Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM

Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL‐2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL‐2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non‐responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.     

Predictability and Inducibility of Detachment of Prostatic Central Gland Tissue after Prostatic Artery Embolization: Post Hoc Analysis of a Randomized Controlled Trial

Purpose

To assess the frequency and potential predictors of prostatic central gland tissue detachment (CGD), an enucleation-like reaction that sporadically occurred in a randomized controlled trial assessing efficacy and safety of prostatic artery embolization (PAE).

Neuroendokrine Neoplasien des Verdauungstrakts

best practice onkologie - Neuroendokrine Neoplasien (NEN) des Verdauungstrakts stellen eine heterogene Erkrankung mit variabler klinischer Manifestation dar. Sie machen etwa 1 % aller...     

Changes in gut microbial metagenomic pathways associated with clinical outcomes after the elimination of malabsorbed sugars in an IBS cohort

ABSTRACT

Specific diets to manage sugar malabsorption are reported to reduce clinical symptoms of irritable bowel syndrome (IBS). However, the effects of diets for malabsorbed sugars on gut microbiota signatures have not been studied, and associations with clinical outcomes in IBS have not been characterized. 22 IBS patients positively tested for either lactose-, fructose-, sorbitol- or combined malabsorptions were subjected to 2-weeks sugar elimination and subsequent 4-weeks re-introduction. 7 IBS patients tested negative for sugar malabsorption were used as controls. Nutrition and clinical symptoms were recorded throughout the study. Fecal samples were serially collected for 16S rRNA amplicon and shotgun-metagenome sequencing.

Dietary intervention supervised by nutrition counseling reduced IBS symptoms during the elimination and tolerance phases. Varying clinical response rates were observed between subjects, and used to dichotomize our cohort into visual analogue scale (VAS) responders and non-responders. Alpha -and beta-diversity analyzes revealed only minor differences regarding 16S rRNA-based fecal microbiota compositions between responder and non-responder patients during baseline or tolerance phase. In shotgun-metagenome analyzes, however, we analyzed microbial metabolic pathways and found significant differences in pathways encoding starch degradation and complex amino acid biosynthesis at baseline between IBS controls and malabsorbers, and notably, between diet responder and non-responders. Faecalibacterium prausnitzii, Ruminococcus spp. and Bifidobacterium longum largely informed these metabolic pathways.

Our study demonstrates that diet interventions for specific, malabsorbed carbohydrates reshaped the metagenomic composition of the gut microbiota, with a small community of bacterial taxa contributing to these changes rather than a single species.