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.

How we approach localized vascular anomalies.

Vascular anomalies are a group of disorders divided into two distinct subtypes: vascular tumors and vascular malformations. Vascular tumors are proliferative in nature, while malformations are nonproliferative. Simple, localized vascular malformations refer to a group of malformations that are localized to a single area of involvement. These simple malformations include capillary, lymphatic, venous, and arteriovenous malformations. The pediatric hematologists and oncologists are becoming increasingly involved in the diagnosis and management of these disorders. This review presents four cases as a means to discuss the diagnosis, clinical and imaging features, and management strategies of simple, localized vascular malformations.

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.

Coagulation Abnormalities and Clinical Complications in Children With SARS-CoV-2: A Systematic Review of 48,322 Patients.

Given the limited information on the coagulation abnormalities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pediatric patients, we designed a systematic review to evaluate this topic. A comprehensive literature search was conducted for "SARS-CoV-2," "coagulopathy," and "pediatrics." Two authors independently screened the articles that the search returned for bleeding, thrombosis, anticoagulant and/or antiplatelet usage, and abnormal laboratory markers in pediatric patients with SARS-CoV-2, and the authors then extracted the relevant data. One hundred twenty-six publications were included. Thirty-four (27%) studies reported thrombotic complications in 504 patients. Thirty-one (25%) studies reported bleeding complications in 410 patients. Ninety-eight (78%) studies reported abnormal laboratory values in 6580 patients. Finally, 56 (44%) studies reported anticoagulant and/or antiplatelet usage in 3124 patients. The variety of laboratory abnormalities and coagulation complications associated with SARS-CoV-2 presented in this review highlights the complexity and variability of the disease presentation in infants and children.

Applicability of the Curaçao Criteria for the Diagnosis of Hereditary Hemorrhagic Telangiectasia in the Pediatric Population.

OBJECTIVE: To evaluate the accuracy of the clinical Curaçao criteria in the diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and adolescents. STUDY DESIGN: This was a retrospective, multicenter chart review of 673 patients evaluated between 2002 and 2016; 290 were eligible for the study. Genetic testing for a pathogenic mutation was considered the gold standard against which the clinical Curaçao criteria were compared. Patients were divided into 4 age categories: 0-5, 6-10, 11-15, and 16-21-years. Sensitivity and specificity were calculated for each age group, and for the overall population. RESULTS: Overall the Curaçao criteria had a sensitivity of 68% (95% CI 60%-76%) and a specificity of 98% (95% CI 91%-100%). Sensitivity was lowest in the 0- to 5-year group, and increased with advancing age. The Curaçao criteria had the highest sensitivity in the 16- to 21-year-olds. Specificity was 100% in all age groups except for the 11- to 15-year-olds. CONCLUSIONS: This study evaluated the use of the Curaçao criteria for the diagnosis of HHT in the pediatric population with a family history of HHT. In those between the age of 0 and 21 years who meet 1 criterion (unlikely HHT) or 2 criteria (possible HHT), genetic testing is preferred for diagnosis. The Curaçao criteria appear to reliably diagnose HHT in children and adolescents who meet 3 or 4 criteria (definite HHT).

Inconsistency in classifying vascular anomalies: What's in a name?

BACKGROUND: Vascular anomalies are a heterogeneous group of disorders seen in children and adults. A standard nomenclature for classification has been offered by the International Society for the Study of Vascular Anomalies. Its application is important for communication among the multiple specialties involved in the care of patients and for planning treatment, as well as for research and billing. We hypothesized that terminology still is not uniformly applied, and that this could have an impact on treatment. METHODS: We retrospectively reviewed the medical records of patients with nonbrain lesions from our institutional vascular anomalies database seen during 2010-2016 for whom at least one clinic visit, radiologic imaging report, and pathology report were available to compare diagnoses among and within disciplines, and treatment recommendations. Diagnoses and referral patterns by community healthcare providers were also reviewed. RESULTS: Of 400 patients seen during the targeted time interval, 35 had clinical, imaging, and pathology reports. Agreement in terminology from initial clinic notes with imaging and pathology reports was noted in only three cases (9%). "Hemangioma" was often misused; "lymphangioma" and "cystic hygroma" persist as diagnostic labels. Community healthcare providers referred vascular malformations with a diagnosis of "mass" or "hemangioma" in 17 of 18 cases where that information was available. Incomplete or mislabeling of vascular anomalies sometimes delayed referrals to appropriate clinics, though it did not have a major impact on treatment. CONCLUSIONS: An understanding of vascular anomalies as tumors or malformations is not uniform. Ongoing education will be needed to promote consensus terminology and facilitate referrals.

RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis. PROCEDURE: We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis. RESULTS: We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01). CONCLUSIONS: RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.

Thrombosis in infants in the neonatal intensive care unit: Analysis of a large national database.

BACKGROUND: Thrombosis in the neonatal population is rare, but increasing. Its incidence and management are not well understood. OBJECTIVES: To investigate the incidence, associated factors, and management of thrombosis in the neonatal intensive care unit (NICU) population. PATIENTS/METHODS: We performed a retrospective cohort study of infants admitted to a Pediatrix Medical Group-affiliated NICU from 1997 through 2015. We determined the prevalence of venous and arterial thrombosis, and assessed demographic characteristics and known risk factors. Categorical variables were compared with the Pearson χ2 test and continuous variables with Wilcoxon rank-sum tests. Stepwise logistic regression was used to identify associated factors. The primary outcome was incidence of thrombosis. Secondary analyses investigated correlations between clinical and demographic characteristics and thrombosis. RESULTS: Among 1 158 755 infants, we identified 2367 (0.20%) diagnosed with thrombosis. In a multivariable regression analysis, prematurity, male sex, congenital heart disease, sepsis, ventilator support, vasopressor receipt, central venous catheter, invasive procedures, and receipt of erythropoietin were associated with increased risk of thrombosis, while Black race and Hispanic ethnicity were associated with reduced risk. The majority of infants diagnosed with thrombosis (73%) received no anticoagulation, but anticoagulant use in infants with thrombosis was higher than those without (27% versus 0.2%, P < .001). Thrombosis in infants was associated with higher mortality (11% versus 2%, P < .001) and longer hospital stays (57 days, [interquartile range (IQR) 28--100] versus 10 days, [IQR 6--22], P < .001). CONCLUSIONS: In the largest national study to date, we found that thrombosis in NICU patients is associated with prematurity, low birth weight, sepsis, and invasive procedures.