Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia.

BACKGROUND: Black and Hispanic children with B-acute lymphoblastic leukemia (B-ALL) experience worse outcomes compared with their non-Hispanic white (NHW) counterparts. Immune-based approaches have begun to transform the therapeutic landscape in children with B-ALL. Recent studies identified several alterations in both innate and adaptive immune cells in children with B-ALL that may impact disease risk and outcome. However, the impact of racial/ethnic background on immune microenvironment is less studied, as children of minorities background have to date been severely under-represented in such studies. METHODS: We performed high-dimensional analysis of bone marrow from 85 children with newly diagnosed B-ALL (Hispanic=29, black=18, NHW=38) using mass cytometry with 40 and 38-marker panels. RESULTS: Race/ethnicity-associated differences were most prominent in the innate immune compartment. Hispanic patients had significantly increased proportion of distinct mature CD57 +T-bet+DR+ NK cells compared with other cohorts. These differences were most apparent within standard risk (SR) patients with Hispanic SR patients having greater numbers of CD57 +NK cells compared with other cohorts (43% vs 26% p=0.0049). Hispanic and Black children also had distinct alterations in myeloid cells, with a significant increase in a population of non-classical activated HLA-DR +CD16+myeloid cells, previously implicated in disease progression, compared with NHW counterparts. Racial background also correlated with altered expression of inhibitory checkpoint PD-L1 on myeloid cells. CONCLUSION: There are surprisingly substantial race/ethnicity-based differences in innate immune cells of children with newly diagnosed B-ALL. These differences urge the need to enhance accrual of children from minorities background in immunetherapy trials and may impact their outcome following such therapy.

Head and Neck Langerhans Cell Histiocytosis in Children.

PURPOSE: Controversy exists among head and neck surgical specialties regarding management of Langerhan's Cell Histiocytosis (LCH). The purpose of this study was to evaluate diagnosis, management, and treatment outcomes in children with LCH of the head and neck. METHODS: This is a retrospective cohort study of children with LCH of the head and neck who presented to Children's Healthcare of Atlanta hospital from 2009 to 2021. The independent variables were demographic information, lesion locations, clinical presentation, radiographic findings, diagnostic workup, treatment, and length of follow-up. The patients were grouped based on these variables. The outcome variable was disease reactivation. Descriptive statistics were calculated. RESULTS: There were 3 presentations of LCH of the head and neck. Group 1 presented as a lesion in 1 system without CNS risk (SS-). There were 24 patients with an average age of 10 years. Lesions were located in calvaria and/or mandible. Majority of the patients were treated with only debridement. Two of the patients experienced reactivation. Group 2 presented as a lesion in 1 system with CNS risk (SS+). There were 30 patients with an average age of 6 years. Common locations were temporal bone and/or orbit. These patients present with recurrent ear infections and ptosis. Majority of the patients were treated with chemotherapy (n = 28). One patient had disease reactivation. Group 3 presented with multisystem involvement. There were 13 patients with an average age of 2 years. LCH was found in skin and the lymphatic system. Imaging demonstrated extracranial organ involvement. All of them were treated with chemotherapy. There was 40% reactivation of LCH. CONCLUSIONS: Treatment of LCH depends on presentation. SS- subgroup can be adequately treated via surgical debridement. SS+ and multisystem groups benefit from an early disease diagnosis and require chemotherapy.