Abstract 2564: Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans cell histiocytosis
Authors: Haadi Ali, Sam Reynolds, Sabrina Wilcox, Naina Chipalkatti, Asra Ahmed
Journal: Cancer Research (2024)

Abstract Introduction: Langerhans Cell Histiocytosis (LCH) is a rare disorder characterized by clonal hematopoietic cell expansion forming eosinophilic granulomas. Treatment approaches vary based on disease severity. Despite established therapies, assessing treatment response, particularly regarding peripheral blood monocytes, lacks comprehensive markers. Methods: We studied 76 LCH patients, collecting data on demographics, diagnostic methods, and treatment responses. Peripheral blood absolute monocyte counts were analyzed at key time points, including disease onset, progression, and post-therapy reinstatement, using statistical tests for comparison. Results: Analyzing data from 76 patients (average age: 38), we found diverse disease presentations, with common imaging modalities being CT (37), PET (29), and MRI (22). Complete responses were observed in 17 of 49 patients, with 11 undergoing local therapy. Conversely, 5 patients with pulmonary LCH and chronic tobacco use showed persistent progression. Notably, peripheral blood monocyte counts did not differ between initial and latest assessments, but on disease progression, the mean count (0.94 K/µL) significantly exceeded that following therapy reinstatement (0.31, p=0.000794). Results: Analyzing data from 76 patients (average age: 38), we found diverse disease presentations, with common imaging modalities being CT (37), PET (29), and MRI (22). Complete responses were observed in 17 of 49 patients, with 11 undergoing local therapy. Conversely, 5 patients with pulmonary LCH and chronic tobacco use showed persistent progression. Notably, peripheral blood monocyte counts did not differ between initial and latest assessments, but on disease progression, the mean count (0.94 K/µL) significantly exceeded that following therapy reinstatement (0.31, p=0.000794). Discussion: LCH is proposed to result from dysregulated hematopoiesis, leading to sequential somatic mutations during monocyte differentiation leading to clonal expansion of CD1A and CD207+ histiocytes. Our finding of increased monocyte count during disease progression may suggest elevated circulating LCH or heightened monocyte production for subsequent differentiation, potentially contributing to MHC Class 1 upregulation. This phenomena mirrors published findings from our own group in patients with Rosai Dorfman and Erdheim Chester Disease. To further elucidate the molecular underpinnings of LCH and explore the etiology of this monocyte trend, genetic sequencing analysis is in progress. Ultimately, monitoring peripheral blood monocyte dynamics could offer valuable insights into LCH progression and treatment response. Citation Format: Haadi Ali, Sam Reynolds, Sabrina Wilcox, Naina Chipalkatti, Asra Ahmed. Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans cell histiocytosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2564.