Ryu, Jay H.

7050 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm manifesting as unifocal, multifocal, multisystem (MS) or pulmonary LCH (smoking-related). In pediatric LCH, somatic BRAFV600E prevalence is reported at 55-70%, and associated with increased risk of multisystem disease and early treatment failure. Our aim was to describe the prevalence of BRAFV600E mutation and evaluate its association with clinical manifestations and outcomes in adults with LCH. Methods: A retrospective review of adult patients diagnosed with LCH consecutively seen at Mayo Clinic from 2011 to 2020 was performed.Evaluation of association of BRAFV600E mutational status and clinical factors was conducted by the Chi-square test for independence. Progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan Meier method and compared with the log-rank test to assess the effect of BRAFV600E. Results: Of the total LCH cohort ( n= 128), 88 patients with available BRAFV600E results were included in the study. Median age at diagnosis was 41y (range 19 - 88); 52.3% were male. 40 (45.5%) patients had a BRAFV600E mutation. Increasing age was associated with BRAFV600E (10-year increase OR 1.42, 95%CI 1.07-1.89; p= 0.017). No correlation was observed between BRAFV600E status and site of disease, risk organ (RO: liver, spleen, marrow) involvement, or MS disease. Patients with BRAFV600E were 4 times more likely to receive targeted therapy ( BRAF inhibitor) than non- BRAFV600E patients ( p= 0.018). After a median follow up of 46 mo (95% CI 30.8-61.2), PFS was similar between BRAFV600E and non- BRAFV600E patients ( p= 0.167). However, patients with BRAFV600E had a worse 3-year OS compared with non- BRAFV600E patients (84% vs. 97.1%, p= 0.027). Patients who died had a significantly higher age at LCH diagnosis (median 62 vs. 38 years; p= 0.0002). Conclusions: In our cohort of adults with LCH, BRAFV600E was less frequent than reported in pediatric literature and was associated with worse OS. The frequency of BRAFV600E was positively correlated with increasing age. Contrary to reports in pediatric LCH, there were no significant associations between BRAFV600E and high-risk or multisystem disease.[Table: see text]

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

Chylothorax has rarely been reported as a pleuropulmonary complication of Waldenström macroglobulinaemia (WM). In general, when a unilateral effusion is discovered particularly in patients with a history of cancer or active malignancy, a broad differential including chylothorax needs to be considered. We present the case of a 50-year-old woman found to have chylothorax secondary to progression of WM as confirmed by cytology and presence of MYD88 L265P mutation in the pleural fluid specimen and subsequent resolution with chemotherapy. This review centres particularly on non-traumatic causes of chylothorax with a focus on WM and includes a unique patient perspective.

Abstract ObjectiveThe objective of this study was to identify the predictors of in-hospital mortality among patients with diffuse alveolar hemorrhage (DAH).Patients and MethodsWe conducted a retrospective review of 89 patients hospitalized for DAH at our institution between 2001 and 2017: 49 patients who died during hospitalization and 40 patients who survived were compared. We reviewed their presenting signs and symptoms, clinical course, radiologic and pathologic findings, along with medical management. We then performed univariate and multivariate analyses to identify the risk factors associated with in-hospital mortality.ResultsWe identified 12 factors to be associated with mortality when comparing survivor vs non-survivor cohorts: smoking (27 [67%] vs 21 [42%], p = 0.02), malignancy (7 [17%] vs 24 [49%], p = 0.002), interstitial lung disease (0 vs 7 [14%], p = 0.01), liver failure (1 [2%] vs 14 [28%], p = 0.001), autoimmune diseases (16 [40%] vs 4 [8%], p =0.0006), thrombocytopenia (3 [7%] vs 35 [71%], p <0.0001), ICU admission (23 [57%] vs 40 [85%], p=0.004), mean duration of ICU stay (3.5 days [± 6.7] vs 5.5 days [± 5.5], p = 0.4), steroid use (36 [90%] vs 31 [63%], p = 0.003), use of plasma exchange (6 [15%] vs 0, p = 0.005), use of mechanical ventilation (15 [37%] vs 36 [75%], p value = 0.0007) and development of acute respiratory distress syndrome (ARDS) (9 [22%] vs 37 [77%], p <0.0001), respectively. On multivariate analysis, thrombocytopenia (OR 52.08: 95% CI, 8.59-315.71; p <0.0001) and ARDS (OR 11.71: 95% CI, 2.60-52.67; p = 0.0013) were associated with higher odds of mortality in DAH while steroid use (OR 0.05: 95% CI, 0.007-0.39; p = 0.0004) was associated with a lower risk of in-hospital mortality in patients with DAH.ConclusionIn DAH, thrombocytopenia and ARDS were predictors of in-hospital mortality whereas the use of steroid was associated with a more favorable prognosis.

Background: Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder that is now recognized as a neoplasm by the World Health Organization. It is generally classified based on the site and extent of disease involvement (single system or multisystem). Pulmonary LCH (pLCH), an uncommon interstitial lung disease associated with smoking, often presents as isolated pulmonary disease. It is unclear whether patients with clinically isolated pLCH have extra-pulmonary lesions at diagnosis or during the course of their disease. The role of [18F] fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) in the staging of pLCH remains unclear. Our study aims to better characterize the utility of radiographic staging studies at time of diagnosis and prevalence of extrapulmonary disease at follow up in pLCH. Methods: We conducted a retrospective study of patients presenting with clinical findings consistent with isolated pLCH seen at the Mayo Clinic from January 2000 to January 2020. All patients had a diagnosis of pLCH determined by chest imaging studies [computed tomography (CT) or high-resolution CT (HRCT)] or by histopathologic findings from surgical or transbronchial lung biopsy. Histopathologic findings for the diagnosis of pLCH required the presence of Langerhans cells (S100+/CD1a+/Langerin+). Patients were excluded if they had clinically apparent extra-pulmonary organ involvement at the time of diagnosis. BRAF V600E mutation was determined by immunohistochemistry (IHC) or cell-free DNA (cfDNA). Staging was defined as FDG-PET-CT or whole body CT imaging obtained within 3 months of diagnosis of pLCH. Extra-pulmonary LCH involvement was determined by imaging characteristics or by histopathologic findings. Descriptive statistics and overall survival (OS) were analyzed with JMP software, version 14 (SAS Institute Inc., Cary, NC). Results: A total of 112 patients with clinically isolated pLCH were identified. The median age at diagnosis was 45 years (range 21-73), and 48 (43%) were male. The majority (n=110, 99%) were former or current smokers with a median pack year of 25 (range 1-57). Three (3%) patients were noted to have occupational industrial exposure. Nine patients had a history of another cancer prior to their diagnosis and staging of pLCH [lung (n=4), breast (n=2), neuroendocrine (n=2), thyroid (n=1)]. Presenting symptoms included dyspnea on exertion 49 (44%), cough 18 (16%), chest pain 14 (13%), and 29 (28%) were incidentally discovered on imaging studies. On HRCT, the following characteristics were observed: 42 (38%) cystic, 32 (29%) cystic and nodular, 37 (33%) nodular, 1 (&lt;1%) ground glass opacities. Seventy (63%) patients had lung biopsy confirmation, of which 11 (16%) patients underwent BRAF V600Emutation testing (7 by IHC, 4 by cfDNA). Six (55%) of these 11 patients were positive for BRAF V600E mutation. 34 (30%) patients underwent radiographic staging studies within 3 months of diagnosis of pLCH (25 FDG-PET-CT and 9 whole-body CT), and none of these imaging studies showed evidence of extra-pulmonary disease. Of the patients who had at least one year of follow-up (n=52), one (2%) developed extra-pulmonary disease. This patient did not undergo initial staging studies, developed headaches and was found to have a large calvarial lytic lesion within 2 months of pLCH diagnosis (BRAF V600E+). Among those who did not undergo staging at diagnosis (n=78), long term (&gt;5 years) follow up data were available for 23 (29%), and none developed extra-pulmonary disease as determined by clinical notes or imaging studies. No patient had evidence of new extra-pulmonary involvement or second malignancy at the time of last known follow-up. After a median follow-up duration of 2.4 years (95% CI: 1.5-3.6, range: 0.1-17) ten (9%) patients died, of which 5 died of pLCH related complications. The median OS for entire cohort was 15 years (95% CI 9.1-not reached, Figure 1). Conclusion: Our study shows that adult patients with clinically isolated pLCH rarely present with extra-pulmonary manifestations at diagnosis or at follow up. These findings suggest a limited role of routine radiographic staging studies in pLCH unless clinically indicated. Studies on longer follow up of this cohort would provide further insights into the natural history of pLCH and are underway. Disclosures Bennani: Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board; Kite/Gilead: Research Funding; Affimed: Research Funding. Shah:Dren Bio: Consultancy.

Abstract An ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has spread around the world. However, the clinical characteristics and outcomes of patients with COVID-19 related to different modes of exposure have not been well defined. We aimed to explore the clinical features and outcomes of COVID-19 related to one-time community exposure versus continuous household exposure. Retrospective case–control study involving COVID-19 patients admitted to a tertiary designated center in China was performed. Patients were enrolled if they had known exposure history of one-time community exposure or continuous household exposure. Twenty patients were compared in terms of demographic characteristics, clinical presentation, chest CT images, laboratory results, treatments, and clinical outcomes at 1-month follow-up. There were 10 patients in one-time community and continuous household exposure groups respectively. Males compromised 80% and 40% while the median ages were 37.5 and 51 years old in the 2 groups, respectively. Fever and cough were most common symptoms. Ground-glass opacities were presented on chest CT scan in 90% and 70% of the patients, and the median CT scores were 7 and 16 on admission, respectively. Three patients ranked severe in the community exposure group while 7 patients were severe or critical in household exposure group. On 1-month follow-up, all patients were improved clinically but COVID-19 IgG antibody detected positive. Median follow-up CT scores were 0 and 13 while pulmonary function test abnormalities were 0/9 and 2/7 in the 2 groups, respectively. COVID-19 patients with one-time community exposure tended to be mild in severity and had better outcomes, comparing to those with continuous household exposure.

Abstract Background: Combined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting.Methods: We conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE. Results: Among 228 patients with CPFE, 89 had fibrosis affecting <5% of their lungs, 54 had 5 to <10% fibrosis, and 85 had ≥10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p<0.001). In particular, among those with <5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to <10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis.Conclusions: Less severe (<5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed.Trial Registration: retrospectively registered