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Background Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, is often mistaken for a congenital pulmonary airway malformation, as the two entities can be difficult to distinguish on imaging and pathology. Diagnosis of PPB should prompt workup for DICER1 syndrome, an autosomal dominant tumor predisposition syndrome. We report a newborn with a congenital PPB presenting with tachypnea and hypoxia, who was found to have variant of uncertain clinical significance (VUS) in DICER1. Case presentation A term female infant developed respiratory distress shortly after birth. Initial imaging was concerning for a congenital pulmonary airway malformation versus congenital diaphragmatic hernia, and she was transferred to a quaternary neonatal intensive care unit for management and workup. Chest CT angiography demonstrated a macrocytic multicystic lesion within the right lower lobe without systemic arterial supply. The pediatric surgery team was consulted, and the neonate underwent right lower lobectomy. Pathology revealed a type I PPB. Oncology and genetics consultants recommended observation without chemotherapy and single gene sequencing of DICER1, which identified a germline VUS in DICER1 predicted to alter splicing. RNA-sequencing from blood demonstrated that the variant resulted in an in-frame deletion of 29 amino acids in a majority of transcripts from the affected allele. Due to the patient’s young age at presentation and high clinical suspicion for DICER1 syndrome, tumor surveillance was initiated. Renal and pelvic ultrasonography were unremarkable. Conclusion We present the case of a term neonate with respiratory distress and cystic lung mass, found to have a type I PPB with a germline VUS in DICER1 that likely increased her risk of DICER1-related tumors. Nearly 70% of patients with PPB demonstrate germline mutations in DICER1. Review of RNA sequencing data demonstrates the difficulty in classifying splice variants such as this. Penetrance is low, and many patients with pathogenic DICER1 variants do not develop a malignancy. Best practice surgical and oncologic recommendations include an individualized approach and tumor board discussion. This case highlights the importance of a multidisciplinary team approach and the utility of international registries for patients with rare diagnoses.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable clinical responses in hematologic malignancies. Recent advances in CAR T-cell therapy have expanded its application into other populations including older patients and those with central nervous system and solid tumors. Although its clinical efficacy has been excellent for some malignancies, CAR T-cell therapy is associated with severe and even life-threatening immune-mediated toxicities, including cytokine release syndrome and neurotoxicity. There is a strong body of scientific evidence highlighting the connection between immune activation and neurocognitive and psychological phenomena. To date, there has been limited investigation into this relationship in the context of immunotherapy. In this review, we present a biobehavioral framework to inform current and future cellular therapy research and contribute to improving the multidimensional outcomes of patients receiving CAR T-cell therapy.

Inflammatory physiology has been linked to behavioral and emotional symptoms in a variety of contexts and experimental paradigms. Hematopoietic cell transplantation (HCT) represents an intersection of significant immune dysregulation and psychosocial stress, and this biobehavioral relationship can influence important clinical outcomes. For those undergoing HCT with inflammation-related neuropsychiatric symptoms, using targeted agents such as the IL-6 receptor antagonist tocilizumab may be an effective therapeutic approach. We conducted an observational cohort study to explore patient reported outcomes (PROs) and inflammatory biomarkers among allogeneic HCT recipients who received tocilizumab compared to those who did not. Individuals on a larger trial of tocilizumab for prevention of graft-versus-host disease received a single dose of tocilizumab 24 h prior to stem cell infusion. Measures of anxiety, depression, pain, fatigue, and sleep quality and parallel blood samples for inflammatory cytokines were collected from participants and an analogous comparison cohort at baseline and Day 28 after stem cell infusion. Demographic and medical characteristics were reported; an analysis of covariance regression model was fitted to evaluate differences in PROs and distance correlation t-tests assessed for associations between biomarkers and PRO measures. For n = 18 tocilizumab-treated and n = 22 comparison patients, there were no significant differences between patient demographics, but the tocilizumab cohort had a different distribution of primary diagnoses (p = 0.009) with more patients with leukemias and a higher proportion of patients in their first remission (64% vs 28%, p = 0.024). Depression was higher at Day 28 compared to baseline in both groups (comparison group: +5.1 [95% CI 0.14-10, p = 0.045], tocilizumab: +8.6 [95% CI 2.3-15, p = 0.011]), though the difference between groups did not reach statistical significance. The tocilizumab group had significantly increased circulating IL-6 and decreased CRP at Day 28 (all p 0.05). There was an association between collective baseline biomarkers and PROs (distance correlation dCor = 0.110, p = 0.005), but this same association was not present at Day 28 (dCor = -0.001, p = 0.5). In univariate analyses, a 10-fold increase in plasma IL-6 was associated with a 3.6-point higher depression score (95% CI 1.0-6.2, p = 0.008). In this exploratory analysis of PROs and inflammatory biomarkers in patients undergoing HCT, tocilizumab was not associated with favorable patient-reported symptom profiles. This finding is aligned with our prior work in the HCT population but diverges from hypothesized therapeutic effects of tocilizumab on depressive symptoms, thus highlighting the need for larger prospective translational studies in biobehavioral HCT research.

A previously healthy 8-month-old female infant presenting with lethargy and bilateral eye redness and cloudiness had bilateral hypopyon uveitis, which persisted despite topical steroids. Cytology of the anterior chamber and cerebrospinal fluid and flow cytometry of cerebrospinal fluid revealed malignant cells consistent with acute monocytic leukemia. Bone marrow aspirates and biopsies showed no evidence of disease. She was treated with systemic and intrathecal chemotherapy, with subsequent remission and resolution of pseudo-hypopyon. Anterior chamber involvement is a rare presentation of acute myeloid leukemia and may indicate concurrent central nervous system involvement. This has important therapeutic implications, because additional treatment modalities such as intrathecal chemotherapy, local chemotherapy, and ocular radiation may be required to overcome the “pharmacologic sanctuary” created by the blood–ocular barrier. [ J Pediatr Ophthalmol Strabismus . 2021;58(5):e30–e33.]

10029 Background: Parents of children with cancer experience significant levels of distress, which may negatively impact surviving patients and family members. Positive psychology interventions have shown promise, but few address the well-being of parents. The objective of this study was to test the efficacy of a resilience intervention, Promoting Resilience in Stress Management-Parent (PRISM-P), among parents of children with cancer. Methods: This study was a phase 2, 1:1:1 RCT. Eligible participants were English-speaking parents of children 2-24 years-old receiving cancer-directed therapy at Seattle Children’s Hospital. PRISM-P is a skills-based program targeting resilience resources. Parents were randomized to usual care (UC), UC plus individual PRISM-P (1:1), or UC plus group PRISM-P (group). Parents completed surveys at baseline and 3 months measuring resilience (primary outcome, 10-item Connor Davidson Resilience Scale (CDRISC)) and other secondary outcomes including stress, social support, and benefit-finding. We performed an intention-to-treat analysis using unadjusted linear mixed-effects modeling to estimate PRISM effects on score change. With n = 25 per arm, we achieved 80% power to detect an effect size (CDRISC change) of 5.1 (Cohen’s d = 0.8) with a type 1 error rate of 0.05. Results: 107 parents enrolled. Of these, 94 (88%) completed baseline surveys and 77 (72%) completed 3 month surveys. Mean (SD) resilience score change in UC, 1:1 and group arms was -2 (3.5), 1 (5.3) and -1 (5.0), respectively. In mixed models, the estimated 1:1 PRISM benefit for resilience score change vs. UC was +2.8 (95% CI: 0.5,5.2, p = 0.02) while there was no evidence of a group benefit (beta 0.4, 95% CI: -2.1, 2.8, p = 0.76.). Models for secondary outcome score change found a PRISM advantage for benefit finding, where the 1:1 vs. UC difference was +0.5 (95% CI: 0.2, 0.8, p < 0.01) and the group vs. UC difference was +0.4 (0.0, 0.7, p = 0.05). Conclusions: Compared to UC, 1:1 PRISM-P was associated with improved resilience change, and both PRISM-P intervention arms were associated with greater benefit-finding. Future studies will explore larger scale efficacy and alternative delivery design. Clinical trial information: NCT02998086.

Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCA) are ubiquitous environmental contaminants which have been regarded as risk factors for congenital heart malformations. An increasing body of evidence from in vivo and in vitro studies supports the notion that exposure to TCE and TCA may interfere with normal embryonic heart development. The expression of several genes coding for factors implicated in the regulation of cardiac development has been shown to be modified by TCE or TCA, but the molecular mechanisms that mediate these effects are still obscure. In this study, we investigated the global changes in gene expression caused by exposure of P19 embryonal carcinoma cells to TCE and TCA, and whether or not TCE and/or TCA influence the expression levels of genes encoding for proteins that regulate calcium fluxes in cardiac cells. We report that TCE and TCA disrupt the expression of genes involved in processes important during embryonic development suggesting that exposure to environmentally significant concentrations of TCE may have deleterious effects on specific stages of cardiac differentiation.