Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

Introduction: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicentre observational study evaluating bendamustine toxicity in real-world practice. Methods: Patients receiving at least one dose of bendamustine (B) +/- rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details and grade 3-5 adverse events (AEs) were analysed. Results: 323 patients were enrolled from 9 NHS hospitals. Most patients (96%) received BR and 46% R maintenance. 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%), and the relative risk highest during maintenance (54%), induction (34%) and follow-up (28%). Toxicity led to permanent treatment discontinuation in 13% of patients, and 2.8% died of bendamustine-related infections (n=5), myelodysplastic syndrome (n=3), and cardiac disease (n=1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor pre-induction PS, poor pre-maintenance PS, abnormal pre-induction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3/10 opportunistic infections occurred despite prophylaxis. Conclusion: In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to trial populations of younger, fitter patients. Poor PS, mantle cell histology and maintenance rituximab were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death warranting extended antimicrobial prophylaxis and infectious surveillance, especially in maintenance-treated patients

No differences in soil carbon stocks across the tree line in the Peruvian Andes

Reliable soil organic carbon (SOC) stock measurements of all major ecosystems are essential for predicting the influence of global warming on global soil carbon pools, but hardly any detailed soil survey data are available for tropical montane cloud forests (TMCF) and adjacent high elevation grasslands above (puna). TMCF are among the most threatened of ecosystems under current predicted global warming scenarios. We conducted an intensive soil sampling campaign extending 40 km along the tree line in the Peruvian Andes between 2994 and 3860 m asl to quantify SOC stocks of TMCF, puna grassland, and shrubland sites in the transition zone between the two habitats. SOC stocks from the soil surface down to the bedrock averaged (±standard error SE) 11.8 (±1.5, N = 24) kg C/m2 in TMCF, 14.7 (±1.4, N = 9) kg C/m2 in the shrublands and 11.9 (±0.8, N = 35) kg C/m2 in the grasslands and were not significantly different (P > 0.05 for all comparisons). However, soil profile analysis revealed distinct differences, with TMCF profiles showing a uniform SOC distribution with depth, shrublands a linear decrease, and puna sites an exponential decrease in SOC densities with soil depth. Organic soil layer thickness reached a maximum (~70 cm) at the upper limit of the TMCF and declined with increasing altitude toward puna sites. Within TMCF, no significant increase in SOC stocks with increasing altitude was observed, probably because of the large variations among SOC stocks at different sites, which in turn were correlated with spatial variation in soil depth