Unilateral leukemic infiltration and acute angle closure as the first sign of B-cell acute lymphoblastic leukemia relapse

Objective: Unilateral ocular leukemic infiltration with acute angle closure is an infrequent complication of B-cell acute lymphoblastic leukemia (ALL-B). We present a clinical case of leukemic ocular infiltration as the sole manifestation of ALL-B relapse. Methods: Case description Results: A 15-year-old female with a history of acute lymphoblastic leukemia in remission for 2 years and pulmonary tuberculosis treated in the past year presented with ocular redness and decreased visual acuity in the left eye (LE) with 5 days of evolution. Visual acuity was 20/20 in the right eye (RE) and absence of light perception in the left eye (LE). Biomicroscopy of LE showed a small hypopion, anterior chamber cells 4+, vitreous cells 3+, and a large white mass in the vitreous with associated vitreous hemorrhage in organization. In LE fundoscopy, the vitreous mass occupying most of the vitreous cavity and associated hemorrhage prevented retina visualization. B-scan ultrasound showed a multilobulated mass occupying virtually the entire vitreous cavity with associated choroidal detachment. Forty-eight hours later, she developed acute angle closure of LE with an IOP of 55 mmHg. A flow cytometric analysis of the anterior chamber and vitreous showed leukemic tumor cells. The microbiologic exam and PCR for Mycobacterium tuberculosis were negative. No other signs of relapse of the disease were identified after investigation by the oncology department. Rescue treatment of the underlying disease was started, with symptomatic improvement. Conclusion: Leukemic ocular infiltration can be the only manifestation of ALL-B relapse.info:eu-repo/semantics/publishedVersio

Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype

This study evaluated a panel including the molecular taxonomy subtype and the expression of 27 genes as a diagnostic tool to stratify bladder cancer patients at risk of aggressive behavior, using a well-characterized series of non-muscle invasive bladder cancer (NMIBC) as well as muscle-invasive bladder cancer (MIBC). The study was conducted using the novel NanoString nCounter gene expression analysis. This technology allowed us to identify the molecular subtype and to analyze the gene expression of 27 bladder-cancer-related genes selected through a recent literature search. The differential gene expression was correlated with clinicopathological variables, such as the molecular subtypes (luminal, basal, null/double negative), histological subtype (conventional urothelial carcinoma, or carcinoma with variant histology), clinical subtype (NMIBC and MIBC), tumor stage category (Ta, T1, and T2–4), tumor grade, PD-L1 expression (high vs. low expression), and clinical risk categories (low, intermediate, high and very high). The multivariate analysis of the 19 genes significant for cancer-specific survival in our cohort study series identified TP53 (p = 0.0001), CCND1 (p = 0.0001), MKI67 (p < 0.0001), and molecular subtype (p = 0.005) as independent predictors. A scoring system based on the molecular subtype and the gene expression signature of TP53, CCND1, or MKI67 was used for risk assessment. A score ranging from 0 (best prognosis) to 7 (worst prognosis) was obtained and used to stratify our patients into two (low [score 0–2] vs. high [score 3–7], model A) or three (low [score 0–2] vs. intermediate [score 3–4] vs. high [score 5–7], model B) risk categories with different survival characteristics. Mean cancer-specific survival was longer (122 + 2.7 months) in low-risk than intermediate-risk (79.4 + 9.4 months) or high-risk (6.2 + 0.9 months) categories (p < 0.0001; model A); and was longer (122 + 2.7 months) in low-risk than high-risk (58 + 8.3 months) (p < 0.0001; model B). In conclusion, the molecular risk assessment model, as reported here, might be used better to select the appropriate management for patients with bladder cancer

Clinical utility of checkpoint inhibitors against metastatic bladder cancer: overcoming challenges to find a way forward

Introduction: Cisplatin-based chemotherapy is currently considered the gold-standard treatment for metastatic urothelial carcinoma (mUC). Nevertheless, most mUC patients develop resistance to chemotherapy. Immune checkpoint inhibitors (ICI) have emerged as a therapeutic option for mUC. ICI are used as both first- and second-line therapy for patients with mUC but also for maintenance following chemotherapy and durable responses may be expected in these settings. Areas covered: Patients with mUC who experience progression after platinum-based chemotherapy regimens, those who are cisplatin-ineligible and have positive PD-L1 expression, and those who are platinum-ineligible, regardless of PD-L1 status, are the target population. The role of ICI monotherapy or drug combinations and newer proposals for mUC therapy are reviewed. The current status of biomarkers to guide ICI treatments in mUC is also provided, focusing on PD-L1, tumor mutational load, and liquid biopsies using ctDNA. Expert opinion: Current challenges to improve the role of ICI in mUC could be summarized as i) development of better drugs; ii) advances in drug-combinations schemes; iii) development of novel biomarkers and techniques to better select patients for this treatment; iv) providing the drugs in the optimal clinical setting; v) promoting trials covering more demographic and clinical heterogeneity (i.e. wider age range, gender, and diverse clinical representation)