A Retrospective Cohort Study to Determine Real-World Treatment Patterns in Patients with Sézary Syndrome in the United States.

INTRODUCTION: Sézary syndrome (SS) is a rare leukemic cutaneous T cell lymphoma. This study was conducted to examine the real-world treatment patterns among patients with SS in the USA from 2018 to 2020. METHODS:  This was a retrospective cohort study using the Symphony Health Solutions claims database. Adult patients with ≥ 1 diagnosis code for SS were classified into three non-mutually exclusive cohorts: 2018, 2019, and 2020. Patient characteristics and treatment patterns were examined across the 3 years of study and reported descriptively for each year. Annual treatment patterns were also described for the five states with the highest proportions of SS patients in 2020. RESULTS: Overall, 869, 882, and 853 SS patients were identified in 2018, 2019, and 2020, respectively (median age: 70 years for each year; male: 54.4%, 54.8%, and 55.6%, respectively). The use of any systemic and parenteral systemic treatments increased over time. While utilization rates for many specific systemic therapies decreased over the study period, mogamulizumab use increased, making it the most commonly used systemic treatment in 2020 (29.2%) among patients with any systemic treatment. The five states with the highest proportions of SS patients in 2020 were Florida, New York, California, Texas, and Pennsylvania. Systemic treatment patterns varied considerably by state. CONCLUSION: Some systemic therapies showed decreased usage over time while a few showed increased utilization, with mogamulizumab showing the largest increase. Treatment patterns for SS varied by region. Further research is needed to examine the factors that drive treatment selection for patients with SS.

Clinical features of persistent postural-perceptual dizziness coexisting with Meniere's disease in comparison with Meniere's disease alone.

Background: Persistent postural-perceptual dizziness (PPPD) is a chronic vestibular syndrome often triggered by acute or episodic vestibular syndromes, such as Meniere's disease (MD). According to the diagnostic criteria, PPPD may coexist with other structural diseases, and the evidence of another active illness does not necessarily exclude PPPD diagnosis. However, persistent symptoms, even those meeting the PPPD criteria even long after Meniere's attack, are often overlooked as potential PPPD precipitated by MD. Some clinicians overlook PPPD in such patients, treating them solely for MD once diagnosed. Since a treatment strategy for PPPD is completely different from that for MD, this may result in the deprivation of adequate treatments. Objectives: To emphasize the importance of diagnosing PPPD coexisting with MD including not treating such patients solely for MD, and to compare the clinical features of PPPD and MD. Methods: Vestibular function tests, including canal paresis (CP)%, c- and o-vestibular myogenic potentials, vestibulo-ocular reflex-direction preponderance, and posturography and clinical symptom scales, including the Dizziness Handicap Inventory, Niigata PPPD Questionnaire, and Hospital Anxiety and Depression Scale, were compared between 105 PPPD patients with MD or other precipitants and 130 patients with MD alone. The clinical symptom scales were further compared between 23 patients with PPPD coexisting with MD and those with MD alone. Results: The CP% was significantly higher in patients with MD than in those with PPPD. However, the total and subscores of all three clinical symptom scales were higher in patients with PPPD than in those with MD. The total score on all clinical symptom scales was higher in patients with PPPD coexisting with MD than in those with MD alone. Conclusion: Persistent postural-perceptual dizziness development from a precipitating MD may be associated with more severe clinical symptoms. Thus, clinical symptom scales may be useful for detecting PPPD in patients with Meniere's disease.

Fetal liver CD34+ contain human immune and endothelial progenitors and mediate solid tumor rejection in NOG mice.

BACKGROUND: Transplantation of CD34+ hematopoietic stem and progenitor cells (HSPC) into immunodeficient mice is an established method to generate humanized mice harbouring a human immune system. Different sources and methods for CD34+ isolation have been employed by various research groups, resulting in customized models that are difficult to compare. A more detailed characterization of CD34+ isolates is needed for a better understanding of engraftable hematopoietic and potentially non-hematopoietic cells. Here we have performed a direct comparison of CD34+ isolated from cord blood (CB-CD34+) or fetal liver (FL-CD34+ and FL-CD34+CD14-) and their engraftment into immunocompromised NOD/Shi-scid Il2rgnull (NOG) mice. METHODS: NOG mice were transplanted with either CB-CD34+, FL-CD34+ or FL-CD34+CD14- to generate CB-NOG, FL-NOG and FL-CD14--NOG, respectively. After 15-20 weeks, the mice were sacrificed and human immune cell reconstitution was assessed in blood and several organs. Liver sections were pathologically assessed upon Haematoxylin and Eosin staining. To assess the capability of allogenic tumor rejection in CB- vs. FL-reconstituted mice, animals were subcutaneously engrafted with an HLA-mismatched melanoma cell line. Tumor growth was assessed by calliper measurements and a Luminex-based assay was used to compare the cytokine/chemokine profiles. RESULTS: We show that CB-CD34+ are a uniform population of HSPC that reconstitute NOG mice more rapidly than FL-CD34+ due to faster B cell development. However, upon long-term engraftment, FL-NOG display increased numbers of neutrophils, dendritic cells and macrophages in multiple tissues. In addition to HSPC, FL-CD34+ isolates contain non-hematopoietic CD14+ endothelial cells that enhance the engraftment of the human immune system in FL-NOG mice. We demonstrate that these CD14+CD34+ cells are capable of reconstituting Factor VIII-producing liver sinusoidal endothelial cells (LSEC) in FL-NOG. However, CD14+CD34+ also contribute to hepatic sinusoidal dilatation and immune cell infiltration, which may culminate in a graft-versus-host disease (GVHD) pathology upon long-term engraftment. Finally, using an HLA-A mismatched CDX melanoma model, we show that FL-NOG, but not CB-NOG, can mount a graft-versus-tumor (GVT) response resulting in tumor rejection. CONCLUSION: Our results highlight important phenotypical and functional differences between CB- and FL-NOG and reveal FL-NOG as a potential model to study hepatic sinusoidal dilatation and mechanisms of GVT.

Safety and efficacy of neoadjuvant chemotherapy with paclitaxel, carboplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma.

BACKGROUND: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen. METHODS: We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75 years and those with an estimated glomerular filtration rate (eGFR) < 60 mL/min were classified as ineligible for cisplatin. RESULTS: The median age was 70 (27-81) years. The median eGFR at treatment initiation was 63.2 (41.1-89.7) mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed. CONCLUSION: NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy.

Prognostic Biomarkers of Mortality in Older Patients Without Cancer in Home Healthcare.

Introduction The number of patients without cancer who receive home healthcare is increasing; however, prognostic prediction is challenging among them. This study aimed to investigate the prognostic value of generic biomarkers for mortality in patients without cancer who receive home healthcare. Materials and methods The multicenter retrospective cohort study included 114 older patients without cancer, of which 12 (10.5%) died during the study period. The median (interquartile range (IQR)) of the study observation period was 181 (49-293) days. Generic biomarkers included hemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). A multivariate-adjusted Cox proportional hazard model on all-cause mortality was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) for each biomarker. The cut-off values of each biomarker were calculated by receiver operating characteristic curve analysis. The performance of cut-off values was evaluated by time-dependent area under the curves (AUCs). Results The median (IQR) of AST was 13 (10-21) U/L. The biomarkers significantly predictive of mortality were Hb (fully adjusted HR: 0.41; 95% Cl: 0.25 - 0.70), Alb (HR: 0.41; 95% Cl: 0.02 - 0.69), and AST (HR: 1.09; 95% Cl: 1.00 - 1.18), along with male sex (HR: 4.07; 95% Cl: 1.15 - 14.35). The AUC of a cut-off value of AST (> 31 U/L) at 360 days was 0.72 (95% CI 0.71 - 0.72; p < 0.01), which outperformed the AUCs for Hb and Alb. Conclusion AST, in addition to Hb and Alb, may be useful for predicting the prognosis of older patients without cancer, who had a normal-to-mild increased level of AST, in home healthcare settings. Larger-sample and longer follow-up studies will be warranted.