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Preclinical models have shown that blocking PD-1/PD-L1 pathways enhances antileukemic responses. Azacitidine upregulates PD-1 and IFNγ signaling. We therefore conducted this single-arm trial, in which patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) were treated with azacitidine 75 mg/m2 days 1 to 7 intravenously or subcutaneously with nivolumab 3 mg/kg intravenously on days 1 and 14, every 4 to 6 weeks. For the seventy patients who were treated, the median age was 70 years (range, 22–90) and the median number of prior therapies received was 2 (range, 1–7). The overall response rate (ORR) was 33%, including 15 (22%) complete remission/complete remission with insufficient recovery of counts, 1 partial response, and 7 patients with hematologic improvement maintained >6 months. Six patients (9%) had stable disease >6 months. The ORR was 58% and 22%, in hypomethylating agent (HMA)–naïve (n = 25) and HMA-pretreated (n = 45) patients, respectively. Grade 3 to 4 immune-related adverse events occurred in 8 (11%) patients. Pretherapy bone marrow and peripheral blood CD3 and CD8 were significantly predictive for response on flow cytometry. CTLA4 was significantly upregulated on CD4+ Teff in nonresponders after 2 and 4 doses of nivolumab. Azacitidine and nivolumab therapy produced an encouraging response rate and overall survival in patients with R/R AML, particularly in HMA-naïve and salvage 1 patients. Pretherapy bone marrow aspirate and peripheral blood CD3 percentage may be biomarkers for patient selection. Significance: Azacitidine in combination with nivolumab appeared to be a safe and effective therapy in patients with AML who were salvage 1, prior hypomethylator-naïve, or had increased pretherapy CD3+ bone marrow infiltrate by flow cytometry or IHC. Bone marrow CD3 and CD8 are relatively simple assays that should be incorporated to select patients in future trials. This article is highlighted in the In This Issue feature, p. 305

Background Phenotypic characterization of immune cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) is lacking. Methods T‐cell infiltration was quantified on BM biopsies from 13 patients with AML, and flow cytometry was performed on BM aspirates (BMAs) from 107 patients with AML who received treatment at The University of Texas MD Anderson Cancer Center. The authors evaluated the expression of inhibitory receptors (programmed cell death protein 1 [PD1], cytotoxic T‐lymphocyte antigen 4 [CTLA4], lymphocyte‐activation gene 3 [LAG3], T‐cell immunoglobulin and mucin‐domain containing‐3 [TIM3]) and stimulatory receptors (glucocorticoid‐induced tumor necrosis factor receptor‐related protein [GITR], OX40, 41BB [a type 2 transmembrane glycoprotein receptor], inducible T‐cell costimulatory [ICOS]) on T‐cell subsets and the expression of their ligands (41BBL, B7‐1, B7‐2, ICOSL, PD‐L1, PD‐L2, and OX40L) on AML blasts. Expression of these markers was correlated with patient age, karyotype, baseline next‐generation sequencing for 28 myeloid‐associated genes (including P53), and DNA methylation proteins (DNA methyltransferase 3α, isocitrate dehydrogenase 1[IDH1], IDH2, Tet methylcytosine dioxygenase 2 [TET2], and Fms‐related tyrosine kinase 3 [FLT3]). Results On histochemistry evaluation, the T‐cell population in BM appeared to be preserved in patients who had AML compared with healthy donors. The proportion of T‐regulatory cells (Tregs) in BMAs was higher in patients with AML than in healthy donors. PD1‐positive/OX40‐positive T cells were more frequent in AML BMAs, and a higher frequency of PD1‐positive/cluster of differentiation 8 (CD8)‐positive T cells coexpressed TIM3 or LAG3. PD1‐positive/CD8‐positive T cells were more frequent in BMAs from patients who had multiply relapsed AML than in BMAs from those who had first relapsed or newly diagnosed AML. Blasts in BMAs from patients who had TP53‐mutated AML were more frequently positive for PD‐L1. Conclusions The preserved T‐cell population, the increased frequency of regulatory T cells, and the expression of targetable immune receptors in AML BMAs suggest a role for T‐cell–harnessing therapies in AML., T‐cell subsets are preserved in the bone marrow of patients with acute myeloid leukemia. The expression of targetable immune checkpoints by T cells suggests that therapies harnessing T cells may benefit these patients.

We compared the etiologic organisms of bloodstream infections (BSIs) in cancer patients with central venous catheters (CVCs) between 2 cohorts separated by more than a decade.Gram-negative organisms have become the predominant etiologic organisms of BSIs (52%); they now contribute to 41% of catheter-related BSIs (CRBSIs).Infect Control Hosp Epidemiol 2018;39:727–729

The use of peripherally inserted central catheters (PICCs) has increased over the past few years due to their less serious insertion complications. The purpose of the present study was to determine whether patients receiving PICCs impregnated with minocycline and rifampin had a lower rate of CLABSI compared with a concurrent control group of patients receiving uncoated PICCs.

Background The Centers for Disease Control and Prevention recently introduced the concept of mucosal barrier injury (MBI) in an attempt to recognize the possibility of a gastrointestinal source for certain bloodstream infections. This could underestimate the central venous catheter (CVC) as the source of central line–associated bloodstream infection (CLABSI) in cancer. The definition of catheter-related bloodstream infection (CRBSI) by the Infectious Diseases Society of America is a more specific and stringent definition that identifies the CVC as the source of infection. In our study, we compared the 2 definitions in cancer patients. Methods We retrospectively reviewed 149 CLABSI cases that occurred at our center between January 2013 and March 2014 who had 2 simultaneously positive blood cultures drawn from the CVC and peripheral site or concurrent paired tip and blood cultures. Results Of the 149 patients with CLABSI, only 70 (47%) had definite CRBSI. CRBSI was identified more commonly in non-MBI CLABSI cases than MBI CLABSI (69% vs 18%, P Conclusions The CRBSI definition may be more accurate in identifying the catheter as the source of bloodstream infection in patients with MBI. Because CRBSI continues to occur in patients with MBI, we caution against excluding all MBI patients from CLABSI surveillance.

Mycobacterium arupense is a slow-growing, nonchromogenic, acid-fast bacillus. Its clinical spectrum, epidemiology, and frequency of colonization versus true infection remain unknown. We evaluated the clinical significance of M arupense and positive cultures from cancer patients. We retrospectively reviewed records of all cancer patients treated at our institution between 2007 and 2014 to identify those who had positive cultures for M arupense. Mycobacterium arupense was identified by sequencing the 16S rRNA and hsp65 genes. A total of 53patients had positive cultures, 100% of which were isolated from respiratory specimens. Of these, 7 patients met the American Thoracic Society/Infectious Diseases Society of America criteria for a definitive diagnosis of M arupense infection, 14 cases were considered to be probable infections, and 29 cases were considered to be possible infections. Of the included patients, 13 received therapy for M arupense infection and 40 did not. The outcomes of treated and untreated patients did not differ significantly. No relapses of M arupense infection. In addition, there were no M arupense-related deaths in either group. In cancer patients, M arupense appears to be mostly a commensal organism rather than a pathogen. Patients who did or did not receive treatment had similar outcomes. Validation of these findings in a larger prospective trial is warranted.

Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CL CR ) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CL CR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.)

7016Background: Better defining the immune checkpoint landscape of Acute Myeloid Leukemia will facilitate the rational selection of immune checkpoint targets and combination approaches for future c...

Background The activity levels of telomerase and its mRNA have been found to be more diagnostically sensitive than cytological results in many cancerous tissues and correlate well with the clinical disease stage. Currently, there are several methods of detecting telomerase in tissues and in blood. The most commonly used method is a conventional quantitative real-time polymerase chain reaction (PCR) which is time and labor exhausting. Methods We have developed a simple and innovative blood test method that allows us to diagnose cancer and relapsed cancer in a cost- and time -effective manner. We had evaluated our novel method in two populations: 1) in vivo in three mice with pancreatic ductal adenocarcinoma (PDAC) versus one control mouse and 2) clinically in 30 cancer patients versus 10 individuals without cancer. We compared our novel method with the old conventional method. At least one sample was obtained from each patient included in the study. Results The novel method substantially increased the sensitivity (from 37% to 77%, p