Purpose Transfusion-Related Iron Overload (TRIO) is a late effect of therapy impacting survivors of childhood cancer and hematopoietic stem cell transplantation (HSCT) who receive frequent packed red blood cell (pRBC) transfusions. Surprisingly, there are no accepted guidelines to assist providers in identifying and treating at-risk patients following therapy. Our primary aim was to create an evidence-based clinical practice guideline (CPG) for the surveillance of TRIO and measure its impact on care at Helen DeVos Children’s Hospital.    Methods We compared the rates at which screening laboratory and confirmatory imaging studies were obtained two years before and six months after CPG implementation.     Results  Labs more commonly obtained post-implementation included iron studies such as TIBC (p = .0077), TSAT (p= .0133), and serum iron (p = .0208) and hepatic injury markers such as AST/ALT (p= .0278), ALP (p = .0073), and total bilirubin (p = .0026). Liver MRI/FerriScan (p = .0343) and echocardiogram were also more commonly obtained post-implementation. We additionally found a positive correlation between HSCT and TRIO (p= .0010) and number of pRBC transfusions and TRIO (p= .0025). Gender, age, and weight did not impact the rates of TRIO in either cohort. There was no association between diagnosis category (solid tumor, leukemia/lymphoma, or non-malignant disease) and TRIO. Among HSCT patients, we did not find any relationship between TRIO and donor source, ABO compatibility status, or the type of conditioning therapy.    Conclusion  The implementation of a TRIO CPG can significantly influence post-therapy care. Although our cohort size was limited, we did not observe an association between gender, age, weight, diagnosis category, donor source, ABO compatibility status or HSCT conditioning modality and a diagnosis of TRIO.

Central venous access is essential for delivering chemotherapy and supportive care in children with cancer. Yet the practical decisions surrounding device selection, placement, maintenance, and salvage vary widely among institutions. In our center, we use a systematic, multidisciplinary workflow to anticipate the treatment trajectory, prioritize venous preservation, prevent complications, and support structured salvage strategies when device dysfunction or infection occurs. This “How I Approach” article outlines a pragmatic, experience-based model drawn from daily practice in a high-volume pediatric oncology setting. The focus is on applying established concepts to real-world clinical decision-making to maintain continuity of therapy and minimize morbidity.

Germline MRAS variant in an infant with bilateral adrenal neuroblastomaGorkem Oztosun, MD1; Eric Hawley, MD, PhD2; Sue L. Jaspersen, PhD, MGC, CGC3; Amy E. Armstrong, MD21: Division of Medical Oncology, Washington University in St. Louis, MO, USA2: Division of Pediatric Hematology/Oncology, Washington University in St. Louis, MO, USA3: Division of Genetic Counseling, Washington University in St. Louis, MO, USACorresponding author:Amy E. Armstrongarmstrongae@wustl.eduChildren’s Hospital, 1 Children’s PlaceSt. Louis, MO 63110314-454-6018Word count - Main text: 850Number of figures: 1Running title: germline MRAS mutation in metastatic bilateral adrenal neuroblastomaKeywords: bilateral adrenal neuroblastoma, germline MRAS, intermediate-risk neuroblastomaAbbreviation Key

Background: Equitable access to essential pediatric oncology medicines is critical for improving childhood cancer outcomes in Latin America. However, persistent disparities in availability, affordability, and quality of these medicines threaten treatment continuity and survivalThis study aimed to assess the regional landscape of access, availability, and quality of essential pediatric oncology medicines from the perspective of frontline healthcare professionals, and to identify structural barriers and opportunities for system-level improvement. Methods: A cross-sectional survey was conducted among 148 health professionals involved in the care of children and adolescents with cancer across 137 institutions in 19 Latin American countries. Respondents included national focal points for childhood cancer, responsible for supporting the implementation of the WHO CureAll framework at country level, and country delegates from the Latin American Society of Pediatric Oncology (SLAOP), ensuring participation of professionals with recognized leadership and technical expertise. A structured online questionnaire collected data on the availability, access, financing, and quality of essential pediatric oncology medicines, as well as procurement mechanisms and civil society involvement. Key outcome measures were stratified by country income level, geographic subregion, and institution type. Results: While 70% of respondents reported government-financed medicines, barriers such as administrative delays, coverage denial, and out-of-pocket payments remained widespread, especially in Central America and Mexico. Professionals in low- and middle-income countries were 2.9 times more likely to report medicine unavailability (p=0.0008) and 3.5 times more likely to request family purchases (p=0.002). Quality concerns, particularly with asparaginase, were reported by half of respondents. Civil society organizations played a pivotal role in bridging supply gaps and advocating for access, with notable engagement in countries with weaker health coverage. Conclusions: The study highlights structural and geographic inequities in pediatric oncology medicine access and quality across Latin America. Strengthening procurement systems, regulatory oversight, and civil society partnerships is essential. Regional initiatives like GPACCM and CureAll, which promote centralized purchasing and health system strengthening, are critical to ensuring equitable and sustainable access to safe and effective childhood cancer treatment.

BACKGROUND: Patients receiving allogenic hematopoietic stem cell transplant (HSCT) may experience intestinal graft versus host disease (GVHD). Intestinal GVHD is typically managed with medical therapy but surgery and angioembolization may be warranted in selected patients with complicated intestinal GVHD. METHODS: The following complications that warrant surgical consultation were identified: severe bleeding, bowel stricture or obstruction, intestinal pneumatosis and intestinal perforation. Patients diagnosed with complicated intestinal GVHD between 2010 and 2024 were retrospectively retrieved. Need for surgery and interventional radiology, mortality related to GVHD and chronic intestinal failure (CIF), defined as need for total parenteral nutrition (TPN) for more than six months or until exitus, were described. RESULTS: Eighteen patients had complicated intestinal GVHD. Fourteen (78%) had severe bleeding, with a GVHD-related mortality rate of 64% and CIF prevalence of 86%: one had angioembolization of one distal branch of superior mesenteric artery for refractory bleeding, and finally died for hepatic GVHD. Eight patients (39%) had bowel stricture, with a GVHD-related mortality rate of 50% and CIF prevalence of 75%. Four patients underwent laparotomy and bowel resection for critical stricture causing obstruction, in one case at the site of previous biopsy; two (50%) died as a consequence of GVHD, and both survivors had multiple laparotomies and eventually developed CIF. Three patients (17%) had pneumatosis; none evolved to intestinal perforation and all were all successfully treated conservatively with careful monitoring, TPN and immunosuppression. One of them (33%) eventually died for hepatic GVHD and pulmonary aspergillosis. In the whole cohort, GVHD-related mortality rate was 61% and prevalence of CIF was 78%. CONCLUSION In patients affected by complicated intestinal GVHD, uncontrolled bleeding and critical stricture causing bowel obstruction are indication for angioembolization and surgery, while pneumatosis can be treated conservatively. Given the severity of complicated intestinal GVHD, a high risk of mortality and CIF should be anticipated.

Background: Chemotherapy induced thrombocytopenia (CIT) is a complication of myelosuppressive chemotherapy that often results in delay or dose reduction of subsequent cycles. There are currently no FDA-approved agents for the treatment of CIT. Management consists of platelet transfusions, dose reductions, and delays in subsequent chemotherapy cycles, which can lead to a decrease in progression-free survival as well as overall survival in this patient population. Romiplostim is a thrombopoietin receptor agonist (TPO-RA) that binds to and activates the TPO receptor on megakaryocyte precursors, increasing platelet production. Literature to support the routine use of romiplostim and its application in the setting of CIT in pediatric patients is limited. Objective: To evaluate the safety profile and efficacy of romiplostim in achieving and maintaining platelets ≥ 75,000/mL to allow resumption of chemotherapy without recurrence of CIT in pediatric patients with solid tumors. Methods: This single-center retrospective chart review was conducted at a tertiary pediatric hospital. Patients ≤ 22 years of age were included if they received romiplostim for CIT from July 1 st, 2020, to December 31 st, 2023. The primary outcome of this study was to determine the number of patients who were responsive to romiplostim. Results: A total of 18 patients were included in the analysis. Twenty-eight percent had a diagnosis of rhabdomyosarcoma, 70% of patients had metastatic disease, and 56% had relapsed disease. A total of 12 patients (70%) were responsive to romiplostim, achieving a platelet count ≥ 75,000/μL within 3 weeks. There was an average of 2 dose reductions prior to romiplostim initiation versus 1 dose reduction during treatment with romiplostim (p=0.46) and 3 delays prior to versus 1 delay during treatment with romiplostim (p=0.0008). The average time to platelet count ≥ 75,000/μL was 30 days prior to romiplostim versus 15 days during romiplostim. Conclusion: Romiplostim may decrease the number of chemotherapy dose reductions and delays in pediatric patients with CIT, but further prospective studies are necessary to determine its place in therapy.

Background: Inaccurate or imprecise diagnosis is a major contributor to treatment failure for children with cancer in low- and middle-income countries (LMICs). Sequencing-based diagnostic testing presents an opportunity to overcome diagnostic deficiencies. It is important to identify facilitators and barriers which are common to the implementation of sequencing-based diagnostics in LMICs. Procedure: Pediatric oncology research collaborators at six hospitals in LMICs were invited to participate in the study. Snowball sampling identified additional participants. Thirty-nine virtual, semi-structured interviews were conducted using interview guides informed by the Consolidated Framework for Implementation Research (CFIR) with suggested adaptations for LMICs. Rapid qualitative analysis was conducted to identify facilitators and barriers to the implementation of diagnostic sequencing for pediatric cancers. Barriers were then matched with Expert Recommendation for Implementation Change (ERIC) strategies. Results: Implementation facilitators and barriers were organized by CFIR construct. Predominant facilitators were relative advantage, culture, collective efficacy, self-efficacy, patient needs and resources, leadership engagement, knowledge and beliefs, tension for change, monitoring services for action, and implementation climate. Key barriers to implementation were cost, available resources, resource continuity, engaging participants, and resource source. Conclusions: Participants communicated that the lack of diagnostic classification for pediatric cancer in LMICs is a common key limitation to current cancer care. They described considerable motivating strengths to leverage towards this goal of developing sequencing-based diagnostic testing capacity. Resource availability, continuity, and sustainment are current barriers that must be addressed. Our data highlights the urgent need for creative global implementation partnerships as many centers in LMICs are poised to advance novel diagnostic solutions.

The communication needs of children and adolescents (C&A) with cancer are not being met. Understanding C&A communication experiences and preferences from their perspective is critical to patient-centered care and health outcomes. Our objective was to systematically review and synthesize qualitative data to describe C&A <18 years of age self-reported preferences for cancer communication specific to information exchange. We conducted a search in PubMed, PsycINFO, CINAHL, and SCOPUS databases and applied Joanna Briggs Institute qualitative review methods. Studies with participants < 18 years of age with childhood cancer were included in this synthesis. 3213 articles were identified with 55 articles included. 266 findings related to preferences for exchanging information were extracted from 43 studies. The findings were aggregated into six synthesized findings: 1) How I receive information, 2) When I want information, 3) How my healthcare team shares information with me, 4) How my parents share information with me, 5) How I get information, and 6) When I do not want information. This meta-synthesis highlights C&A with cancer have individual preferences for information exchange related to their treatment and can voice their preferences. Evidence-based practice recommendations were identified to meet their communication needs and preferences.

Sickle cell disease (SCD) is an inherited hemolytic hemoglobinopathy characterized by a wide range of complications, including chronic hemolysis, painful Vaso-occlusive crises, and progressive organ damage. At present, one of the main therapeutic options prescribed for patients with SCD is hydroxyurea capsules, often in combination with various analgesics. However, this therapeutic approach may fail to provide adequate relief during active disease episodes, particularly when severe pain crises occur. Drug repurposing has emerged as a promising strategy in situations where de novo drug development is limited or not feasible, thereby addressing existing therapeutic gaps. Compared with traditional drug development procedures, this strategy offers advantages such as reduced costs and accelerated timelines for drug discovery. Imatinib (Gleevec), which is primarily indicated as part of standard chemotherapy for patients with chronic myeloid leukemia (CML), has been considered for repurposing in SCD. Based on its known mechanisms of action, this narrative review provides a theoretical assessment of the potential applications of imatinib in SCD. Examination of the molecular pathways shared between imatinib’s targets and the pathogenesis of SCD has yielded controversial findings: some studies suggest imatinib may reduce hemolysis and alleviate pain crises, while others have not supported such benefits. Direct investigations of imatinib in the context of SCD are limited, yet available evidence has reported potentially valuable outcomes, including decreased hospitalization rates, shorter hospital durations, and reduced organ damage. Current evidence remains insufficient for definitive conclusions, underscoring the need for well-designed clinical and translational studies to clarify the feasibility of incorporating imatinib into SCD management.

Childhood cancer survivors (CCS) face elevated risks for long-term health complications, making continued follow-up care essential. Yet many remain disengaged from survivorship services. This randomized controlled pilot study tested a brief, phone-based narrative intervention aimed at increasing health care self-efficacy (HCSE), posttraumatic growth (PTG), and intent to seek care among adolescent and young adult CCS not currently in follow-up. Thirty-three participants were randomized to either the intervention or a control group. Intervention participants completed a single one-hour phone call in which they reflected on their cancer experience, identified strengths and growth, and considered how these could support re-engagement with care. All participants received a survivorship brochure; intervention participants also received a personalized summary. The intervention was feasible and well-received, with high participation and full survey completion. Compared to controls, intervention participants showed significant increases in HCSE and intent to seek follow-up care (p < .05). PTG increased in both groups with no between-group differences. No differences were observed in appointment-making behavior at four weeks. A single narrative-based session may be sufficient to boost motivation and self-efficacy, but additional strategies may be needed to translate these gains into action. This low-cost, scalable approach merits further exploration in larger, more diverse samples.

This study investigated the association between genetic variants and the occurrence of oral mucositis (OM) in pediatric patients with acute lymphoblastic leukemia (ALL) and lymphoma undergoing chemotherapy (CT). A retrospective observational longitudinal study was conducted, with daily assessment of OM using the World Health Organization scale and blood samples collected for DNA extraction. Genetic variants were analyzed through next-generation sequencing, using a gene panel focused on 67 coding regions within 20 genes. Sixty-four pediatric patients were evaluated during 392 cycles of CT, with the most commonly used protocols being DOXO (34.2%), MTX (27.8%), and CTX (17.3%). Approximately 65.8% of patients developed some degree of mucositis, with 34.7% showing ulcerative OM (Grades 2 or 3) and 9.2% presenting severe OM (Grade 3). Associations between genetic variants and OM were identified in MTX cycles (ABCC2, ABCC4, and GSTM1), CTX cycles (ABCC6, HSP90AA1, and ABCC1), and DOXO cycles (ABCC1, CYP2A7, and MTHFR). This study suggests potential future treatment strategies with the possibility of increasing efficacy, reducing toxicity, and improving survival rates in pediatric oncology patients.

Introduction: Neuroblastoma (NB) with central nervous system (CNS) metastases is rare at diagnosis but occurs more often during relapse/progression. Patients with CNS metastases face a dismal prognosis, with no standardized curative treatment available. Novel therapeutic approaches, such as intraventricular radio-immunotherapy with 131I-Omburtamab (Omb), have been developed. In this study, we report a retrospective, single tertiary center analysis of a 23-year cohort of NB patients with CNS metastases, highlighting current treatment strategies. Patients and Methods: Retrospective data analysis of all NB patients with CNS metastases treated at Hospital Sant Joan de Déu, Barcelona, from January 2000 to January 2023. Patient characteristics at diagnosis, first-line treatment, relapse patterns, and CNS metastasis management were analyzed in search of risk variables and survival outcomes. Results: CNS metastases at relapse were identified in 39/185 (21.1%) patients. Median age at diagnosis was 2.7 years, and 24/39 male. Stage 4 NB with multisite metastases accounted for most cases (92.2%). CNS events occurred predominantly at first relapse (29/39, 74.4%) and with neurological symptoms (23/38, 60.5%). MCYN amplification and concomitant extra-CNS metastases at CNS relapse were associated with poorer overall survival (OS) ( p=0.018 and p=0.0059, respectively). Neurological symptoms upon relapse significantly increased the risk for subsequent CNS events ( p=0.028). Curative-intent of treatment was attempted in 34/39 (87.2%) patients. After adjusting for immortal time bias, RT plus Omb significantly improved OS ( p<0.0001). Conclusions: In our experience, MYCN amplification and concomitant extra-CNS metastases at CNS relapse significantly decrease OS. Multimodal treatment including Omburtamab radioimmunotherapy significantly improves survival outcomes.

We report a new hyper unstable abnormal hemoglobin variant found in a Russian family. NGS revealed a new, previously unreported genetic variant in the 3’ exon of the β-globin gene [β141(H19)Leu-Pro (CTG>CCG); HBB: c.425T>C]. This variant was confirmed by Sanger sequencing in the patient and was not found in his parents. Capillary electrophoresis (CE) and reversed-phase high-performance liquid chromatography (RP-HPLC) were within normal limits. We named this hemoglobin variant Hb Yoshkar-Ola after the birthplace of the proband.

Background: The HIT-network was established in 2000 to create a population-based structure aiming to improve survival rates and reduce late effects for children with central nervous system (CNS) tumors by conducting comprehensive clinical trials. Methods: The HIT-network currently consists of 10 coordinating trial centers mandated by the German Society for Pediatric Oncology and Hematology (GPOH) to conduct clinical trials and research projects, and to provide counselling to local centers for individual patients. The network is complemented by 11 reference centers (neuropathology, tumor biology, neuroradiology, pediatric neurosurgery, cerebrospinal fluid (CSF), assessments, radiotherapy, biology), biostatistical support, and currently 72 local treatment sites. Results: Numbers of children and adolescents with newly diagnosed CNS tumors registered to trials and registries increased from approximately 500 to more than 600 per year, corresponding to >95% of affected HIT-eligible children and adolescents in Germany. Clinical counselling and upfront reference assessments ensure homogeneous clinical standards and avoid inadequate treatment of individual patients. Since 2007, the established reference services have been partially re-funded by German health insurances. Discussion: The HIT-network provides a unique structure for population-based state-of-the-art diagnostic assessments, treatment recommendations and counselling. It increases the ‘a priori’ accuracy of stratification parameters, and the timely inclusion into clinical trials and tumor-specific registries. Favorable outcomes are achieved within the trials and registry landscape e.g. through consistent reference assessments, reducing the gap to real world data. Resulting data facilitate representative, unbiased high-quality research projects across all CNS tumor entities. Interdisciplinary cooperation and competitive scientific output are enhanced.

Sickle cell acute pain crisis increase in frequency with age, and some patients develop chronic pain. Currently there are guidelines for management of acute pain crisis, but not for chronic pain. Chronic pain management defaults to long-term opioid therapy. Buprenorphine is a partial opioid agonist, a potent analgesic, with a respiratory ceiling effect. It may provide analgesic benefit and a ‘harms reduction approach’ in the management of chronic pain in pediatric patients with sickle cell disease. Buprenorphine is increasingly used in adult patients with sickle cell disease. We describe the inpatient micro-induction protocol we implemented in our pediatric center.

Background: Adherence to follow-up visits is crucial for optimizing clinical outcomes in paediatric patients with sickle cell disease (SCD). This study aimed to evaluate compliance with follow-up visits among paediatric SCD patients over a five-year period. Methodology: A retrospective analysis was conducted using data from the sickle cell disease clinic of Nnamdi Azikiwe University Teaching Hospital, spanning from January 2015 to December 2019. A total of 271 unique paediatric patients with SCD and 1117 follow-up visits were included. Compliance with follow-up visits, defined as attendance within 100 days of the previous visit, was assessed using Kaplan-Meier curves and Cox regression analysis. Results: During the study period, a total of 1117 follow-up visits were documented among 271 children diagnosed with sickle cell anaemia. The median age of the study cohort was 8 years (IQR: 4 to 12 years). Male patients constituted 57% of the study population. Fifty percent of subjects remained compliant with follow-up visits at 14.2 months (95% CI = 8.9-24.1 months) and this compliance decreased to 40% at 24 months (95% CI = 31-49 months). Males showed a lower likelihood to be compliant to follow-up visits than females (HR: 0.83; CI: 0.56-1.23). Following adjustments, patients who were sicker and young adolescents (10 to 14 years) had an increased likelihood of complying to follow up visits (HR: 1.05; CI: 0.71-1.57 vs HR: 1.15; CI: 0.682-1.940 respectively) but this was not statistically significant. Conclusion: The overall poor compliance rate to follow up visits underscores the urgent need for interventions aimed at improving adherence to follow-up visits in this vulnerable population. Counselling interventions and further exploration of factors influencing compliance are warranted to enhance the management and outcomes of children living with sickle cell anaemia.

A document by Gail Budhu. Click on the document to view its contents.

Practical Challenges Associated with Efanesoctocog Alfa (ALTUVIIIO) Prophylaxis in a 19-month-oldwith Severe Hemophilia AJessica N. Mistretta1, Maria G. Español1,2, Michael D. Tarantino1,2, Dane C. Christ1, Maureen D. Jones1,Jonathan C. Roberts1,21Bleeding & Clotting Disorders Institute, Peoria IL USA2Departments of Pediatrics and Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL USA