Assessment of the efficacy and tolerability of ruxolitinib for the treatment of myelofibrosis patients in a real-life setting: An Italian MYNERVA Project.

BACKGROUND: Incorporating real-world data in the drug development process allows the improvement of health outcomes by providing better representation of actual patterns of drug safety and efficacy. AIMS AND METHODS: Here, we present the results of a retroprospective, observational real-life study of 154 patients with myelofibrosis treated with ruxolitinib in a real-life setting in seven Italian centers of the MYNERVA project. RESULTS: Median drug exposure was 29 (range, 3-98) months. Discontinuation rate was 27% after a median time of 13 (range, 3-61). While hematological toxicities were in line with previous findings, infections occurred frequently, representing a not negligible cause of discontinuation and death. Anemia, symptoms, and spleen responses were obtained at any time in 23%, 91%, and 68% of patients, respectively; most patients achieved their responses by week 24. Larger splenomegaly and delayed treatment initiation correlated with lower spleen response at 24 weeks. Spleen response was associated with a superior overall survival, regardless of DIPSS. Of interest, both achievement and loss of spleen response had prognostic implications. DISCUSSION AND CONCLUSION: Overall, our findings provide insights on the efficacy and safety of ruxolitinib in a real-world, multicenter cohort of Italian MF patients.

Logistics of an advanced therapy medicinal product during COVID-19 pandemic in Italy: successful delivery of mesenchymal stromal cells in dry ice.

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, Italian hospitals faced the most daunting challenges of their recent history, and only essential therapeutic interventions were feasible. From March to April 2020, the Laboratory of Advanced Cellular Therapies (Vicenza, Italy) received requests to treat a patient with severe COVID-19 and a patient with acute graft-versus-host disease with umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Access to clinics was restricted due to the risk of contagion. Transport of UC-MSCs in liquid nitrogen was unmanageable, leaving shipment in dry ice as the only option. METHODS: We assessed effects of the transition from liquid nitrogen to dry ice on cell viability; apoptosis; phenotype; proliferation; immunomodulation; and clonogenesis; and validated dry ice-based transport of UC-MSCs to clinics. RESULTS: Our results showed no differences in cell functionality related to the two storage conditions, and demonstrated the preservation of immunomodulatory and clonogenic potentials in dry ice. UC-MSCs were successfully delivered to points-of-care, enabling favourable clinical outcomes. CONCLUSIONS: This experience underscores the flexibility of a public cell factory in its adaptation of the logistics of an advanced therapy medicinal product during a public health crisis. Alternative supply chains should be evaluated for other cell products to guarantee delivery during catastrophes.

Assessment of eye length changes in accommodation using dynamic extended-depth OCT.

It has been suggested that accommodation induces increases in axial eye length which could contribute to the development of myopia. However, it is debated whether changes in eye length occur during accommodation as the degree of change varies widely across literature. In this study, an extended-depth optical coherence tomography (OCT) system that provides dynamic whole eye biometry was utilized to assess changes in lens thickness (LT) and axial eye length (AEL) in young subjects responding to step disaccommodation stimuli of amplitude 2D, 4D, and 6D. The decrease in lens thickness with disaccommodation was strongly correlated with stimulus amplitude. No statistically significant changes in AEL during accommodation were observed.

Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group.

In a previous publication on new terminology, definitions, and outcome criteria for immune thrombocytopenia (ITP), the International Working Group (IWG) on ITP acknowledged that response to treatment should consist of clinically meaningful end points such as bleeding manifestations and that platelet count may not be the ideal parameter for capturing the benefits of therapy. The IWG now proposes a consensus-based ITP-specific bleeding assessment tool (ITP-BAT) with definitions and terminology consistent with those adopted for other bleeding disorders. Bleeding manifestations were grouped into three major domains: skin (S), visible mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with grade 5 for any fatal bleeding. Bleeding reported by the patient without medical documentation is graded 1. Within each domain, the same grade is assigned to bleeding manifestations of similar clinical impact. The "worst bleeding manifestation since the last visit" (observation period) is graded (a suitable database collection form is provided), and the highest grade within each domain is recorded. The SMOG system provides a consistent description of the bleeding phenotype in ITP, and the IWG unanimously supports its adoption and validation in future clinical studies.