Molecular measurable residual disease (MRD) assessment is not established in approximately 60% of acute myeloid leukemia (AML) patients because of the lack of suitable markers for quantitative real-time polymerase chain reaction. To overcome this limitation, we established an error-corrected next-generation sequencing (NGS) MRD approach that can be applied to any somatic gene mutation. The clinical significance of this approach was evaluated in 116 AML patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) in complete morphologic remission (CR). Targeted resequencing at the time of diagnosis identified a suitable mutation in 93% of the patients, covering 24 different genes. MRD was measured in CR samples from peripheral blood or bone marrow before alloHCT and identified 12 patients with persistence of an ancestral clone (variant allele frequency [VAF] >5%). The remaining 96 patients formed the final cohort of which 45% were MRD (median VAF, 0.33%; range, 0.016%-4.91%). In competing risk analysis, cumulative incidence of relapse (CIR) was higher in MRD than in MRD patients (hazard ratio [HR], 5.58; < .001; 5-year CIR, 66% vs 17%), whereas nonrelapse mortality was not significantly different (HR, 0.60; = .47). In multivariate analysis, MRD positivity was an independent negative predictor of CIR (HR, 5.68; < .001), in addition to - and mutation status at the time of diagnosis, and of overall survival (HR, 3.0; = .004), in addition to conditioning regimen and and mutation status. In conclusion, NGS-based MRD is widely applicable to AML patients, is highly predictive of relapse and survival, and may help refine transplantation and posttransplantation management in AML patients.

We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia from MDS (sAML) to evaluate their impact on prognosis. 304 patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). In multivariate analysis, mutated NRAS, U2AF1, IDH2, TP53 and/or a complex karyotype were significant prognostic markers for OS besides age above 60 years, remission status, IPSS-R cytogenetic risk, HCT-CI > 2 and female donor sex. Mutated NRAS, IDH1, EZH2 and TP53 and/or a complex karyotype were

Antimicrobial resistance is a major public health issue caused by antibiotic overuse and misuse. Antimicrobial stewardship (AMS) has been increasingly endorsed worldwide, but its effect has been studied scarcely in urologic settings. A before-after study was performed from 2018 through 2020 to evaluate changes in antimicrobial prescription, resistance rates and clinical safety upon implementation of an AMS audit and feedback program in the Urology Department of a large German academic medical center. The primary endpoints were safety clinical outcomes: the rate of infection-related readmissions and of infectious complications after transrectal prostate biopsies. Resistance rates and antimicrobial consumption rates were the secondary endpoints. The AMS team reviewed 196 cases (12% of all admitted in the department). The overall antibiotic use dropped by 18.7%. Quinolone prescriptions sank by 78.8% (p = 0.02) and 69.8% (p > 0.05) for ciprofloxacin and levofloxacin, respectively. The resistance rate of E. coli isolates declined against ceftriaxone (−9%), ceftazidime (−12%) and quinolones (−25%) in the AMS period. No significant increase in infection-related readmissions or infectious complications after prostate biopsies was observed (p = 0.42). Due to the potential to reduce antibiotic use and resistance rates with no surge of infection-related complications, AMS programs should be widely implemented in urologic departments.