The clinical importance of moderate/severe bone marrow fibrosis in patients with therapy-related myelodysplastic syndromes.

The presence of moderate to severe bone marrow (BM) fibrosis has been shown to be an adverse feature in patients with primary myelodysplastic syndromes (MDS). However, the clinical importance of BM fibrosis is not clear in therapy-related MDS. We retrieved all therapy-related MDS (t-MDS) cases (n = 266) diagnosed at our hospital over a 10-year period (2003-2012). Reticulin and trichrome stains were performed in cases in which BM fibrosis was suspected on initial evaluation of hematoxylin and eosin-stained slide. BM fibrosis was graded according to European consensus guidelines, and a score of MF2/MF3 was defined as moderate/severe fibrosis. Moderate/severe BM fibrosis was found in 47 (17%) patients. Compared to 219 patients with no/mild BM fibrosis, the patients with moderate/severe fibrosis presented with severer thrombocytopenia (p = 0.039) and higher numbers of circulating blasts (p = 0.051) but with similar degrees of anemia and neutropenia, transfusion requirements, and similar incidences of hepatosplenomegaly and constitutional symptoms. Histological examination revealed a comparable BM cellularity and BM blast percentage, but markedly increased megakaryocytes (p < 0.001) in the fibrotic group. Although the risk distribution of cytogenetic data was similar according to the New Comprehensive Cytogenetic Scoring criteria, -5 and -17 were more frequently observed in t-MDS with moderate/severe BM fibrosis (p = 0.031 and p = 0.043, respectively). With a median follow-up of 11.5 months, patients with moderate/severe BM fibrosis showed a similar risk of acute myeloid leukemia transformation and a comparable overall survival in univariate and multivariate analyses. Moderate/severe BM fibrosis in patients with t-MDS is associated with certain clinicopathological and genetic features. However, unlike the situation in patients with primary MDS, moderate/severe BM fibrosis does not add additional risk to patients with therapy-related MDS.

Default predicted no-effect target concentrations for antibiotics in the absence of data for the protection against antibiotic resistance and environmental toxicity.

The pharmaceutical manufacturing industry, via the AMR Industry Alliance, has developed and implemented steps to help minimize the potential impact of pharmaceutical manufacturing on the spread of antimicrobial resistance (AMR). One of these steps was to publish predicted no-effect concentrations (PNECs) to serve as targets for antibiotic manufacturing wastewater effluent risk assessments aimed to help protect environmental receptors and to mitigate against the spread of antibiotic resistance. Concentrations below which adverse effects in the environment are not expected to occur (PNECs) were first published in 2018 and are updated annually. The current list now stands at 125 antibiotics; however, it is recognized that this list does not encompass all manufactured antibiotics. Therefore, a statistical evaluation of currently available data was conducted and a default PNEC of 0.05 µg/L for antibiotics in the absence of other data was derived. Integr Environ Assess Manag 2022;18:863-867. © 2022 Merck, Sanofi, Johnson & Johnson Services, Inc, F.Hoffmann-La Roche Ltd, Teva Pharmaceuticals, GlaxoSmithKline, Novartis Pharma AG, and Pfizer lnc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).