Investigating the correlation between small molecular inhibitor utilization, peripheral blood monocytes, and treatment outcomes in Rosai Dorfman disease

Reynolds, Samuel B.; Wilcox, Sabrina; Li, Qing; Ahmed, Asra Z.

doi:10.1007/s00277-023-05494-x

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…We wish to acknowledge even these negative findings as the trends are relevant and are expected to reach significance in ongoing analyses within our cohort. This is further supported by similar findings seen within histiocytic diseases in 2023 studies by Razanmahery et al and Reynolds et al [28,29]. While these trends remain under expansive investigation, the aforementioned studies and cumulative clinical data now serve as the basis for ECD management as set forth by the guidelines from the National Comprehensive Cancer Network [30].…”

Section: Discussionmentioning

confidence: 55%

“…Prior examinations into histiocyte ontogeny would support this theory. Specifically, research has suggested that histiocytic disorders arise from pre-existing clonal hematopoiesis whereby clonal hematopoietic progenitors harboring TET2 mutations later differentiate into circulating monocytes that acquire BRAF mutations and circulate as ECD [25][26][27][28][29]. With this theory, relative peripheral monocytosis at time of progression, followed by reduction while on therapy, might be reflective of patients' ECD responding to therapy.…”

Section: Discussionmentioning

confidence: 99%

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Erdheim–Chester Disease: Investigating the Correlation between Targeted Treatment Therapy and Disease Outcomes

Wilcox,

Reynolds,

Ahmed

2024

Cancers

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A retrospective analysis of 20 adult patients with histopathological and clinical diagnoses of ECD was conducted at a single institution over a twenty-year period (2002–2022). Clinical responses were compared on the basis of treatments rendered, which included chemotherapy, immunotherapy, systemic corticosteroids, surgery and radiation, or targeted agents, referring to any small molecular inhibitors. Treatment response evaluation varied by the anatomic site(s) of disease, the extent of disease at diagnosis, and the imaging modality employed. In this analysis, patients were treated with a combination of targeted agents, myelosuppressive therapies, and radiation at various points in their disease courses. Of these, the most common treatment modality rendered was targeted therapy, employed in 11 of 20 patients. Partial responses or better were observed in 15 of 20 patients. Rates of stable disease trended towards being more frequent with targeted therapy versus conventional therapy but did not reach significance (p = 0.2967). Complete response rates trended towards being more common with conventional therapy than molecular (p = 0.5) but were equivocal overall. Trends of peripheral blood absolute monocytes with relation to disease activity were reviewed as recent literature implied that monocyte levels surrounding disease progression were of potential prognostic significance in histiocytic diseases. Amongst the patients who progressed at any point during their treatment course, absolute monocyte count (in K/µL) was identified at the closest available timepoint prior to or following disease progression and at the lowest value (nadir) following re-institution of therapy prior to any additional agent(s) being employed. There was no statistically significant difference in either of these monocyte values nor in disease outcomes with respect to treatments rendered within our cohort. However, our cohort consists of a heterogenous population of patients with ECD with data that highlights several trends over a longitudinal period, spanning the advent of targeted therapy. Significant differences are anticipated in ongoing analyses.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Erdheim–Chester Disease: Investigating the Correlation between Targeted Treatment Therapy and Disease Outcomes

Wilcox,

Reynolds,

Ahmed

2024

Cancers

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“…While the present treatment paradigms for both diagnostic and management strategies are well established, information on trends in biomarkers and even basic laboratory data are lacking in the available literature, prompting the forthcoming investigation into the signi cance of peripheral monocytosis in LCH, especially in adults with single system pulmonary LCH [4,5].…”

Section: Introductionmentioning

confidence: 99%

Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis

Ali,

Reynolds,

Wilcox

et al. 2024

Preprint

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We aimed to examine the association between relative monocytosis and the recurrence of pulmonary Langerhans Cell Histiocytosis. Clinical, laboratory, radiographic and treatment data for 86 patients with a histopathological diagnosis of Langerhans Cell Histiocytosis over a 20-year duration. Parameters such as biological sex, age at diagnosis, time to diagnosis, molecular diagnostic data and imaging were collected. Treatment responses were assessed predominantly through radiography, with RECIST 1.1 criteria applied to MRI or CT scans and PERCIST utilized for serial PET imaging. Investigators also assessed peripheral blood absolute monocyte count at various time points, including initial diagnosis and the most recently available value. While peripheral blood absolute monocyte count between the earliest assessed timepoint and latest value did not differ, the mean value on progression (0.94 K/µL), however, was significantly higher than that following re-institution of therapy (0.31, p = 0.000794. Our observation of relative monocytosis on LCH disease progression may be related to an increase in circulating LCH on disease progression or from increased monocyte production for later differentiation into mature dendritic cells that participate in MHC Class 1 upregulation. This trend is especially evident in pulmonary LCH which is incited by tissue trauma and irritation by environmental factors. The phenomena observed in our study parallel other non-LCH cohorts, specifically in 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, expanded integrated genomic-transcriptomic sequencing analyses to evaluate the molecular character of LCH and ultimately clarify the origin of this monocyte trend are in progress. These studies are poised to offer invaluable insight to the molecular mechanisms underlying LCH, specifically as they pertain to monocyte signaling and differentiation.

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Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis

Ali,

Reynolds,

Wilcox

et al. 2024

Ann Hematol

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Investigating the correlation between small molecular inhibitor utilization, peripheral blood monocytes, and treatment outcomes in Rosai Dorfman disease

Cited by 4 publications

References 14 publications

Erdheim–Chester Disease: Investigating the Correlation between Targeted Treatment Therapy and Disease Outcomes

Erdheim–Chester Disease: Investigating the Correlation between Targeted Treatment Therapy and Disease Outcomes

Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis

Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis

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