Pediatric moderate aplastic anemia (MAA) lacks defined diagnostic criteria and a clear standard-of-care due to the limited knowledge of its pathophysiology and natural history. The approach to MAA has been historically inconsistent as the proposed survey demonstrates. To understand current diagnostic and management practices for patients with MAA, a survey was conducted among members of the North American Pediatric Aplastic Anemia Consortium (NAPAAC), including 104 providers across 57 institutions. The survey demonstrates broad variability regarding the working definition, diagnostic work-up, and therapeutic management of children with MAA. The diagnostic work-up and treatment options for children with MAA are largely driven by management guidelines for pediatric severe aplastic anemia (SAA). Treatment triggers, type of therapy, and outcomes varied widely among respondents. Curated next generation sequencing panels and whole exome/whole genome sequencing were included by only 55% and 9% of respondents, respectively which suggests the need to more broadly consider inherited bone marrow failure syndromes in the differential diagnosis for these patients. Effective and risk-adapted treatment for MAA requires a better understanding of the biology, natural history, and treatment outcomes for this heterogeneous population.

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 2005-2020 with > 6 months 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 2 patients were deceased (1.3%). Over 60% (n=96) demonstrated treatment response at 3 months and >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=0.03) but there was 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 were 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.

Congenital lymphatic leak may develop in patients with maldeveloped lymphatics and result in life-threatening fluid and electrolyte imbalance, protein deficiency and immunodeficiency. Rapid diagnosis and therapy are necessary to prevent these complications; however, the field lacks clinical trials to support standardized diagnostic treatment guidelines. We present our current multidisciplinary approach to the diagnosis and management of congenital lymphatic leak including chylous pleural effusion and ascites. Depending on the rate of lymphatic leak, therapy can range from observation with nutritional modifications to surgical and interventional procedures aimed to reduce lymphatic drainage. Modalities to image central and peripheral lymphatics have advanced considerably. Genetic variants and subsequent targets that drive lymphatic maldevelopment have expanded the repertoire of possible pharmacotherapeutic options.