Pain is a common and clinically significant complication of pediatric hematopoietic cell transplantation (HCT). It evolves across conditioning, engraftment, early recovery, and survivorship, and may result from mucosal injury, procedures, graft-versus-host disease (GVHD), infection, medication toxicity, immobility, and long-term complications. Pediatric HCT-specific guidance remains limited, so practice is often extrapolated from broader pediatric oncology, adult HCT, and supportive/palliative care literature. This narrative review summarizes major pain phenotypes after pediatric HCT and emphasizes developmentally appropriate, repeated assessment; phenotype-based pharmacologic management; and multimodal care integrating opioids, adjuvant analgesics, nonpharmacologic strategies, rehabilitation, child life, psychology, pharmacy, and palliative care. Evidence remains fragmented. Future work should prioritize standardized pain phenotyping, patient- and proxy-reported outcomes, longitudinal assessment of pain and function, and multicenter supportive-care pathways extending beyond acute transplant.
BACKGROUND:Pediatric hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that can be classified into three principal etiologies (primary HLH [pHLH], Epstein-Barr-virus-driven HLH [EBV-HLH], and secondary HLH [sHLH]) and is associated with disparate outcomes. Treatment escalation decisions remain largely empirical, guided by clinical presentation and conventional laboratory results rather than by an integrated biomarker framework. PROCEDURE:We prospectively enrolled 180 consecutive pediatric patients with HLH at Children's Hospital 1, Ho Chi Minh City, Vietnam (October 2022-October 2025): pHLH, n = 40; EBV-HLH, n = 46 (CD27 intact, n = 19; CD27 dim, n = 27); and sHLH, n = 94. A 15-analyte multiplex cytokine panel and six-marker lymphocyte subset flow cytometry were performed at diagnosis (T0) and Day 7 (T1). Logistic regression models were developed and internally validated using bootstrap optimism correction (1000 iterations), 5-fold stratified cross-validation, and a temporal split. RESULTS:Overall mortality was 31.1% (EBV-HLH 67.4%, pHLH 45.0%, and sHLH 7.4%). Three discrete cytokine and subset phenotypes emerged: EBV-HLH showed massive elevations in IFN-γ and sCD25, with profound CD4+ and double-negative T-cell depletion; pHLH showed elevated tumor necrosis factor-α with preserved subsets; sHLH had low-amplitude profiles with the highest CD4+ counts. Day-7 IFN-γ T1/T0 ratio (threshold 0.376) stratified mortality 6- to 27-fold within each etiology. Cytokine drivers of escalation were etiology specific (sCD25 in pHLH, sCD25+IL-18 in EBV-HLH, and IL-10/IL-6 in sHLH). The integrated three-component model achieved an apparent AUC of 0.963, a bias-corrected AUC of 0.947 (95% CI: 0.92-0.97), a 5-fold CV AUC of 0.942 ± 0.05, and a temporal validation AUC of 0.946-all three methods were convergent. CONCLUSIONS:Integrating etiology, cytokine phenotype, and lymphocyte subset profile provides biology-grounded prediction of mortality and treatment escalation in pediatric HLH. Multicenter external validation is the next essential step.
BACKGROUND:Patients with vascular malformations (VMs) experience a wide spectrum of symptoms including pain, physical impairment, bleeding, thrombosis and psychosocial problems. The occurrence of pain in these patients might be caused by thrombosis or phleboliths (due to venous stasis), ischemia, or neuropathy. We aimed to assess the frequency of pain in patients with low-flow VM and to study its association with laboratory markers and radiological evidence of thrombosis. PATIENTS AND METHODS:A cross-sectional study that included 30 patients (12 female and 18 male) with low-flow VM. Medical records were reviewed for demographic data and details of VM. Assessment of pain was done by using the Face, Legs, Activity, Cry, Consolability (FLACC) scale and by the Wong-Baker FACES pain rating scale for patients 3 years or older. Markers of thrombosis including D-dimer level were measured. Results of radiologic investigations including Doppler ultrasonography and magnetic resonance imaging (MRI) were collected. RESULTS:The median age of patients was 51.4 months. Of 30 patients, 16 had VMs, 6 patients had lymphatic malformations and 8 had combined malformations. Eleven patients had thrombi or phlebolith by Doppler ultrasound or MRI. Pain was reported by 25 (83%) patients (acute pain in 11 and chronic pain in 14). D-dimer levels were highest in patients with acute pain (median level 1337 ng/mL) compared to those with chronic or no pain (p = 0.002). All 11 patients who had thrombi or phlebolith by Doppler ultrasound or MRI reported pain (6 with acute and 5 with chronic pain). CONCLUSION:Acute pain in patients with low-flow VMs with venous component is associated with high D-dimer and intralesional thrombosis by Doppler ultrasound.
BACKGROUND:Pediatric thromboembolism is increasingly encountered in critical care. Systemic thrombolysis with tissue plasminogen activator (tPA) facilitates vessel or valve patency, yet pediatric-specific protocols remain undefined, and safety concerns persist. OBJECTIVE:To evaluate the efficacy and safety of a tailored, prolonged systemic tPA protocol for vessel thrombosis and mechanical valve obstruction in infants and children, and to characterize D-dimer kinetics by indication. METHODS:This retrospective cohort study was performed in a tertiary pediatric cardiac ICU (from July 2014 to March 2024). Extracted data included demographics, tPA dosing, laboratory trends, transfusion requirements, imaging-confirmed success, and adverse events. D-dimer trajectories were analyzed using Welch's t-test. RESULTS:Twenty-two patients received systemic tPA during the study period. Median age was 287 days (IQR: 64.8-940); 32% were less than 90 days old. Indications included stuck mechanical valve (n = 10), central venous thrombosis with chylothorax (n = 7), large venous thrombosis (n = 3), coronary thrombosis (n = 1), and arterial ischemic stroke (n = 1). Median initial tPA dose was 0.1 mg/kg/h (IQR: 0.06-0.1), with escalation up to 0.5 mg/kg/h in selected cases; mean treatment duration was 3.9 ± 2.8 days. Valve mobility was restored in 80%. Complete thrombus resolution was achieved in all venous, coronary, and stroke cases. Minor bleeding occurred in 23%; one subdural hemorrhage (5%) was observed. All patients survived to discharge. D-dimer kinetics differed significantly between vessel thrombosis and mechanical valve obstruction (p < 0.01), demonstrating distinct fibrinolytic profiles. CONCLUSIONS:Tailored prolonged systemic tPA appears effective with minimal adverse effects when administered under strict monitoring. Distinct D-dimer patterns may aid treatment guidance. Multicenter studies are needed to validate standardized pediatric protocols.
BACKGROUND:We present an update on the status, needs and challenges faced by paediatric imaging and radiotherapy (RT) programmes globally after a previous survey conducted by the International Atomic Energy Agency (IAEA) 10 years prior. METHODS:We developed and distributed a 121-question survey to radiation oncologists, medical physicists and radiologists from participating Member States (MSs). It included questions on radiation oncology, imaging, nutrition, human capacity to support these services, quality assurance practices and other aspects of childhood cancer management. Questions evaluated practices, access, standards and other topics specific to childhood cancer care. RESULTS:Forty-seven IAEA MSs completed the survey. Regardless of country income level, most institutions had departments providing essential services of paediatric oncology, anaesthesia and radiology. Disparities in access exist regarding nuclear medicine, advanced diagnostic and interventional radiology, linear accelerators, quality assurance and services for patients and families favouring higher-income countries. Medical physics presence for radiation oncology was consistent across income level, whereas access to it was scarce. Regarding diagnostic imaging, most respondents reported access to computed tomography but access to other advanced imaging technologies was limited. CONCLUSIONS:While there have been improvements in access to certain aspects of paediatric cancer care compared to the previous survey, disparities persist, particularly in low- and middle-income countries. There is a need for more specialized training, better access to imaging and RT technology, and improved ancillary services. These findings can inform policy and decision-making authorities towards the WHO's 2030 goal for childhood cancer.
BACKGROUND:The Standards for Psychosocial Care for Children with Cancer and Their Families ("Standards") are evidence-based guidelines for psychosocial care in pediatric oncology. Care related to the three "Asking and Monitoring" Standards-Assessment of Psychosocial Needs, Assessment of Financial Needs, and Monitoring Neurocognitive Problems-is frequently provided, but community member input regarding the implementation of this care is notably absent in extant literature. The Implementing the Standards Together: Engaging Parents and Providers in Psychosocial Care (iSTEPPP) team conducted a mixed-methods, community-engaged study to understand parent and provider perceptions and prioritization of these three Standards. METHODS:A two-round Delphi technique identified consensus on prioritization of the Standards by pediatric oncology providers (medical and psychosocial) and parents. The survey included optional free-text responses to explain their reasoning for their selections. Data were analyzed using an iterative qualitative process. RESULTS:Responses were included from 129 parents and 62 providers. For Assessment of Psychosocial Needs and Assessment of Financial Needs, parent responses focused on immediate consequences when the Standards are not provided, while providers described their relevance to broader medical and psychosocial outcomes. For Monitoring Neurocognitive Problems, providers noted its importance because families prioritize it, while parents reflected on a lack of understanding and attention to neurocognitive deficits. CONCLUSION:While parents shared concerns about both immediate and long-term consequences if Standards-aligned care is not delivered, providers emphasized broader or longer term consequences. Findings reflect the critical importance of frequent, structured monitoring of psychosocial and financial needs and more comprehensive monitoring for neurocognitive deficits.
Safe and effective use of voriconazole in children necessitates therapeutic drug monitoring (TDM) of serum concentrations given the pharmacokinetic variability amongst these patients. Informed by an internal review of voriconazole TDM practices revealing suboptimal performance, our aim was to improve the proportion of voriconazole TDM obtained as a trough at steady state (trss). Revision to our internal lab order and creation of a triazole TDM guidance document resulted in a higher proportion of voriconazole trss. These interventions are a first step to future improvement in time to therapeutic voriconazole trss in pediatric patients.
BACKGROUND AND PURPOSE:Total body irradiation (TBI) is a standard component of conditioning regimens for pediatric patients with acute lymphoblastic leukemia (ALL) undergoing hematopoietic stem cell transplantation (HSCT). Volumetric modulated arc therapy (VMAT) has emerged as a promising technique to improve dose conformity and organ-at-risk (OAR) sparing. This study evaluates the feasibility, dosimetric performance, and acute toxicity of a VMAT-based TBI (VMAT-TBI) technique implemented in a pediatric population. MATERIALS AND METHODS:Fifteen pediatric patients treated with myeloablative VMAT-TBI between August 2019 and December 2024 were retrospectively analyzed. Prescription regimens ranged from 9.9 to 12 Gy, delivered in three to six fractions. Planning objectives followed ESTRO-ACROP-SIOPE recommendations, with mean lung dose less than 8 Gy and mean kidney dose less than 10 Gy. Dosimetric coverage, OAR sparing, patient-specific quality assurance, image-guided verification, and clinical outcomes were assessed. RESULTS:All treatment plans achieved adequate target coverage (mean PTV D95% = 96.6% ± 2.5%), with V110% = 19.1% ± 11.2% and V120% less than 1%. Mean lung and kidney doses were 7.8 ± 0.7 and 8.9 ± 1.1 Gy, respectively. Planned and measured dose distributions showed excellent agreement (gamma passing rates with 3%/3 mm criteria of 96.2% ± 4.6% with ArcCHECK diode array). After a median follow-up of 18 months, one late non-infectious pulmonary toxicity and one severe renal toxicity were observed. CONCLUSION:VMAT-TBI is a feasible, effective technique for pediatric HSCT conditioning, providing excellent target coverage, OAR sparing, and acceptable toxicity. These findings support VMAT-TBI as a viable alternative to conventional TBI.
Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are aggressive malignancies in children and adolescents where metastases impact prognosis. 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) and bone marrow aspirate and trephine biopsies (BMAT) are used to identify disease involvement. Literature suggests that BMAT may not be required for staging when FDG-PET/CT is performed in ES. However, BMAT continues to be performed. This retrospective audit re-reviewed staging practices in the ES cohort to confirm the applicability of existing evidence and extended the analysis to include patients with RMS, where there is comparatively less evidence. This review provides insight into whether reduction in investigations is feasible in the broader sarcoma population. A total of 240 patients with histologically confirmed ES (128) or RMS (112) diagnosed between 2006 and 2020 were reviewed. A total of 133 patients met inclusion criteria. The sensitivity of FDG-PET/CT for bone marrow involvement for all patients was 92%, and the negative predictive value of FDG-PET/CT was 99%. The sensitivity and negative predictive value were each 100% in the ES group and 88% and 98%, respectively, in the RMS group. This suggests that FDG-PET/CT is adequate in identifying patients who do not have bone marrow involvement. Thus, we propose if marrow disease is not identified on FDG-PET/CT, a BMAT could be omitted from the patient's workup.
Hypersensitivity reactions with pegylated Escherichia coli-derived asparaginase formulations are frequent and can complicate delivery of intended therapy for patients with acute lymphoblastic leukemia (ALL). On DFCI 16-001, which enrolled patients aged 1-21 years with newly diagnosed ALL, we piloted pegaspargase rechallenge after Grade 2 hypersensitivity reaction, including premedication and serum asparaginase activity (SAA) assessment. Among those who underwent rechallenge, the rechallenge dose was successfully administered (without reaction and with adequate SAA) in 41.3% of patients. This approach reduces the number of patients requiring switch to alternative asparaginase formulations, which have had limited availability and require frequent dosing.
We measured dasatinib concentrations in paired plasma and cerebrospinal fluid (CSF) samples from children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Blood samples were collected from children at 0 h (pre-dasatinib) and 2 h post-dasatinib, along with CSF. After validating a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for dasatinib in both matrices, we quantified drug concentrations in plasma and CSF and expressed blood-brain barrier penetration as the plasma-to-CSF concentration ratio. Twenty children with Ph+ ALL, who received oral dasatinib (60-80 mg/m2·day), were included in this study. The median age was 10.8 (5-16) years, with 13 males (65%) and 7 females (35%). In plasma, the mean dasatinib concentrations were 1.3 ± 0.7 ng/mL at 0 h and 101.6 ± 42.1 ng/mL at 2 h. In CSF, the mean dasatinib concentration was 0.5 ± 0.2 ng/mL at 2 h. The median paired plasma/CSF concentration ratio was 225:1 (98:1-406:1). In conclusion, despite therapeutic systemic levels, dasatinib penetrates poorly into CSF in children with Ph+ALL.
BACKGROUND:The WHO Global Initiative for Childhood Cancer (GICC) targets a global survival rate of 60% for childhood cancer, focusing initially on six common and curable cancers. This study assessed the risk of treatment abandonment (TxA) and the impact on survival of five of these cancers in sub-Saharan Africa in preparation for a cash transfer intervention. METHODS:This multi-centre, prospective, observational cohort study included newly diagnosed children (<16 years) with Burkitt lymphoma (BL), acute lymphoblastic leukaemia (ALL), Wilms tumour (WT), retinoblastoma (RB) or Hodgkin disease (HD), enrolled between January 2022 and April 2024 from hospitals in Ethiopia (n = 2) and Uganda. Event-free survival (EFS) was estimated using Kaplan-Meier methods, and the cumulative incidence of TxA was estimated using competing risks methods. RESULTS:Of 370 patients enrolled (median age 6 years, 62% boys), ALL was the most common diagnosis (30%, 112/370). Median follow-up was 26 months (range 6-35 months). The overall risk of treatment abandonment was 43%, ranging from 20% in Mbarara, Uganda to 54% in Gondar, Ethiopia. It was highest in patients with WT (48%) and RB (49%). Overall, 2-year EFS was 28% (confidence interval [CI] 24%-34%) with TxA as an event and 59% (53%-66%) when TxA cases were censored. CONCLUSION:The overall risk of treatment abandonment is high, 43%, in this baseline 'Zero Abandonment' study in participating hospitals in Ethiopia and Uganda. Treatment abandonment significantly affects survival, currently 28%, and potentially to increase to 59% if treatment abandonment was completely prevented.
OBJECTIVES:Rhabdomyosarcoma represents the most common paediatric soft tissue sarcoma, with 40% occurring in the head and neck region. Given that survival rates now reach 80%, minimising late adverse effects, particularly dental developmental complications, has become a priority. The aim of this paper was to identify the scope, severity and range of such late dental effects following treatment for head and neck sarcoma. MATERIALS AND METHODS:We systematically investigated late dental adverse events using orthopantomograms in rhabdomyosarcoma survivors treated between 1990 and 2014. Orthopantomograms were evaluated using a validated scoring system (DENTALE) that evaluates skeletal deformations, tooth presence, tooth wear, crown shape, eruption, root-crown ratio and root shape. RESULTS:Among 103 survivors (median age at diagnosis 5.4 years, 42.7% female), 92.2% exhibited dental adverse effects. Missing molars occurred in 45.6% of survivors. Root abnormalities were present in 72.8% of survivors, crown-to-root ratio abnormalities in 56.3% and eruption disturbances in 45.6%. Age at diagnosis was inversely correlated with total adverse effect score (rs = -0.389, p < 0.001). Survivors diagnosed before age 6 had significantly higher total dental adverse effect scores (p = 0.008), showing more effects of crowns (p = 0.016), crown-root ratio (p = 0.020), tooth eruption (p = 0.005) and roots (p = 0.006). CONCLUSION:This study demonstrates that rhabdomyosarcoma survivors are at substantial risk for a variety of dental developmental issues when treated at a younger age. Consequently, routine dental screening during follow-up is essential, with specialised dental and orthodontic care provided when clinically indicated.
