (IFALD), with the strongest evidence for its contribution to hepatic steatosis in patients with short bowel syndrome (SBS). Contributing factors are (1) an impaired recycling of choline from bile PC, leading to fecal choline losses; (2) small bowel bacterial overgrowth resulting in choline degradation prior to absorption; and (3) parenteral nutrition (PN) insufficient to meet choline requirements. However, data on choline status and its metabolites in pediatric patients with SBS are scarce. Objective: To investigate plasma levels of choline and choline-related metabolites in children with SBS and evaluate differences according to PN dependency and the presence of hepatic steatosis. Methods: Retrospective analysis of data from SBS patients managed at our intestinal rehabilitation program between March 2021 and July 2025. Target parameters in plasma samples were measured using tandem mass spectrometry. Statistical analysis and group comparison of laboratory and clinical data were performed. Results: A total of 127 samples from 80 children with SBS (0.2-17.9 years) were analyzed. Plasma choline, betaine, and PC concentrations were low, with 25% of patients showing markedly reduced choline and betaine levels below 6.4 µmol/L and 16 µmol/L, respectively. TMAO concentrations, indicating bacterial choline degradation, showed extreme variability (0-30 µmol; normal < 3 µmol/L), being inversely correlated with plasma choline levels. PC subgroups containing eicosapentaenoic acid and docosahexaenoic acid were increased in patients receiving PN. However, the only difference between steatotic and non-steatotic patients was the decreased plasma concentrations of both choline and betaine. Conclusions: Patients with SBS, with and without PN, are at risk of choline and betaine deficiency, which is associated with IFALD-steatosis. Controlled trials on choline supplementation in pediatric patients with SBS are warranted.
This study aims to comprehensively evaluate the efficacy and safety of Antibiotic Lock Therapy (ALT) in pediatric patients and to better clarify its role in catheter management. This retrospective single-center study was conducted between October 2021 and October 2024. Of 53 eligible patients, 47 received ALT and constituted the primary analysis population for treatment outcomes; 6 patients underwent immediate catheter removal without ALT and were excluded from the ALT efficacy analysis. Demographic, clinical, and microbiological data from all patients were collected. A total of 70 catheter-related bloodstream infection (CRBSI) episodes were identified among 47 patients, corresponding to an incidence rate of 12.79 per 1,000 catheter-days. The most frequently isolated pathogens were coagulase-negative staphylococci (CoNS), followed by gram-positive bacilli and Klebsiella spp. Antibiotic Lock Therapy (ALT) was administered to 47 patients and was successful in 70.2% of these cases (33/47) (p = 0.038). Among patients who did not receive ALT and required catheter removal, Klebsiella spp. and methicillin-resistant CoNS (MRCoNS) were the predominant organisms associated with sepsis and infection. In patients requiring catheter removal despite receiving ALT, gram-negative organisms were the most common pathogens, followed by gram-positive bacilli. Notably, infections most frequently developed between days 11 and 45 of catheter use, indicating a critical high-risk window for catheter-related infections. Catheter-related infections remain a significant clinical challenge in pediatric hematology-oncology patients. Our findings suggest that ALT was associated with catheter retention in a considerable proportion of patients; however, given the retrospective design and potential for confounding by indication, this observation should be interpreted cautiously rather than as a definitive efficacy claim. The identification of a high-risk period between days 11 and 45 may support closer monitoring and earlier intervention. Further prospective studies with standardized selection criteria are required to validate and standardize the use of ALT in this vulnerable population.
Background: Medulloblastoma is the most common malignant pediatric central nervous system tumor and exhibits marked molecular and clinical heterogeneity. Immune evasion pathways may contribute to tumor aggressiveness and represent potential prognostic and therapeutic targets. We investigated the clinicopathological and prognostic relevance of the immune checkpoint molecules B7-H3 (CD276) and CD47 in medulloblastoma. Methods: We screened 77 patients treated between April 2015 and December 2025; in total, 32 patients with pathologically confirmed medulloblastoma and complete data were included. Tumor B7-H3 and CD47 expression was assessed using immunohistochemistry and an immunoreactivity score (IRS); patients were categorized as having negative/low (IRS < 4) or high (IRS ≥ 4) expression. We analyzed the associations with clinicopathological and molecular features. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier and log-rank tests. Prognostic factors were examined using univariate and multivariate Cox regression. Results: High B7-H3 expression was associated with shorter OS (median 46 vs. 85 months; p = 0.024) and markedly reduced DFS (median 21 vs. 102 months; p < 0.001). High CD47 expression was also associated with shorter OS (median 56 vs. 102 months; p = 0.025), whereas DFS did not significantly differ by CD47 status (p = 0.200). B7-H3 and CD47 expression levels were not correlated (Spearman's rho = 0.071; p = 0.699). In the univariate analysis, high B7-H3 expression predicted mortality (HR = 25.79; p = 0.002) and recurrence risk (HR = 136.23; p = 0.045), and high CD47 expression predicted mortality (HR = 4.82; p = 0.042). In the multivariate analysis, high B7-H3 expression remained an independent predictor of poor OS (HR = 31.01; p = 0.004), whereas radiotherapy independently reduced the recurrence risk (HR = 0.197; p = 0.024). Conclusions: B7-H3 is a strong independent adverse prognostic biomarker for OS and is associated with profoundly shorter DFS in medulloblastoma, supporting its relevance as a candidate target for immune-directed strategies.
To evaluate the current status, clinical capacity, and key barriers related to chimeric antigen receptor T-cell (CAR-T) therapy in Türkiye and to inform national policy development. From June 2023 to March 2024, the Scientific Subcommittee on Cell and Gene Therapies of the Turkish Society of Hematology conducted two nationwide online surveys and held three multidisciplinary meetings with contributions from hematologists, basic scientists, and key stakeholders. Survey findings were integrated with the meeting outputs and recent regulatory developments. Surveys indicate a marked gap between the estimated annual need (about 507 patients) and actual access to CAR-T therapy. Between 2019 and March 2024, only 23 patients in Türkiye received CAR-T therapy. Major barriers included high treatment costs, insufficient infrastructure, and a limited number of trained personnel. Expert meetings further highlighted challenges with regulatory pathways, reimbursement, and the need for standardized production and clinical protocols. Despite these limitations, participants demonstrated strong clinical readiness and consensus on the need to improve access. The implementation of CAR-T therapy in Türkiye continues to be impeded by structural and economic limitations. It is imperative to develop a strategic national roadmap that encompasses: 1) the establishment of a national academic CAR-T network, 2) the securing of sustainable funding and legal frameworks,3) the implementation of hospital-exemption pathways, 4) the development of a centralized registry, 5) the expansion of structured training programs, and 6) the enhancement of international collaborations. These measures are fundamental for the sustainable integration of this therapy into clinical practice. Bu çalışmanın amacı, Türkiye’de kimerik antijen reseptörlü T hücre (CAR-T) tedavisinin mevcut durumunu, klinik kapasitesini ve başlıca kısıtlayıcı faktörleri değerlendirmek ve ulusal politika geliştirme süreçlerine bilimsel veri sağlamaktır. Haziran 2023–Mart 2024 döneminde, Türk Hematoloji Derneği Hücre ve Gen Tedavileri Bilimsel Alt Komitesi tarafından ülke çapında iki çevrimiçi anket uygulanmış ve hematologlar, temel bilimciler ile ilgili paydaşların katılımıyla üç multidisipliner toplantı gerçekleştirilmiştir. Elde edilen anket verileri, toplantı çıktıları ve güncel düzenleyici gelişmelerle bütüncül olarak analiz edilmiştir. Anket bulguları, yıllık tahmini ihtiyaç (yaklaşık 507 hasta) ile CAR-T tedavisine erişim arasında belirgin bir uyumsuzluk olduğunu ortaya koymaktadır. 2019 ile Mart 2024 tarihleri arasında Türkiye’de yalnızca 23 hastaya CAR-T tedavisi uygulanmıştır. Başlıca kısıtlayıcı faktörler; yüksek tedavi maliyetleri, yetersiz kurumsal altyapı ve sınırlı sayıda eğitimli insan kaynağı olarak belirlenmiştir. Uzman toplantılarında ayrıca düzenleyici süreçlerdeki belirsizlikler, geri ödeme mekanizmalarındaki yetersizlikler ve standartlaştırılmış üretim ile klinik uygulama protokollerine duyulan gereksinim vurgulanmıştır. Tüm bu sınırlılıklara karşın, katılımcılar güçlü bir klinik hazırlık düzeyine sahip olduklarını ve erişimin artırılması gerekliliği konusunda yüksek düzeyde görüş birliği bulunduğunu ifade etmiştir. Türkiye’de CAR-T tedavisinin klinik uygulamaya entegrasyonu, yapısal ve ekonomik sınırlılıklar nedeniyle halen kısıtlıdır. Bu bağlamda, sürdürülebilir bir ulusal stratejik yol haritasının geliştirilmesi kritik önem taşımaktadır. Bu yol haritası kapsamında; 1) ulusal akademik CAR-T ağının oluşturulması, 2) sürdürülebilir finansman modelleri ve destekleyici yasal düzenlemelerin hayata geçirilmesi, 3) hastane muafiyeti (hospital exemption) mekanizmalarının uygulanması, 4) merkezi bir ulusal kayıt sisteminin kurulması, 5) yapılandırılmış eğitim programlarının yaygınlaştırılması ve 6) uluslararası iş birliklerinin güçlendirilmesi temel öncelikler olarak öne çıkmaktadır.
To explore how nurses comfort pediatric hematology-oncology (PHO) patients, examine nurses' confidence and educational preparation in providing comfort, and inform recommendations for enhancing new nurses' readiness. Seventeen PHO nurses in the southeastern United States were recruited through professional networks and PHO-focused organizations to complete an anonymous online survey. PHO nurses completed a survey with 12 closed and 4 open-ended questions. Open-coding content analysis was used to derive themes about how nurses comfort PHO patients. Demographic data were analyzed using descriptive statistics. A conceptual model described how nurses comfort PHO patients through dynamic individualized care using the approaches of preparation, comforting presence, listening, and distraction. More experienced nurses appeared to be more likely to identify listening as a comforting approach. Nurses who were more confident using comfort approaches appeared to be more likely to use them. Comfort care is a particular priority when caring for a PHO patient. Understanding nurses' readiness to provide comfort and how they approach this key aspect of PHO care strengthens patient care and nursing practice transitions. There are opportunities to increase education and readiness for this nursing role.
The epidemiology of acute leukemia (AL) in children in Afro-descendant (AD) populations is poorly described, and survival is often considered worse in these populations. The aim of this study is to describe the epidemiology and prognosis of childhood AL in the AD population of the French West Indies/French Guiana (FWI/FG). This is a multicenter, retrospective, descriptive cohort study of children aged 0-17 years old, resident of the FWI/FG and diagnosed with AL between January 2010 and December 2022. Patients were identified via the French National Childhood Cancer Registry and cross-referenced with lists from each reference center and local registry. The Kaplan-Meier method was used to estimate 5-year overall survival (5y-OS) and event-free survival (5y-EFS). A total of 107 patients were included, 67% B-Acute lymphoblastic leukemia (ALL), 18% AML, and 14% T-ALL. The age standardized incidence rate for childhood AL was 32.9 (21.4-46.2) per million-year for children. The 5y-OS rate for all children was 90.9% (95% CI: 84.1-98.2), and 93.1% (95% CI: 85.8-100) for B-ALL, 91.7% (95% CI: 77.3%-100%) for T-ALL and 83.1% (95% CI: 64.1%-100%) for AML. The 5y-EFS were respectively 75.8% (95% CI: 66.3-86.5), 78.3% (95% CI: 67.6-90.8) and 83.9% (95% CI: 65.7-100) for all children, B-ALL and T-ALL. Seven patients (7%) died, mostly due to disease progression (57%). This is the largest epidemiological study reported on childhood AL in an AD population and in the Caribbean/Latin America zone. Survival rates in our AD population were similar to those described in European and North American studies and much better than in the Caribbean and Latin American zone.
Our study aimed to investigate the experiences of adolescents and young adults (AYAs) with cancer from racially/ethnically diverse and/or 2SLGBTQIA + communities within the Canadian healthcare system to identify areas for improvement in their cancer care experience. The study included participants who self-identified as racially/ethnically diverse and/or 2SLGBTQIA + , diagnosed with cancer between ages 15 and 39 years, currently aged 18 years or older, and received or were receiving cancer care in Canada. Patient partners with lived experience of cancer were recruited as collaborators. Semi-structured virtual interviews were conducted using an interview guide, and transcripts were analyzed using framework analysis. Twenty-three participants (17 racially/ethnically diverse; 1 sexual/gender diverse; 5 both racially and sexually diverse) were interviewed. Positive experiences reported by participants included being able to identify with healthcare providers (HCPs), effective communication, comprehensive information sharing, and access to support services tailored for younger patients. Negative experiences were characterized by perceptions of judgmental attitudes and racialization from HCPs, the necessity of self-advocacy to obtain resources, systemic barriers to care, and psychosocial difficulties. Participants' recommendations for improving cancer care included increasing the diversity of HCPs, implementing equity, diversity, and inclusion training, and enhancing both communication and information dissemination practices. The experiences of diverse AYAs revealed both facilitators and barriers to equitable cancer care. Findings emphasize the need for workforce diversity and equity-informed practices to advance culturally responsive oncology care. Précis: This study examined the cancer care experiences of racially/ethnically diverse and/or 2SLGBTQIA + adolescents and young adults in Canada, revealing both supportive interactions and significant barriers such as discrimination and systemic inequities. Participants recommended increasing provider diversity, equity-focused training, and improved communication to create more inclusive and responsive cancer care.
M-HLH is a type of HLH that most often occurs in children in the course of hematological malignancies. The diagnosis is based on meeting the criteria of the HLH-2004 Protocol. The disease has a rapid course, and the lack of proper diagnosis and treatment threatens the patient's life. The paper presents the thorough clinical characteristics, course of treatment, and treatment results in 23 patients treated in pediatric hemato-oncology centers in Poland and reported to Polish HLH registry. HLH diagnostic criteria, CNS involvement, coexisting viral infections, genetic test results, treatment modalities, therapeutic responses, relapse incidence, and final outcomes were analyzed. Clinical and laboratory factors were subjected to statistical analysis. Overall survival was estimated using the Kaplan-Meier method for the entire cohort and separately for subgroups defined by type of malignancy and treatment strategy. Separate univariable Cox proportional hazards models were used to explore the association between selected clinical factors and survival. The median age at diagnosis was 11.7 years, in 8 patients HLH symptoms preceded the cancer diagnosis. Acute leukemia was the factor causing M-HLH in 12 patients, in the remaining patients it was lymphoma. The treatment included tumor-directed therapy with or without HLH-directed therapy. The probability of survival in the study group was 0.539 (95% CI 0.364-0.798). Remission of HLH was statistically significant (p-value = 0.0007) and reduced the risk of death by 90% (HR=0.10). Quick and precise diagnosis and implementation of appropriate treatment bringing the patient into HLH remission is extremely important for survival.
Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of B-cell precursor ALL (B-ALL), but its global availability is limited. This study assessed current access and barriers to CAR-T CD19 therapy for children across Europe. A country questionnaire developed by the European Group for Blood and Marrow Transplantation Pediatric Diseases Working Party, St Jude Children's Research Hospital, and IBFM assessed current access to advanced therapies for B-ALL in Europe using Qualtrics software. Data from 36 WHO-defined European countries (27 high-income, nine upper-middle-income) observed a median of five pediatric hematology-oncology (PHO) centers per country (0.56 PHO centers/1 million inhabitants, range, 0.05-1.83). Hematopoietic stem-cell transplantation (HSCT) facilities were available in 89% of countries (32/36). CAR-T CD19 therapy was available in 72% of countries; however, 25/36 (69%) countries lacked clinical trials or international collaborations for pediatric CAR-T CD19 therapy. Most countries accepted foreign patients, but referrals remained limited, with 1-2 foreign patients treated annually per country. Eighteen countries expressed interest in a referral network, but only six had established mechanisms for domestic or international referrals. Substantial disparities exist in access to advanced therapies for pediatric B-ALL across Europe. Although CAR-T CD19 therapy is available in most countries, gaps in clinical trials, collaborations, and referral systems limit equitable access. Efforts to improve infrastructure and establish referral networks are essential to enhance care for patients with pediatric B-ALL.
Accurate detection of macroscopic residual disease after neuroblastoma resection is essential for postoperative treatment decisions, including radiotherapy. Standard imaging follow-up is often performed at a time point when postoperative and therapy-related changes may hamper reliable differentiation between residual disease and reactive findings. To assess inter-reader agreement and the diagnostic accuracy of early postoperative magnetic resonance imaging (MRI) for detecting residual disease after neuroblastoma surgery. This retrospective single-center study included patients with histologically confirmed neuroblastic tumors who underwent surgical resection at a reference center and received standardized early postoperative MRI with adequate preoperative imaging. Two independent pediatric radiologists, blinded to all clinical data, assessed all examinations. A hierarchical multimodal reference standard was established based on surgical reports including expert consensus between a senior pediatric radiologist and a pediatric surgeon, and follow-up imaging (median follow-up 33 months). Thirty-nine patients (median age 46 months), predominantly with International Neuroblastoma Staging System (INSS) stage 4 neuroblastoma, were included; all patients had at least one image-defined risk factor. MRI was performed at a mean of 8±5 days after surgery. Residual disease was identified in 14 patients and confirmed by the reference standard. Five residual diseases were expected by the surgeons (median volume 8 ml), whereas nine were unexpected and small (median volume 1 ml). Diagnostic accuracy were 95% and 90% for the two readers, respectively, with substantial inter-reader agreement (Cohen's κ=0.76). Early postoperative MRI findings led to clinically relevant management adaptations in selected cases. Early postoperative MRI demonstrates high diagnostic accuracy and substantial inter-reader agreement in detecting macroscopic residual disease, providing a robust baseline for further assessment.
Hematopoietic stem cell transplantation (HCT) offers curative potential for children with high-risk hematologic malignancies. However, this treatment carries significant risks, particularly acute graft-versus-host disease (aGvHD), which affects 30%-60% of pediatric recipients and causes 15%-20% of post-transplant deaths. The gut microbiome has emerged as a critical factor in aGvHD development, yet pediatric microbiome dynamics differ substantially from adult patterns. This review seeks to evaluate the current state of knowledge of how the gut microbiome impacts aGvHD pathogenesis and the methods of microbiome modulation that may lead to aGvHD prevention and treatment. Children's microbiomes undergo more rapid compositional shifts and contain distinct bacterial compositions enriched in taxa like Bifidobacterium and Lactobacillus. During transplant, conditioning regimens and antibiotics cause dramatic microbiome disruption in children. This eliminates beneficial bacteria that normally maintain intestinal barrier integrity and produce immunomodulatory metabolites. Consequently, this disruption triggers inflammatory cascades through bacterial translocation, impaired immune education, and altered metabolite production. Unlike adults, where low diversity consistently predicts poor outcomes, pediatric studies show inconsistent diversity-outcome relationships, with only pre-transplant microbiome patterns reliably predicting aGvHD risk. Several promising interventions have emerged from this research. These include enteral nutrition to preserve beneficial bacteria, targeted antibiotic strategies, and fecal microbiota transplantation. Fecal microbiota transplantation has shown remarkable response rates in pediatric steroid-resistant aGvHD cases. Nevertheless, significant knowledge gaps remain regarding pediatric-specific mechanisms, optimal biomarkers, and age-appropriate therapeutic approaches for microbiome-directed aGvHD prevention.
Magnetic resonance elastography (MRE) is a noninvasive technique for assessing viscoelastic properties of soft biological tissues in vivo, with potential relevance for tumor evaluation. This exploratory study aimed to assess the feasibility of multifrequency MRE in pediatric extracranial solid tumors and to investigate potential associations between viscoelastic parameters and different rare pediatric tumor entities. Ten pediatric patients (mean age, 5.7 ± 4.8 years; four female) with extracranial solid tumors underwent multifrequency MRE in this prospective study. Shear waves at 30-70 Hz were subsequently generated and measured with a phase-sensitive single-shot spin-echo planar imaging sequence. The obtained shear wave fields were processed by wavenumber (k-)based multi-frequency inversion to reconstruct tumor stiffness and fluidity. Viscoelastic properties within the tumors were quantified and correlated with the apparent diffusion coefficient (ADC). Differences in stiffness and fluidity were assessed across histopathologically confirmed tumor entities, stratified into malignancy-based groups. MRE was successfully performed in all patients within less than five minutes. Viscoelastic properties varied among tumor entities, with a tendency toward higher stiffness, fluidity, and spatial heterogeneity in tumors assigned to higher malignancy groups (all p < 0.05). Stiffness (p > 0.05) and fluidity (p < 0.05) showed inverse associations with tumor ADC values. Multifrequency MRE can be integrated into pediatric MRI examinations and provides quantitative information on tumor viscoelastic properties. Differences in stiffness and fluidity were observed across pediatric extracranial solid tumors with higher values in tumors assigned to higher risk groups. These preliminary findings suggest that MRE-derived parameters may provide complementary information for tumor characterization.
Replication-repair-deficiency is associated with increased risk of developing malignant gliomas. The aim of this study was to investigate primary mismatch repair deficient gliomas (PMMRDGs), a group of IDH-wildtype and H3-wildtype gliomas that is enriched among patients with CMMRD and Lynch syndrome. We investigated how PMMRDGs differ from other gliomas with respect to DNA methylation profile, genomic alterations, histopathology, and clinical outcomes. PMMRDGs occur in pediatric, adolescents and the elderly, falling in two related methylation clusters and are characterized by a high frequency of replication repair deficiency. Histology showed multinucleated giant cells, and immunohistochemistry demonstrated loss of MMR protein expression. Survival analysis revealed long-term survival in patients with high mutational burden (>50 mut/Mb) and an intact chromosome 9p region, which was validated in an independent reference cohort. Overall, our findings indicate that PMMRDGs represent a distinct type of IDH-wildtype gliomas with potential for long-term survival likely driven by immune activation. In this study we investigate a group of brain tumors linked to inherited problems in DNA repair. These tumors can occur in children, adolescents, and older adults. We analyzed their molecular features, tissue appearance, and patient outcomes and found that these tumors form a distinct group with many genetic changes and characteristic giant tumor cells. Importantly, some patients lived much longer, especially when their tumors had a very high number of mutations and retained a specific chromosome region. These findings show that this tumor type is biologically unique and may benefit from immune system activity, offering hope for improved treatment strategies.
Hodgkin lymphoma (HL) comprises 6% of pediatric cancers, showing bimodal incidence in adolescence/young-adult and over 50 years. Characterized by Reed-Sternberg cells, HL is classified as classic/nodular lymphocytic predominant by WHO. Hypereosinophilia (>1,500/µL eosinophils) occurs in 15% of HL cases. A 17-year-old female presented with weight loss, night sweats, and malaise. Examination showed enlarged lymph nodes, splenomegaly, and palmoplantar erythema. Bloodwork revealed eosinophilia, hypoalbuminemia, and elevated lactate dehydrogenase levels. Bone marrow confirmed eosinophilic predominance. Lymph node biopsy diagnosed nodular sclerosis classical Hodgkin lymphoma (NS-cHL). PET-CT scan identified cervical, mediastinal, abdominal and spleen tumoral activity, classified as classical Hodgkin lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma according to WHO criteria. OEPA/COPDAC treatment initiated, follow-up PET-CT showed incomplete metabolic response. She subsequently underwent radiotherapy, achieving complete metabolic response after treatment. This rare case illustrates profound hypereosinophilia concomitant with HL. Despite an extensive literature search, similar presentations are rarely reported in the literature. This case highlights an uncommon association between classical Hodgkin lymphoma and unusually high levels of hypereosinophilia, supported by the clinical course and the marked decline in eosinophil counts after lymphoma-directed therapy.
T-cell prolymphocytic leukemia (T-PLL) is a rare and highly aggressive mature T-cell malignancy that predominantly affects older adults. Its occurrence in childhood is exceptionally uncommon and may mimic other neoplasms, such as lymphoma or thymoma, particularly when associated with mediastinal masses or generalized lymphadenopathy. A 13-year-old Turkish girl presented with severe respiratory distress. Thoracic imaging demonstrated a large anterior mediastinal mass. In the prevascular mediastinal compartment, the most common tumors include thymoma, germ cell neoplasms, and lymphoma. The initial needle biopsy was of limited diagnostic value due to crush artifacts and demonstrated a T-cell-predominant infiltrate with focal keratin positivity, initially suggestive of a thymic neoplasm. Based on this preliminary interpretation, empiric chemotherapy for presumed advanced thymoma was initiated. However, detailed systemic radiological assessment revealed that the mass was not confined to the mediastinum but also accompanied by widespread lymphadenopathy. Subsequent systemic radiological evaluation revealed widespread lymphadenopathy beyond the mediastinum, prompting an incisional lymph node biopsy. Immunohistochemical analysis revealed a neoplasm lacking an epithelial component (negative for P63, pancytokeratin, and cytokeratin) and composed entirely of lymphoid cells. The tumor cells showed diffuse positivity for CD45, CD3, CD5, CD8, and BCL-2, with a high Ki-67 proliferation index, and were negative for immaturity markers (CD34, TdT, CD33). Taken together, these findings supported a mature T-cell neoplasm most consistent with T-PLL, although the absence of molecular confirmation limited definitive diagnostic certainty. Bone marrow evaluation was non-diagnostic. This case illustrates the diagnostic challenges of pediatric T-PLL and demonstrates that a multidisciplinary correlation of clinical, histological, immunophenotypic, and molecular features-together with repeated biopsy and comprehensive immunophenotyping-can be decisive for timely and accurate diagnosis.