Side effects following COVID-19 vaccination in pediatric patients with sickle cell disease.

Vulnerable patient populations have seen decreased rates of vaccination against SARS-CoV2-19 (COVID-19) due to hesitancies and distrust, magnified by a paucity of data for certain populations. The rate of COVID-19 vaccination in children with sickle cell disease (SCD) remains low despite the risk for severe complications, resulting in continued infections and hospitalizations from COVID-19. We sought to describe vaccine reactions, including vaso-occlusive crises, emergency department visits, and hospitalizations, in children with SCD. Our findings will start to provide the necessary vaccine side effect data to inform patients, caregivers, and clinicians considering the COVID-19 primary vaccination series.

Side Effects With a Focus on Lymphadenopathy Following COVID-19 Vaccination in Pediatric and AYA Oncology Patients.

The Coronavirus Disease 2019 (COVID-19) pandemic led to the swift development of multiple vaccinations. Vaccine side effects were well-documented in the healthy adult cohort and included fever and lymphadenopathy, however, side effects in the pediatric immunocompromised population have not been reported. This retrospective study investigated vaccine-eligible children and adolescent young adult oncology patients 12 to 35 years old. We found uncommon, mild, and self-limiting side effects among pediatric cancer patients and survivors. This data will help guide pediatric and AYA oncologists in providing anticipatory guidance and serve as a guide to managing lymphadenopathy as a potential confounder of malignancy.

Secondary impacts of constipation in acute lymphoblastic leukemia in U.S. children's hospitals.

BACKGROUND: Childrenwith acute lymphoblastic leukemia (ALL) suffer a litany of chemotherapy-induced side effects. Constipation secondary to vinca alkaloids, psychological stressors, and opioid use are common issues for children newly diagnosed with leukemia. This study investigated the morbidity associated with constipation including infections, mucositis, and healthcare utilization in hospitalized children with ALL receiving induction chemotherapy. METHODS: We analyzed data from 48 children's hospitals in the Pediatric Health Information System, extracting patients 1-21 years of age with ALL, hospitalized for induction from October 2015 through December 2019. Data were analyzed using nonparametric statistics, and comparisons of outcomes between those with and without constipation were presented as adjusted odds ratios (aOR). RESULTS: We identified 2586 (56%) patients with constipation out of a total of 4622 unique ALL patients in induction. Compared to patients without constipation during induction, patients with constipation were significantly more likely to have mucositis (aOR = 2.30; p = 0.0010), perirectal issues (aOR = 3.21; p = 0.0092), or abdominal radiograph exposure (aOR = 2.40; p < 0.0001). The median length of induction hospitalization was significantly greater in those with constipation compared to those without constipation (10 days vs. 8 days; p < 0.0001). CONCLUSIONS: Children with ALL suffering from constipation during induction therapy have increased length of stay, mucositis, imaging, and overall healthcare utilization compared to children without constipation. Further research should explore the causative relationship between constipation and infections. Increased attention should be given to constipation management in patients with ALL at the start of induction therapy, particularly in patients with complications or prolonged hospitalizations.

Supportive care and osteopathic medicine in pediatric oncology: perspectives of current oncology clinicians, caregivers, and patients.

BACKGROUND AND OBJECTIVE: Many children receiving chemotherapy struggle with therapy-induced side effects. To date, there has been no literature investigating the needs, knowledge, or implementation of osteopathic manipulative treatments (OMT) as a supportive care option in pediatric oncology. We hypothesized that pediatric oncology clinicians, caregivers, and patients have (a) limited knowledge of OMT and (b) dissatisfaction with current supportive care options and (c) would be interested in having OMT available during chemotherapy, once educated. METHODS: Participants included three cohorts: (1) children aged ≥ 9 years, diagnosed with cancer and actively receiving chemotherapy; (2) their caregivers; and (3) oncology clinicians at Nationwide Children's Hospital. Participants completed 1:1 semi-structured interviews, which were audio-recorded, transcribed, and analyzed for thematic content regarding their perception of supportive care measures and views on OMT. Quantitative data was summarized descriptively. RESULTS: A total of 60 participants completed the interview. Participants demonstrated limited awareness of osteopathic medicine; no participant had more than "some" knowledge of OMT. After education about OMT using a brief video, all clinicians, caregivers, and 95% of patients were receptive to OMT as a supportive care option. Major themes included the following: (a) patients have uncontrolled chemotherapy side effects, (b) improved supportive care options are desired, and (c) osteopathic medicine is a favorable supportive care adjunct. CONCLUSIONS: Pediatric oncology clinicians, caregivers, and patients reported a need for better management of chemotherapy-associated side effects and an interest in utilizing OMT. These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology clinical setting.

Catheter-directed thrombolysis for submassive pulmonary embolism in children: A case series.

Incidence of venous thromboembolism, including pulmonary embolism (PE), continues to rise in children. Optimum management of submassive PE is unclear. The principal objective of this retrospective study was to investigate the radiological and clinical outcomes in children with submassive PE treated with catheter-directed thrombolysis (CDT). Five patients underwent six episodes of CDT. No patient developed major/clinically relevant non-major bleeding. Most patients had complete radiological thrombus resolution and no patient had evidence of chronic thromboembolic pulmonary hypertension. There is an urgent need for larger prospective cohort studies/randomized controlled trials to investigate the role of CDT in pediatric PE.

Prevalence and management of constipation in pediatric acute lymphoblastic leukemia in U.S. children's hospitals.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) suffer from a litany of chemotherapy-induced side effects. Constipation secondary to vinca alkaloids, environmental changes, and opioid use is a common issue for children newly diagnosed with leukemia. PROCEDURE: We analyzed data from 48 children's hospitals in the Pediatric Health Information System, extracting patients 1-21 years of age with ALL hospitalized from October 2015 through September 2019. Our objective was to investigate the prevalence, risk factors, and treatment of constipation in hospitalized children with ALL. RESULTS: We identified 4647 unique patients with an ALL induction admission. Constipation was the most common gastrointestinal diagnosis with 1576 (33.9%; 95% confidence interval [CI]: 32.6%-35.3%) patients diagnosed during induction admission and 19.8% in post-induction admissions. The most commonly administered constipation medications were poly-ethyl glycol (n = 3385, 89.6%), followed by senna (n = 1240, 32.8%), lactulose (n = 916, 24.2%), and docusate (n = 914, 24.2%). Multivariate logistic regression revealed the following variables to be significantly associated with the presence of a constipation diagnosis: age < 6 years at induction (compared with those ≥12 years; odds ratios [OR] = 1.32 [95% CI: 1.13-1.55]; P = < 0.001), female sex (OR = 1.16 [95% CI: 1.02-1.31]; P = 0.024), increased length of hospitalization (OR = 1.03 [95% CI: 1.02-1.04]; P < 0.0001), use of non-fentanyl opioids for one or two days (OR = 1.28 [95% CI: 0.99-1.65]; P = 0.056), and use of non-fentanyl opioids > 2 days (OR = 1.53 [95% CI: 1.19-1.95]; P < 0.001). CONCLUSIONS: A large portion of hospitalized children with ALL experience constipation and required medications. Increased attention should be paid to constipation prophylaxis and treatment in ALL patients, particularly at the start of induction therapy.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

CONTEXT: Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. OBJECTIVES: The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. METHODS: This is a prospective, single-institution pilot study evaluating children and AYAs aged ≥2 years to ≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. RESULTS: A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). CONCLUSIONS: Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.

The pediatric approach to Hodgkin lymphoma.

Hodgkin lymphoma (HL) occurs throughout the lifespan but is one of the most common cancers in adolescents and young adults (AYA; 15-39 years). HL has become a highly curable disease with survival rates surpassing 90%, including patients with high-risk and advanced stage disease. Unfortunately, intensive treatment carries a risk of short- and long-term toxicity. Given the decades pediatric HL survivors are expected to live after treatment, the pediatric approach to treatment has focused on improving the therapeutic index through response adapted treatment and more recently the incorporation of novel agents. The efforts of pediatric and medical oncologists in research and clinical trial development have long occurred in parallel, but recent efforts have laid the foundation for collaboration with the goal of standardizing AYA care and allowing earlier incorporation of novel therapy for younger patients. This review focuses on the evolution of the management of pediatric HL including epidemiology, biology, and approaches to upfront and salvage treatment regimens.

An International Survey Investigating the Incidence and Management of Brown Fat Uptake on 18F-FDG PET/CT at Children's Hospitals and Interventions for Mitigation.

Brown fat can present challenges in patients with cancer who undergo 18F-FDG PET scans. Uptake of 18F-FDG by brown fat can obscure or appear similar to active oncologic lesions, causing clinical challenges in PET interpretation. Small, retrospective studies have reported environmental and pharmacologic interventions for suppressing brown fat uptake on PET; however, there is no clear consensus on best practices. We sought to characterize practice patterns for strategies to mitigate brown fat uptake of 18F-FDG during PET scanning. Methods: A survey was developed and distributed via e-mail LISTSERV to members of the Children's Oncology Group diagnostic imaging committee, the Society for Nuclear Medicine and Molecular Imaging pediatric imaging council, and the Society of Chiefs of Radiology at Children's Hospitals between April 2022 and February 2023. Responses were stored anonymously in REDCap, aggregated, and summarized using descriptive statistics. Results: Fifty-five complete responses were submitted: 51 (93%) faculty and fellow-level physicians, 2 (4%) technologists, and 2 (4%) respondents not reporting their rank. There were 43 unique institutions represented, including 5 (12%) outside the United States. Thirty-eight of 41 (93%) institutions that responded on environmental interventions reported using warm blankets in the infusion and scanning rooms. Less than a third (n = 13, 30%) of institutions reported use of a pharmacologic intervention, with propranolol (n = 5, 38%) being most common, followed by fentanyl (n = 4, 31%), diazepam (n = 2, 15%), and diazepam plus propranolol (n = 2, 15%). Selection criteria for pharmacologic intervention varied, with the most common criterion being brown fat uptake on a prior scan (n = 6, 45%). Conclusion: Clinical practices to mitigate brown fat uptake on pediatric 18F-FDG PET vary widely. Simple environmental interventions including warm blankets or increasing the temperature of the injection and scanning rooms were not universally reported. Less than a third of institutions use pharmacologic agents for brown fat mitigation.

Implementation of an Anterior Mediastinal Mass Pathway to Improve Time to Biopsy and Multidisciplinary Communication.

Background: Mediastinal masses in children with cancer present unique challenges, including the risk of respiratory and hemodynamic compromise due to the complex anatomy of the mediastinum. Multidisciplinary communication is often a challenge in the management of these patients. After a series of patients with mediastinal masses were admitted to Riley Hospital for Children Pediatric Intensive Care Unit, the time from presentation to biopsy and pathology was greater than expected. We aimed to reduce the time to biopsy by 25% and demonstrate improved multidisciplinary communication within 6 months of protocol implementation for patients presenting to Riley Hospital for Children Emergency Department with an anterior mediastinal mass. Methods: Quality improvement methodology created a pathway that included early multidisciplinary communication. The pathway includes communication between the emergency department and multiple surgical and medical teams via a HIPPA-compliant texting platform. Based on patient stability, imaging findings, and sedation risks, the approach and timing of the biopsy were determined. Results: The pathway has been used 20 times to date. We successfully reduced the time to biopsy by 38%, from 25.1 hours to 15.4 hours. There was no statistically significant reduction in time to pathology. The multidisciplinary team reported improved communication from a baseline Likert score of 3.24 to 4. Conclusions: By initiating early multidisciplinary communication, we reduced the time to biopsy and pathology results, improving care for our patients presenting with anterior mediastinal masses.

Protocol-Stipulated Dose Modification to Manage Chemotherapy-Induced Peripheral Neuropathy in Children, Adolescents, and Young Adults With High-Risk Hodgkin Lymphoma.

PURPOSE: Brentuximab vedotin (BV) incorporation into frontline chemotherapy regimens improved outcomes for classic Hodgkin lymphoma (cHL). The shared mechanism of action of BV and vinca alkaloids as microtubulin inhibitors increased the potential risk of chemotherapy-induced peripheral neuropathy (CIPN). Rates of CIPN and use of protocol-stipulated dose modifications of a microtubulin inhibitor were examined on the Children's Oncology Group AHOD1331 study, which compared BV, doxorubicin, vincristine (VCR), etoposide, prednisone, cyclophosphamide (BV-AVE-PC; BV arm) with bleomycin containing doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC; standard arm) in patients with high-risk cHL ages 2-21 years. METHODS: AHOD1331 required clinician grading and reporting of ≥grade 2 CIPN. Protocol-stipulated dose modifications of VCR preceded modification of BV for ≥grade 2 CIPN in the BV arm, but only required modification of VCR for ≥grade 3 in the standard arm. Outcomes included CIPN rates, dose modification of microtubulin inhibitors by study arm, clinical factors associated with dose modifications, and event-free survival (EFS) by the presence of dose modification. RESULTS: Among the 582 patients who began protocol therapy, 112 developed ≥grade 2 CIPN. Cumulative incidence of CIPN did not differ by study arm (19.2 v 19.8%, P = .91). CIPN dose modifications occurred more frequently in the BV arm (9.5% v 2.8%, P = .001); however, most patients with CIPN on the BV arm received full-dose BV. EFS did not differ by the presence of dose modifications after accounting for study arm, age, sex, and stage, although older age was significantly associated with the risk of VCR dose modifications for CIPN. CONCLUSION: A staged dose modification plan for vinca alkaloids and BV as administered in AHOD1331 minimized the effect of incorporating a second microtubulin inhibitor on CIPN without compromising treatment efficacy in the BV arm.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

PURPOSE: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Diagnosis and management of Hodgkin lymphoma in children, adolescents, and young adults.

Advances in the management of Hodgkin lymphoma in children, adolescents and young adult have resulted in survival outcomes exceeding 90%. The risk of late toxicity, however, remains a significant concern for survivors of HL and the focus of modern trials have been to advance cure rates while reducing long term toxicity. This has been accomplished through response-adapted treatment approaches and the incorporation of novel agents, many of which target the unique interaction between the Hodgkin and Reed Sternberg cells and the tumor microenvironment. In addition, an improved understanding of prognostic markers, risk stratification, and the biology of this entity in children and AYAs may allow us to further tailor therapy. This review focuses on the current management of HL in the upfront and relapsed settings, recent advances in novel agents that target HL and the tumor microenvironment, and promising prognostic markers that may help guide the future management of HL.

Late effects and frontline treatment selection for children with non-Hodgkin lymphoma.

Approximately 1 in 640 adults between 20 and 40 years of age is a survivor of childhood cancer. However, survival has often come at the expense of increased risk of long-term complications, including chronic health conditions and higher mortality rates. Similarly, long-term survivors of childhood non-Hodgkin lymphoma (NHL) experience significant morbidity and mortality related to prior cancer treatments, highlighting the importance of primary and secondary prevention strategies to mitigate late toxicity. As a result, effective treatment regimens for pediatric NHL have evolved to reduce both short- and long-term toxicity through cumulative dose reductions and elimination of radiation. The establishment of effective regimens facilitates shared decision-making opportunities for frontline treatment selection that considers efficacy, acute toxicity, convenience, and late effects of treatments. The current review seeks to merge current frontline treatment regimens with survivorship guidelines to enhance understanding of potential long-term health risks to facilitate best treatment practices.

Investigating the safety and feasibility of osteopathic medicine in the pediatric oncology outpatient setting.

CONTEXT: Pediatric patients receiving chemotherapy experience unwanted therapy-induced side effects, commonly constipation and pain that diminish quality of life. To date, few studies have investigated the safety and feasibility of osteopathic manipulative treatment (OMT) in pediatric oncology. OBJECTIVES: The primary objective of this study is to investigate the safety and feasibility of OMT in pediatric oncology outpatient clinics. METHODS: This is a single institutional pilot study evaluating children aged ≥2-21 years receiving chemotherapy for an oncological diagnosis at Nationwide Children's Hospital (NCH). Permission was obtained from the NCH Institutional Review Board. Participants were enrolled for 8 weeks and received weekly OMT. OMT was deemed feasible by participating in six out of eight weekly treatments, and safety was assessed through adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE). During the clinic visit, patients answered validated surveys on constipation (Bristol Stool Scale) and pain (FACES Scale) pre/post-OMT. Feasibility was analyzed utilizing a one-sided exact binomial test while validated tools and adverse events were summarized descriptively. RESULTS: A total of 23 patients were enrolled, with 21 included in feasibility analyses. The majority of the patients were female (n=13, 61.9%), with a median age of 12 years at enrollment (range, 2.7-20.8 years). There were no serious adverse events attributed to OMT intervention, and among the patients assessed for feasibility, 100% of them participated in at least two-thirds of their weekly OMT treatments, meeting our defined feasibility criteria. The intervention lasted an average of 14.2 min (range, 7.2-19.2 min). There were no FACES or Bristol Stool Scale scores that correlated with worsening pain on constipation post-OMT intervention. CONCLUSIONS: Pediatric oncology patients were feasibly and safely able to receive OMT during a regularly scheduled chemotherapy visit. The limitations include the small sample size. These findings support the need to further investigate the safety and feasibility, as well as efficacy, of OMT in the pediatric oncology clinical setting.

Constipation and GI diagnoses in children with solid tumours: prevalence and management.

OBJECTIVES: Despite continued development of targeted therapies for children with cancer, patients continue to experience an array of unwanted side effects. Children with solid tumours may experience constipation as a result of vinca alkaloid therapy, psychological stressors, periods of inactivity and opioid use. Our objective was to investigate the prevalence and treatment of constipation in hospitalised children with solid tumours treated with chemotherapy. METHODS: We retrospectively analysed data from 48 children's hospitals in the Pediatric Health Information System, extracting patients 0-21 years of age with a solid tumour diagnosis hospitalised from October 2015 through December 2019. RESULTS: We identified 13 375 unique patients with a solid tumour diagnosis receiving chemotherapy. Constipation was the most common gastrointestinal complaint with 8658 (64.7%; 95% Cl: 63.9% to 65.5%) having a constipation diagnosis or having received at least two laxatives during admission. Bone cancers had the highest percentage (69.9%) of patients with constipation, while Hodgkin's lymphoma had the lowest, although 52.1% of patients were affected. A total of 44% (n=35 301) of encounters received an opioid at some point during admission. Of patients receiving constipation medications, the most commonly prescribed was polyethyl glycol (n=25 175, 31.7%), followed by docusate (n=11 297, 14.2%), senna (n=10 325, 13.0%) and lactulose (n=5501, 6.9%). CONCLUSIONS: Constipation is the most common gastrointestinal issue that children with solid tumours experience while receiving chemotherapy in the inpatient setting. Increased attention should be given to constipation prophylaxis and treatment in children with solid tumours undergoing chemotherapy, particularly those identified as high risk.

Caregiver Perspectives on Patient Participation in Biological Pediatric Cancer Research.

Adolescent cancer patients and their caregivers have demonstrated willingness to participate in invasive biological sampling, either for their own potential benefit or for research purposes. However, many malignancies occur primarily in prepubescent patients and there are no similar studies in this population. Our study objective was to assess the willingness of caregivers to consent to research studies involving invasive biological sampling in children ≤ 13 years of age. Participants completed a survey assessing their willingness to allow various procedures both with and without clinical benefit to their children. Most respondents were willing to allow additional blood draws regardless of potential benefit to their children (95.6% were willing when there would be benefits and 95.6% were willing when there would not). Although the overall willingness was lower with other hypothetical procedures, the majority of respondents were still willing to allow additional biopsies for research purposes. Caregivers of young children with cancer will allow their children to undergo additional invasive procedures for research purposes. This willingness decreased with more invasive procedures without potential direct benefit, but interest remained in more than half of participants. Caregivers for young patients with cancer should be approached for participation in future biological/correlative studies.