Patterns of leukocyte recovery predict infectious complications after CD19 CAR-T cell therapy in a real-world setting.

BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. METHODS: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. RESULTS: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months). CONCLUSIONS: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.

Clinically localized type 1 and 2 papillary renal cell carcinomas have similar survival outcomes following surgery / Los carcinomas papilares de células renales tipo 1 y 2 localizados clínicamente tienen resultados de supervivencia similares después de la cirugía

Propósito Se intentó determinar la incidencia, hallazgos patológicos, factores pronósticos y resultados clínicos para pacientes con CCR papilar clínicamente localizado. Métodos Demográfico, Se recopilaron hallazgos clínicos y patológicos en todos los pacientes con CCRP sometidos a cirugía en cuatro centros médicos académicos. El punto final primario fue la supervivencia específica del cáncer (CSS). La supervivencia sin recaída (RFS) y la supervivencia general (OS) fueron puntos finales secundarios. Kaplan- Se obtuvieron estimaciones de Meier y se usaron modelos de regresión de riesgos proporcionales de Cox para evaluar predictores de mortalidad y recaída. Resultados Identificamos 626 CCPR, de los cuales 373 (60por ciento) fueron del tipo 1 y 253 (40 por ciento) fueron del tipo 2, con tres cuartas partes de todos los tumores siendo pT1. En comparación con los pacientes con tipo 1, aquellos con tipo 2 eran mayores (edad media: 63 frente a 61; (AU)

Purpose We aimed to determine incidence, pathologic fndings, prognostic factors and clinical outcomes for patients with clinically localized papillary RCC. Methods Demographic, clinical and pathologic fndings were collected on all patients with PRCC undergoing sur-gery at four academic medical centers. The primary end-point was cancer-specifc survival (CSS). Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Kaplan­ Meier estimates were obtained, and Cox proportional hazard regression models were used to assess predictors of mortality and relapse. Results We identifed 626 PRCC, of which 373 (60 pertcent) were type 1 and 253 (40 pertcent) were type 2, with three-quar-ters of all tumors being pT1. Compared to patients with type 1, those with type 2 were older (mean age: 63 vs 61; (AU)

Clinically localized type 1 and 2 papillary renal cell carcinomas have similar survival outcomes following surgery.

PURPOSE: We aimed to determine incidence, pathologic findings, prognostic factors and clinical outcomes for patients with clinically localized papillary RCC. METHODS: Demographic, clinical and pathologic findings were collected on all patients with PRCC undergoing surgery at four academic medical centers. The primary endpoint was cancer-specific survival (CSS). Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Kaplan-Meier estimates were obtained, and Cox proportional hazard regression models were used to assess predictors of mortality and relapse. RESULTS: We identified 626 PRCC, of which 373 (60 %) were type 1 and 253 (40 %) were type 2, with three-quarters of all tumors being pT1. Compared to patients with type 1, those with type 2 were older (mean age: 63 vs 61; p = 0.02), presented more commonly with symptoms (13 vs 7 %; p = 0.02) and had larger mean tumor size (5.2 vs 4.3 cm; p = 0.001). With a median follow-up of 41 months (IQR: 16-68), 92 patients had died of PRCC (15 %), 48 (8 %) experienced relapse, and 101 died from all causes (16 %). The estimated 5-year CSS, RFS and OS were 83, 91 and 82 %, respectively. In multivariable analysis, older age, T stage and nodal status were predictors of CSS and OS. However, PRCC subtype was not a predictor of CSS, RFS or OS. CONCLUSION: While patients with type 2 PRCC appear to present with more advanced disease than patients with type 1, PRCC subtype does not appear to be an independent predictor of CSS, RFS or OS for treated localized disease.

Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus.

BACKGROUND: The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. METHODS: Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. RESULTS: Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. CONCLUSION: That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

Na(+)/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer: molecular characterization of SMCT.

We report an extensive characterization of the Na(+)/monocarboxylate transporter (SMCT), a plasma membrane protein that mediates active transport of monocarboxylates such as propionate and nicotinate, and we show that SMCT may play a role in colorectal cancer diagnosis. SMCT, the product of the SLC5A8 gene, is 70% similar to the Na(+)/I(-) symporter, the protein that mediates active I(-) uptake in the basolateral surface of thyrocytes and other cells. SMCT was reported in the apical surface of thyrocytes and formerly proposed also to transport I(-) and was called the apical I(-) transporter. However, it is now clear that SMCT does not transport I(-). Here we demonstrate a high-affinity Na(+)-dependent monocarboxylate transport system in thyroid cells, which is likely to be SMCT. We show that, whereas thyroidal Na(+)/I(-) symporter expression is thyroid-stimulating hormone (TSH)-dependent and basolateral, SMCT expression is TSH-independent and apical not only in the thyroid but also in kidney and colon epithelial cells and in polarized Madin-Darby canine kidney cells. We determine the kinetic parameters of SMCT activity and show its inhibition by ibuprofen (K(i) = 73 +/- 9 microM) in Xenopus laevis oocytes. SMCT was proposed to be a tumor suppressor in colon cancer. Significantly, we show that higher expression of SMCT in colon samples from 113 colorectal cancer patients correlates with longer disease-free survival, suggesting that SMCT expression may be a favorable indicator of colorectal cancer prognosis.