SUMMARY BackgroundChemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome.

Rituximab maintenance therapy after transplantation prolonged event-free survival, progression-free survival, and overall survival among patients with mantle-cell lymphoma who were younger than 66 years of age at diagnosis. (Funded by Roche and Amgen; LyMa ClinicalTrials.gov number, NCT00921414 .).

SUMMARY BackgroundGastrointestinal mucositis is defined as inflammation and/or ulcers of the gastrointestinal tract occurring as a complication of chemotherapy and radiation therapy, and affects about 50% of all cancer patients.

PURPOSE To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

Bacteremia remains a major cause of life-threatening complication in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture have been reported in cancer patients over the past years. The aim of our systematic review was to inventory the recent trends in epidemiology and antibiotic resistance of microorganisms causing bacteremia in cancer patients. Data for this review was identified by searches of Medline, Scopus and Cochrane Library for indexed articles and abstracts published in English since 2008. The principal search terms were: "antimicrobial resistance", "bacteremia", "bacterial epidemiology", "bloodstream infection", "cancer patients", "carbapenem resistance", "Escherichia coli resistance", "extended-spectrum β-lactamase producing E. coli", "febrile neutropenia", "fluoroquinolone resistance", "neutropenic cancer patient", "vancomycin-resistant Enterococcus", and "multidrug resistance". Boolean operators (NOT, AND, OR) were also used in succession to narrow and widen the search. Altogether, 27 articles were selected to be analyzed in the review. We found that Gram-negative bacteria were the most frequent pathogen isolated, particularly in studies with minimal use of antibiotic prophylaxis. Another important trend is the extensive emergence of antimicrobial-resistant strains associated with increased risk of morbidity, mortality and cost. This increasing incidence of antibiotic resistance has been reported in Gram-negative bacteria as well as in Gram-positive bacteria. This exhaustive review, reporting the recent findings in epidemiology and antibiotic resistance of bacteremia in cancer patients, highlights the necessity of local continuous surveillance of bacteremia and stringent enforcement of antibiotic stewardship programs in cancer patients.

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Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study (NCT04328298). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46–0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45–0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1–2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1–2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.

BackgroundBacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT. However, the impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. Our objective was to characterize the fecal microbiome collected before treatment to identify microbes that predict the risk of BSI.MethodsWe sampled 28 patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic stem cell transplantation (HSCT) prior to administration of chemotherapy and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We quantified bacterial taxa and used techniques from machine learning to identify microbial biomarkers that predicted subsequent BSI.ResultsWe found that patients who developed subsequent BSI exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome.ConclusionsThese results suggest that the gut microbiota can identify high-risk patients before HSCT and that manipulation of the gut microbiota for prevention of BSI in high-risk patients may be a useful direction for future research. This approach may inspire the development of similar microbiome-based diagnostic and prognostic models in other diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0301-4) contains supplementary material, which is available to authorized users.