Efficacy and safety of the third-generation chloroethylnitrosourea fotemustine for the treatment of chemorefractory T-cell lymphomas.

Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m(2) every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6–30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients’ subsets more likely to benefit from this approach

Beneficial fungi in the genus Trichoderma are effective control agents of noctuid moth larvae

Beneficial fungi belonging to the genus Trichoderma have well-known positive effects on plant biology, such as growth promotion, nutrients uptake efficiency, seed germination rate, influencing plant interactions with the environment and promoting plant defense against biotic and abiotic stress agents, including phytophagous insects. The fungal biocontrol agent T. afroharzianum strain T22 (T22) is capable to colonize the roots of tomato plants, eliciting an active response against insects. Here we obtained colonized tomato plants (var San Marzano nano) by coating the seeds with spores of Trichoderma afroharzianum strain T22 (T22-plant), and scored the plant-mediated effects of T22 on the moth Spodoptera littoralis (Lepidoptera: Noctuidae). Larvae fed with T22 plant leaves (T22-larvae) showed developmental delay and weight reduction associated with lower survival. Furthermore, T22-larvae showed an immunosuppressed phenotype, more susceptible, at both IV and VI instars, to sublethal doses of a biopesticide containing the entomopathogen Bacillus thuringiensis. The results obtained show a clear plant-mediated effect of T. afroharzianum on S. littoralis larvae, which could contribute to the reduction of pesticide use in agriculture by suppressing this pest or enhancing its susceptibility to biocontrol agents

Selection of Endophytic Beauveria bassiana as a Dual Biocontrol Agent of Tomato Pathogens and Pests

Endophytic fungi (EF) can enhance both plant growth and defense barriers against pests and pathogens, contributing to the reduction of chemical pesticides and fertilizers use in agriculture. Beauveria bassiana is an entomopathogenic fungus showing endophytism in several crops, often associated with a good capacity to limit the development of pests and disease agents. However, the diversity of the protective efficacy and plant response to different strains can be remarkable and needs to be carefully assessed for the successful and predictable use of these beneficial microorganisms. This study aims to select B. bassiana strains able to colonize tomato plants as endophytes as well as to control two important disease agents, Botrytis cinerea and Alternaria alternata, and the pest aphid, Macrosiphum euphorbiae. Nine wild-type isolates and one commercial strain were screened for endophytism, then further characterized for plant-growth promotion plus inhibition of disease development and pest infestation. Four isolates proved to have a good control activity against the biotic stressors tested, but only Bb716 was also able to promote plant growth. This work provides a simple workflow for the selection of beneficial EF, paving the way towards more effective use of B. bassiana in Integrate Pest Management (IPM) of tomato

Un fungo del genere Trichoderma conferisce resistenza al pomodoro nei confronti delle larve di Spodoptera littoralis alterando il ruolo simbiotico del loro microbiota intestinale

I funghi benefici del genere Trichoderma sono importanti agenti di biocontrollo di patogeni e promuovono la crescita delle piante. In questo lavoro si dimostra che l’interazione tra la pianta di pomodoro e la larva del lepidottero Spodoptera littoralis (Lepidoptera, Noctuidae) viene modulata dal loro microbiota. In particolare, viene descritto il meccanismo grazie al quale la colonizzazione radicale da parte del ceppo T22 di Trichoderma afroharzianum è in grado di conferire alla pianta resistenza nei confronti dell’insetto fitofago. Le larve alimentate con piante di pomodoro colonizzate da T22 mostrano una significativa riduzione della crescita, un marcato ritardo nello sviluppo e una elevata mortalità rispetto ai controlli. Per comprendere le basi funzionali delle alterazioni fenotipiche osservate nelle larve di S. littoralis, che potrebbero essere determinate da una ridotta funzionalità intestinale del fitogafo causata dall’induzione fungina delle barriere di difesa della pianta, sono state valutate le possibili alterazioni strutturali e funzionali di questo organo e del microbiota ad esso associato tramite un approccio morfologico, fisiologico e molecolare. I cambiamenti indotti nella pianta di pomodoro da T. afroharzianum non provocano alcun danno strutturale all’intestino medio delle larve di S. littoralis e/o alterazioni della capacità digestiva, ma determinano una severa disbiosi intestinale. Composizione e funzionalità del microbiota risultano significativamente alterate e questo determina un ridotto supporto nutrizionale con conseguente impatto negativo sullo sviluppo e sulla sopravvivenza del fitofago. Questi effetti possono essere completamente eliminati con la somministrazione orale del microbiota intestinale delle larve controllo o del batterio Enterococcus casseliflavus, il simbionte responsabile della maggior parte dei cambiamenti trascrizionali osservati a carico del microbiota. I risultati ottenuti permettono di fare luce sul meccanismo con il quale un microrganismo del suolo è in grado di regolare l’interazione tra un fitofago e una pianta. La comprensione di questa modulazione, guidata dalla competizione tra organismi per le risorse trofiche, pone le basi per lo sviluppo di nuove strategie per valutare l’impatto ecologico degli agenti di biocontrollo, e quindi per una gestione sostenibile degli agroecosistemi

Glycosyl-phosphatidyl-inositol-defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the emergence of a GPI-defective clonal hematopoiesis. Its clinical features are hemolytic anemia, cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI-defective in PNH patients. This study aims to investigate the granulocyte functional properties in PNH. We analyzed bacterial-dependent intracellular ingestion and the consequent activation of oxidative burst in GPI-defective granulocytes from four neutropenic PNH patients. Our data show a significant increase in the ability of GPI-defective granulocytes to ingest opsonized bacteria. In addition, an impaired respiratory burst effectiveness in response to two independent bacterial stimuli, the N-formyl-MetLeuPhe (fMLP) synthetic bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and the severe impairment of oxidative burst, occurring in chronic granulomatosis disease, were unable to significantly affect phagocytosis. Thus, additional mechanisms, able to differentially affect ingestion ability and respiratory burst effectiveness, have to be hypothesized. The reduced burst effectiveness of GPI-defective granulocytes was maintained after treatment with phorbol 12-myristate 13-acetate, a pharmacological stimulus able to extensively recruit and to trigger intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed to severely affect granulocyte respiratory burst with a mild effect on the phagocytosis. These data suggest a role for a modulation of intracellular PKC in the pathogenesis of the impaired granulocyte oxidative burst