Treatment practices and response in kaposiform hemangioendothelioma: A multicenter cohort study.

BACKGROUND AND OBJECTIVES: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first-line therapy in the absence of available prospective clinical trials. METHODS: Patients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated. RESULTS: Of 159 unique KHE/TA subjects, Kasabach-Merritt phenomenon (KMP) was present in 64 (40.3%), and only two patients were deceased (1.3%). Over 60% (n = 96) demonstrated treatment response at 3 months, and more than 70% (n = 114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs. 20%, p = .03), but there were no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus. CONCLUSIONS: In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature, but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%), and there was no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.

Practice Variations in Managing Infantile Hemangiomas.

Infantile hemangioma (IH) is the most common benign tumor of infancy. For children with IH who require treatment, propranolol and other beta blockers have been shown to be safe and effective. Although consensus guidelines for managing IH have been published, anecdotal experience suggests that there remain variations in management. This study was performed to document these variations amongst providers and to identify areas for future research. We conducted an Internet-based survey of clinicians who treat patients with IH. Hypothetical cases and management scenarios were presented. Twenty-nine respondents participated in the survey. Most respondents use generic propranolol in infants with growing IH of the head and neck, with a goal dose of 2 mg/kg/d, until ~1 year of age. A variety of management strategies were documented including which patients should be treated, optimal dose and duration of therapy, how patients should be monitored, which patients should get additional workup, how propranolol should best be discontinued, and how often to see patients in follow-up. This study demonstrates wide practice variations in managing patients with IH. Further research is indicated to address these variations and develop additional/updated evidence-based guidelines.

Barriers to Genetic Testing in Vascular Malformations.

Importance: Vascular malformations (VMs) are rare disorders of vasculogenesis associated with substantial morbidity. Improved understanding of their genetic basis is increasingly guiding management, but logistical barriers to obtaining genetic testing in patients with VM may constrain treatment options. Objectives: To examine the institutional mechanisms for and obstacles to obtaining genetic testing for VM. Design, Setting, and Participants: This survey study invited members of the Pediatric Hematology-Oncology Vascular Anomalies Interest Group, representing 81 vascular anomaly centers (VACs) serving individuals up to 18 years of age, to complete an electronic survey. Respondents were mostly pediatric hematologists-oncologists (PHOs) but included geneticists, genetic counselors, clinic administrators, and nurse practitioners. Responses that were received between March 1 and September 30, 2022, were analyzed with descriptive methods. Requirements for genetic testing by several genetics laboratories were also reviewed. Results were stratified by size of the VAC. Main Outcomes and Measures: Vascular anomaly center and associated clinician characteristics and practice patterns for ordering and obtaining insurance approval for genetic testing for VMs were collected. Results: Responses were received from 55 of 81 clinicians, for a response rate of 67.9%. Most respondents were PHOs (50 [90.9%]). Most respondents (32 of 55 respondents [58.2%]) replied that they order genetic testing on 5 to 50 patients per year and reported a genetic testing volume increase of 2- to 10-fold over the past 3 years (38 of 53 respondents [71.7%]). Most testing was ordered by PHOs (35 of 53 respondents [66.0%]), followed by geneticists (28 [52.8%]) and genetic counselors (24 [45.3%]). In-house clinical testing was more common at large and medium-sized VACs. Small VACs were more likely to use oncology-based platforms, which potentially miss low-frequency allelic variants in VM. Logistics and barriers varied by size of the VAC. Obtaining prior authorization was the duty shared among PHOs, nurses, and administrative staff, but the burden of insurance denials and appeals were on PHOs (35 of 53 respondents [66.0%]). Lack of administrative support; unclear institutional, insurance, and laboratory requirements; and lack of clinician education were barriers to genetic testing at VACs of all sizes. The effort to obtain genetic testing for patients with VM, compared with patients with cancer, was perceived as excessive, despite genetic testing being considered standard of care for this population. Conclusions and Relevance: Results of this survey study showed the barriers to genetic testing for VM across VACs, described differences between VACs based on size, and proposed multiple interventions to support clinicians ordering genetic testing for VM. The results and recommendations should have broader application to clinicians caring for patients for whom molecular diagnosis is important to medical management.

Fertility Preservation Decisional Turning Points for Adolescents and Young Adults With Cancer: Exploring Alignment and Divergence by Race and Ethnicity.

PURPOSE: For adolescents and young adults (AYAs) with cancer, fertility preservation (FP) decision making is complex and distressing. Racial/ethnic minority (REM) AYAs experience disparities in FP awareness, uptake, and outcomes. A turning point (TP) is a point of reflection, change, or decisive moment(s) resulting in changes in perspectives or trajectories. To enhance understanding of AYAs' diverse experiences, this study examined alignment and/or divergence of FP decisional TPs among non-Hispanic White (NHW) AYAs and REM AYAs. METHODS: Qualitative semistructured interviews were conducted in person, by video, or phone with 36 AYAs (20 NHW and 16 REM [nine Hispanic and seven Black/multiracial Black). The constant comparative method was used to identify and analyze themes illustrating participants' conceptualization and/or experience of FP decisional TPs. RESULTS: Seven thematic TPs emerged: (1) emotional reaction to discovering FP procedures exist; (2) encountering unclear or dismissive communication during initial fertility conversations with health care providers; (3) encountering direct and supportive communication during initial fertility conversations with health care providers; (4) participating in critical family conversations about pursuing FP; (5) weighing personal desire for a child against other priorities/circumstances; (6) realizing FP is not feasible, and (7) experiencing unanticipated changes in cancer diagnosis or treatment plans/procedures. TP variations include REM participants reported dismissive communication and suggested cost was prohibitive. NHW participants emphasized more forcefully that biological children may become a future priority. CONCLUSION: Understanding how clinical communication and priorities/resources may vary for NHW and REM AYAs can inform future interventions aimed at reducing health disparities and enhancing patient-centered care.

Safety of propranolol for infantile hemangioma in infants less than five weeks corrected age.

BACKGROUND/OBJECTIVES: Propranolol is used to treat problematic infantile hemangiomas (IHs), but its safety in infants <5 weeks corrected age has not been established. The objective of this study was to assess the safety and efficacy of propranolol for treatment of IH in infants <5 weeks corrected age, or 45 weeks corrected gestational age (CGA). METHODS: We performed a single institution, retrospective review of patients treated with propranolol prior to the age of 6 months between 2017 and 2021. Patient characteristics, location of hemangioma(s), weight at initiation of treatment, dosing information, side effects, response, and duration of treatment were documented. RESULTS: Of 200 patients with IH treated with propranolol, 24 started treatment prior to 45 weeks CGA. Mean CGA at initiation of treatment was 42 weeks. Sixty-seven percent were female and 75% were white, non-Hispanic. Mean duration of treatment was 255 days. Twenty-two patients (92%) had clear benefit from treatment at a dose of 1-3 mg/kg/day. The most common side effects were sleep disturbance (21%), irritability (17%), and cool hands/feet (13%). There were no serious adverse events. CONCLUSIONS: In this cohort of 24 patients with corrected age <5 weeks (CGA <45 weeks), propranolol was safe and effective for the treatment of infantile hemangiomas. Larger, prospective studies are indicated to investigate propranolol in this age group.

Computed Tomography Scans in Children With Hemophilia After Minor Head Trauma.

OBJECTIVES: Children with hemophilia have the usual childhood risk of falls and head trauma. Head computed tomographies (HCTs) are fast, detailed, and readily available, but increased radiation exposure in the pediatric population is now recognized as causing increased brain malignancy. By examining the incidence of intracranial cerebral hemorrhage in this population, we will be able to weigh risks and benefits of HCT use more accurately. METHODS: Using a retrospective chart review, we examined past medical records of pediatric patients, aged 0 to 15 years, with hemophilia presenting to 1 academic medical center. Primary outcomes included number of head CTs ordered, total and per patient over the years studied, and the incidence of positive findings, as defined by presence of blood products as documented by radiologist final read/interpretation. RESULTS: The mean number of head CTs per child was 2.5 (range, 1-10). None of the HCT scans were read as intracranial cerebral hemorrhage, and none of the patients had findings that lead to neurosurgical intervention. In a sensitivity analysis, applying Pediatric Emergency Care Applied Research Network head injury criteria, 11 HCT scans would be ordered for a reduction of 80 HCTs, or a decrease of 2 HCT scans per child. No incidence of intracranial cerebral hemorrhage would have been missed. CONCLUSIONS: Our findings suggest that in the child with hemophilia and a history of minor head trauma, exposure to the radiation of a HCT based on the diagnosis of hemophilia alone may not be necessary but that imaging decisions need to be made in conjunction with clinical examination findings and neurologic status.

Infantile Hemangioma: A Current Review.

Infantile hemangiomas (IHs) are common vascular lesions which are benign but can cause significant functional and cosmetic morbidity. Since the fortuitous discovery of propranolol being effective to treat IH over a decade ago, the therapy and prognosis for children with IH have improved dramatically. Oral propranolol (as well as other oral beta-blockers and topical timolol) are safe and effective treatments, and have now supplanted other therapies. Making the correct diagnosis is crucial, because other vascular lesions can mimic IH. In addition, IH can be the first manifestation of an underlying syndrome. For IH requiring treatment, initiating treatment early is key to optimizing success. Therefore, early recognition and referral, if necessary, are important. Continued research on IH, both basic science and clinical, should result in continued advances.

COVID-19-Related Reduction in Emergency Health Care Utilization Among Febrile Pediatric Oncology Patients.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic has disrupted normal health care utilization patterns worldwide, including decreasing emergency department (ED) visits for various medical emergencies. We examined whether this pattern was present in febrile pediatric oncology patients. In this single-center cohort study, we conducted a retrospective chart review of ED visits of febrile pediatric oncology patients during the first 4 months of the global SARS-CoV-2 pandemic and compared those data to the same time periods in the previous 2 years. During the first 5 months of the pandemic, 25 pediatric oncology patients with fever visited our ED; 65 children visited during the same time period in 2018; and 60 visited in 2019. Compared with 2018 and 2019, encounters for 2020 were decreased by 62% and 58%, respectively. A significantly higher percentage of febrile pediatric oncology patients (84%) were admitted to our hospital during the pandemic compared the previous years (58%). Of concern is the possibility that fear of exposure to coronavirus disease-19 (COVID-19) at our health care facility prompted caregivers of pediatric oncology patients to avoid seeking care for their child with fever. Consistent communication with families about the life-threatening nature of fever should be prioritized among pediatric oncology providers.

Endoscopic Ultrasound for Diagnosis and Management of Pediatric Gastrointestinal Stromal Tumor.

Gastrointestinal (GI) stromal tumors arise from the interstitial cells of Cajal and are rare in the pediatric population. The most common clinical manifestation is anemia secondary to GI bleeding. Endoscopy is commonly used for diagnostic and therapeutic interventions of an obstructing mass or gastrointestinal bleed, while experience with endoscopic ultrasound (EUS) and EUS fine needle aspiration (EUS-FNA) for pediatric patients with suspected gastric tumors is limited. We report 2 cases, a 14-year-old male and an 11-year-old female, who presented with symptomatic anemia. Both patients were diagnosed with GI stromal tumors of the stomach using EUS and EUS-FNA. This report shows that EUS and EUS-FNA are safe and effective diagnostic tools for pediatric patients.

Eutectic Mixture of Lidocaine and Prilocaine Decreases Movement and Propofol Requirements for Pediatric Lumbar Puncture During Deep Sedation: A Randomized, Placebo-Controlled, Double Blind Trial.

Deep sedation/general anesthesia is commonly used in pediatric oncology patients undergoing lumbar puncture (LP). Propofol is often used for sedation, with or without a narcotic. We hypothesized that eutectic mixture of lidocaine and prilocaine (EMLA) would allow for lower cumulative doses of propofol and less movement. We performed a prospective, randomized, double blind, placebo-controlled trial in children undergoing sedation for LP. Standard initial weight-based doses of propofol and fentanyl were administered, with either EMLA cream or a placebo cream applied topically. The primary outcome was the total dose of propofol administered to each patient. We also tracked patient movement and complications. Twenty-seven patients underwent 152 LPs. Patients randomized to EMLA cream (n=75) were significantly more likely to receive a lower dose of propofol (2.94 mg/kg, SE=0.25, vs. 3.22 mg/kg, SE=0.19; P=0.036) and to not require additional propofol doses (probability 0.49, SE=0.08 vs. 0.69, SE=0.06; P=0.001) compared with patients randomized to placebo cream (n=77). In addition, patients with EMLA cream were significantly less likely to demonstrate minor or major movement. EMLA cream results in less movement and less propofol administration in pediatric oncology patients undergoing sedation for LP.

A conceptual model of fertility concerns among adolescents and young adults with cancer.

OBJECTIVE: For adolescents and young adults (AYAs), cancer-related fertility concerns (FC) are salient, disruptive, and complex. Clinical communication about FC and fertility preservation options are suboptimal, increasing patient distress. The purpose of this study is to construct a conceptual model of FC among AYAs with cancer to inform future measurement development. METHODS: Concept elicitation interviews were conducted with a purposive sample of stakeholders: 36 AYAs (10 adolescents, 12 emerging adults, and 14 young adults), 36 AYA oncology health care providers, and 12 content experts in cancer-related infertility. The constant comparative method was used to identify themes and properties that illustrate AYAs' conceptualization and/or experience of FC. RESULTS: Thirteen themes characterized FC among AYAs with cancer, varying by stakeholder group and domain affiliations. Themes were grouped by four domains (e.g., affective, information, coping, and logistical), which organized the conceptual model. Affective experiences were further determined to be an important component within the other three domains. AYAs' fertility and fertility preservation experiences were shaped by communication factors and timing factors including placement along the lifespan/cancer continuum. CONCLUSIONS: AYA FC are characterized by uncertainty and confusion that may contribute to future decisional regret or magnify feelings of loss. Results add to previous research by examining individual, relational, and health care factors that fluctuate to inform fertility preservation perceptions and decision-making across the AYA age spectrum. Findings will be used to develop and test new self-report measures of FC among AYAs with cancer and survivors using classic and modern measurement theory approaches.

Nontranfusional Management of Severe Anemia in an Adolescent Jehovah's Witness Patient.

Severe anemia in Jehovah's Witness patients has long been a complex and sometimes divisive issue, especially in children and adolescents. In adolescent patients old enough to express their wishes, the decision to transfuse becomes more complicated. We present the case of a 12-year-old Jehovah's Witness female with severe anemia (hemoglobin of 2.6 g/dL) secondary to menorrhagia. She was successfully managed without transfusion, for which the patient and her family were deeply grateful. This case demonstrates that it is possible to manage severe iron deficiency anemia without transfusion.

Fertility preservation for pediatric male cancer patients: illustrating contemporary and future options; a case report.

The main aim of current pediatric male fertility preservation programs is storing spermatogonia stem cell (SSC) prior to starting cancer treatment. From July 1st, 2014 to May 1st, 2020; 170 patients have been recruited in Wake Forest Testicular Tissue Banking Program. The existence of multiple testis biopsies in different time points and detailed histological analyses of a unique cancer patient, provided an educational opportunity to investigate testis condition in different phases of cancer management. A pediatric male cancer patient with B-cell acute lymphoblastic leukemia (ALL) had multiple testicular leukemia recurrences and went through several testicular biopsies, to identify leukemic infiltration as well as considering fertility preservation. Infiltration of leukemia cells into both testes was identified. Neither elongated spermatid nor sperm were detected, but germ cells including SSC, spermatocyte and round spermatid could be identified in the stored tissue even after initial cancer treatment. Different germ cells were identified by hematoxylin and eosin (H&E) staining and specific immunohistochemical (IHC) markers including PGP9.5/UCHL1 or MAGE-A4 (spermatogonia), SYCP3 (spermatocyte) and PRM1 (round spermatid). This emphasizes the importance of offering testicular biopsy to pediatric cancer patients at risk of infertility regardless to the stage of cancer treatment, although earlier biopsy is preferred. Promising research on in vitro spermatogenesis and auto-transplantation support the practice of SSC preservation. In addition, finding and storing round spermatids isolated from testicular biopsy provides a currently available option of round spermatid injection (ROSI). Given the complexity of managing cancer while considering fertility preservation, a multidisciplinary collaboration is important to achieve optimal overall outcomes.

Adaptive and maladaptive forms of disengagement coping in caregivers of children with chronic illnesses.

Caregivers of children with chronic illnesses experience elevated stress and reduced self-care. Although self-care can be beneficial, it is a form of disengagement coping, disengaging from the stressor to try and feel better, which has been characterized as a maladaptive coping strategy. In this study, we test the formulation that avoidance, avoiding the stressor and any thoughts related to it, is a maladaptive disengagement coping strategy, whereas distraction, taking a break from the stressor to do something pleasant, is an adaptive disengagement coping strategy. We assessed these strategies as well as psychosocial outcomes and trait predictors in caregivers of children with chronic illnesses. Results showed that those high in avoidance coping reported lower well-being, higher depression and higher stress. Alternatively, when controlling for avoidance, those high in distraction reported higher well-being, lower depression and lower stress. In addition, distraction exhibited strong relationships to increased positive emotions during caregiving situations and was associated with positive personality traits. These results suggest that not all disengagement coping strategies are equal; although avoidance may be a maladaptive strategy, distraction can be an effective positive emotional strategy for coping with the chronic stress of caregiving for a child with a chronic illness.

Thoracic duct embolization in kaposiform lymphangiomatosis.

An 11-year-old girl with kaposiform lymphangiomatosis presented with recurrent chylous pericardial effusions that were refractory to pericardial drainage and medical therapy. Magnetic resonance imaging demonstrated a prominent lymphatic duct with anterior mediastinal extension into the left clavicular region and a region of high signal that was favored to represent a low-flow lymphatic malformation. The patient underwent direct access thoracic duct lymphangiography with thoracic duct embolization and sclerotherapy of the large left-sided neck and pericardial lymphatic malformation. After the procedure, her pericardial effusions resolved, and she has remained asymptomatic for 15 months.

Risk factors for chemotherapy-induced nausea in pediatric patients receiving highly emetogenic chemotherapy.

BACKGROUND: Little is known regarding risk factors for chemotherapy-induced nausea (CIN) in pediatric patients. PROCEDURE: A secondary analysis was conducted of a previously published multicenter, prospective, randomized, single-blind, sham-controlled trial assessing the efficacy of acupressure in preventing CIN in pediatric patients receiving highly emetogenic chemotherapy. The primary outcome was nausea severity, self-reported using the Pediatric Nausea Assessment Tool. The relationships between acute and delayed nausea severity and patient- (sex, race, age, and cancer diagnosis) and treatment-related (chemotherapy, antiemetic prophylaxis, CIN, and vomiting control) factors were analyzed by a proportional odds generalized estimating equation approach. The acute phase started with administration of the first and continued for 24 hours after the last chemotherapy dose. The delayed phase started at the end of the acute phase and continued until the next chemotherapy block (maximum seven days). RESULTS: In the acute and delayed phases, 165 and 144 patients provided data for analysis, respectively. Nonwhite race was significantly associated with higher acute phase nausea severity (OR, 1.7; 95% CI, 1.1-2.6). Poor CIN control in the acute phase (OR, 16; 95% CI, 4.0-64.6), diagnosis of a cancer other than a central nervous system (CNS) tumor (OR, 2.5; 95% CI, 1.2-5.3), and cisplatin administration (OR, 3.7; 95% CI, 2.1-6.0) were significantly associated with higher delayed phase nausea severity. CONCLUSION: Acute phase CIN was associated with nonwhite race. Delayed phase CIN was associated with poor acute phase CIN control, diagnosis of non-CNS cancer, and receipt of cisplatin. These findings will inform future antiemetic trial design.

Sudden Cardiac Arrest Due to Hemophagocytic Lymphohistiocytosis in a Child.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon hyperinflammatory condition in children that may acutely mimic septic shock. Sudden out-of-hospital cardiac arrest in children is also uncommon and may be of unclear etiology upon initial presentation. CASE REPORT: A 10-year-old previously healthy child presented with sudden cardiac arrest after an insidious course of throat pain, fever, and progressive altered mental status. He was subsequently diagnosed with Epstein-Barr virus-associated HLH and suffered cerebral edema and death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: HLH has not previously been described as a cause of sudden out-of-hospital cardiac arrest in children. Rapid diagnosis of underlying cause of an unexpected cardiac arrest may help guide appropriate therapy to salvage organ function.

Pneumocystis Jirovecii Pneumonia During Sirolimus Therapy for Kaposiform Hemangioendothelioma.

Sirolimus is an effective therapy for children with kaposiform hemangioendothelioma with or without the Kasabach-Merritt phenomenon. We report the case of a child with kaposiform hemangioendothelioma and the Kasabach-Merritt phenomenon who developed Pneumocystis carinii pneumonia (PCP) while on sirolimus and a prednisolone taper, after lack of adequate response to prednisolone, propranolol, and vincristine. He had a prompt positive clinical and laboratory response to sirolimus, but 4 weeks after starting it, at the age of 4 months, he developed PCP. This led to respiratory failure, which required extracorporeal membrane oxygenation. Sirolimus was temporarily discontinued, and he was successfully treated for PCP with sulfamethoxazole-trimethoprim and methylprednisolone. He was restarted on sirolimus 3 weeks after discharge and given sulfamethoxazole-trimethoprim prophylaxis. At the age of 22 months, while still on sirolimus, the lesion continued to improve with test results revealing stable hemoglobin and platelet counts. PCP is a rare but life-threatening side effect of sirolimus therapy, especially in the setting of concurrent steroid treatment. Pneumocystis prophylaxis should be considered for patients receiving sirolimus.