A comprehensive case study on successful multimodal therapy in philadelphia chromosome-positive acute myeloid leukemia with NPM1 and IDH2 mutations.

A 67-year-old female came to Tampa General Hospital with Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) featuring an intriguing combination of mutations, including NPM1 and IDH2 mutations. Novel combination therapy with azacitidine, venetoclax and ponatinib allowed her to successfully achieve a complete response (CR) and undergo an allogeneic hematopoietic stem cell transplant (HSCT). This case report provides an overview of her clinical course, emphasizing the significance of integrated therapy and the challenges associated with balancing treatment for AML. It also underscores the importance of a multidisciplinary approach and careful monitoring of patients with complex hematologic conditions.

Targeting CD22 for the Treatment of B-Cell Malignancies.

Immunotherapeutic agents play an increasingly important role in the treatment of B-cell malignancies. CD19 and CD20 are common targets for lymphoid malignancies, though patients who relapse have few therapeutic options remaining. CD22 is a cell surface sialoglycoprotein uniquely present on B-cells and regulates B-cell function and proliferation. Thus, it is an appealing therapeutic target for autoimmune disorders and B-cell malignancies. A variety of therapies targeting CD22 have been developed, including monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, chimeric antigen receptor T cells, and bispecific antibodies. Here, we review the biology of CD22 and key therapies targeting CD22 in lymphoid malignancies.

Racial and Socioeconomic Disparities in Mantle Cell Lymphoma.

BACKGROUND: Although race and socioeconomic factors are associated with outcome in many malignancies, few studies have examined the effect of race and socioeconomic status on patients with mantle cell lymphoma (MCL). PATIENTS AND METHODS: We used the National Cancer Database to identify patients with MCL diagnosed between 2004 and 2013. We used χ2 and analysis of variance to assess associations of covariates with race/ethnicity. For univariate and multivariable analyses of overall survival (OS) we used Cox proportional hazards models. OS from the time of diagnosis was the primary end point. RESULTS: Of 18,120 MCL patients, 14,984 (83%) were white non-Hispanic (NH), 709 (4%) black NH, and 1096 (6%) Hispanic. Of these patients, 6798 (39%) had private insurance, 9520 (55%) Medicare, and 635 (4%) Medicaid. Compared with white NH race, black race was associated with treatment at an academic/research program (347 of 681 patients [51%] vs. 5577 of 14,851 [38%]), B symptoms (196 patients [28%] vs. 3 [25%]), Medicaid/uninsured status (101 patients [15%] vs. 642 [5%]), and residence in regions with lower average education and income (all P < .001). Compared with NH black and Hispanic patients, more white NH patients received stem cell transplantation (73 patients [10%] vs. 114 [10%] vs. 1891 [13%]; P < .001). In multivariable analysis, Hispanic ethnicity, private insurance, and treatment at an academic center were associated with better OS (5-year OS 55.8%, 66.2%, and 56.6%, respectively), whereas black race was associated with inferior OS (5-year OS 46.8%). CONCLUSION: We identified disparities according to race and ethnicity in OS, independent of insurance and socioeconomic status. Further assessment of treatment patterns might elucidate new targets for improving access to care and health outcomes for rare cancers.

Intravitreal and subconjunctival melphalan for retinoblastoma in transgenic mice.

Purpose. To measure the chemotherapeutic effects of focal melphalan (intravitreal and subconjunctival) on tumor burden, hypoxia, and vasculature in LHBETATAG murine retinoblastoma model. Methods. LHBETATAG transgenic mice were treated with a single 1 mcg intravitreal injection of melphalan, 100 mcg subconjunctival injection, or semiweekly 10 mcg subconjunctival injections for 3 weeks. At 1 or 3 weeks, eyes were enucleated, serially sectioned, and processed with haematoxylin and eosin (H&E) for tumor burden measurements and probed with immunofluorescence to analyze tumor hypoxia and vasculature. Results. Focal melphalan significantly reduced retinal tumor size (P < 0.02) when given intravitreally or subconjunctivally. Eyes treated with a one-time intravitreal injection of 1 mcg melphalan had significantly smaller tumors at both 1 week (P = 0.017) and at 3 weeks after injection (P = 0.005). Intratumoral hypoxia showed a significant decline in hypoxia at 1 week following intravitreal injection and after maximum dosage of subconjunctival melphalan. Total vasculature was not significantly affected following intravitreal administration. Conclusion. Focal delivery of melphalan via intravitreal or subconjunctival injection has a significant effect on reducing tumor burden, hypoxia, and vasculature, in the treatment of murine retinoblastoma tumors.

Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 µM PolyGem was equivalent in tumor cell toxicity to 1 µM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.