Circulating bacterial DNA and neutropenic fever during anti-leukaemia chemotherapy.
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ABSTRACT:
SUBMITTER: Rashidi A
PROVIDER: S-EPMC7719597 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse. However, there are few reports of alterations of in adult acute myeloid leukemia (AML) patients. Stool samples of each treatment-naïve AML patient were collected the day before initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. No antimicrobial prophylaxis was in placed in all participants. Ten cases of AML patients (4 male and 6 female) were included with a median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes dominated during the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference +20.2; p < 0.0001) while Escherichia notably declined during the same period (mean difference -11.2; p = 0.0064). At the operational taxonomic unit (OTU) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTU of 203.1 vs. 131.7; p = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease during the febrile neutropenic period. Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow.
| S-EPMC7592783 | biostudies-literature
Project description:Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients. Serial plasma DNAs were collected at diagnosis, after the 1st cycle of NAC and after curative surgery. For the target enrichment, we designed RNA baits covering a total of ?202kb regions of the human genome including a total of 82 cancer-related genes. For ctDNA, 15 serial samples were collected and 87% of plasma SNVs were detected in 13 BC samples that had somatic alterations in tumor tissues. The TP53 mutation was most commonly detected in primary tumor tissues and plasma followed by BRCA1 and BRCA2. At BC diagnosis, the amount of plasma SNVs did not correlate with clinical stage at diagnosis. With respect to the therapeutic effects of NAC, we found two samples in which ctDNA disappeared after the 1st NAC cycle achieved a pathologic complete response (pCR). In addition, the amount of ctDNA correlated with residual cancer volume detected by breast MRI. This targeted ultra-deep sequencing for ctDNA analysis would be useful for monitoring tumor burden and drug resistance. Most of all, we suggest that ctDNA could be the earliest predictor of NAC response.
| S-EPMC5689695 | biostudies-other
Project description:Neutropenic fever (NF) is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial measurements of nine biomarkers [C-reactive protein (CRP), protein C, interleukin (IL)-6, IL-8, IL-10, IL-1?, tumor necrosis factor-?, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793).
| S-EPMC4091290 | biostudies-literature
Project description:ObjectiveTo identify the incidence and clinical course of septic shock combined with neutropenia during chemotherapy in gynecological cancer patients.MethodsWe retrospectively reviewed the medical records of all gynecological cancer patients who received intravenous chemotherapy between March 2009 and March 2018. Patients diagnosed with neutropenic septic shock (NSS) during the course of chemotherapy were identified. We calculated the overall incidence and mortality rate of NSS, and analyzed risk factors and clinical course.ResultsA total of 1,009 patients received 10,239 cycles of chemotherapy during the study period. Among these, 30 (3.0%) patients had 32 NSS events, of which 12 (1.2%) died. With respect to patient age during the first course of chemotherapy, the incidence of NSS after the age of 50 was significantly higher than that in patients under 50 (3.9% vs. 1.4%, p=0.034). As the number of chemotherapy courses increased, the incidence of NSS increased, and linear-by-linear association analysis showed a positive correlation (p=0.004). NSS events occurred on average 7.8 days after the last cycle of chemotherapy, and the median duration of vasopressor administration was 23.3 hours. The median age (64.0 vs. 56.5, p=0.017) and peak heart rate (149.5 min-1 vs. 123.5 min-1, p=0.015) were significantly higher in the group of patients who subsequently died of NSS than in those who survived.ConclusionThe overall incidence of NSS in gynecological cancer patients receiving chemotherapy was 3.0%, which is higher than previously estimated. Peak heart rate during NSS events may be an indicator for predicting survival.
| S-EPMC7440980 | biostudies-literature
Project description:Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (< 1%) at the first evaluation showed significantly better PFS (p < 0.001), and the average VAF change further discriminated the PFS in the patients in partial response (p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.
| S-EPMC8358023 | biostudies-literature
Project description:BackgroundMetastatic colorectal cancer (mCRC) is a heterogenous disease with limited precision medicine and targeted therapy options. Monoclonal antibodies against epidermal growth factor receptor (EGFR) have been a crucial treatment option for mCRC. However, proper biomarkers for predicting therapeutic response remain unknown. As a non-invasive test, circulating tumor DNA (ctDNA) is appropriately positioned to reveal tumor heterogeneity and evolution, as it can be used in real-time genomic profiling. To evaluate the significance of ctDNA in monitoring the dynamic therapeutic response and prognosis of mCRC, we detected the baseline and dynamic changes of ctDNA in mCRC patients receiving anti-EGFR therapies.MethodsA single-center study was conducted retrospectively. Plasma samples from mCRC patients who received anti-EGFR therapies were collected at baseline and continuous treatment points. The ctDNA was extracted and sequenced with a target panel of tumor-related genes via next-generation sequencing (NGS). Clinical information was also collected and analyzed.ResultsWe conducted dynamic sampling of 22 mCRC patients, analyzed 130 plasma samples, obtained a baseline genomic mutation profile of the patients. In total, 54 variations were detected in 22 plasma samples, with a positive rate of 77.3% (17/22). TP53 was the most mutated gene (59.1%, 13/22), followed by APC (18.2%, 4/22). There was a high concordance rate of genomic characteristics between the tumor tissue test by polymerase chain reaction and ctDNA test by NGS. The mutation discrepancy increased with an extended course of treatment. During remission TP53 and APC were the most frequently decreased clonal mutations and KRAS, NRAS, ERBB2 and PIK3CA were the most decreased subclonal mutations. Both mutation types were increased during progression. The ctDNA decreased earlier than did the responses of computed tomography and traditional tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen [CEA]). Lactate dehydrogenase level (P = 0.041), CEA level (P = 0.038), and primary lesion site (P = 0.038) were independent risk factors that influenced overall survival. Moreover, patients with RAS mutations tended to have a worse prognosis (P = 0.072).ConclusionsThis study demonstrates that ctDNA is a promising biomarker for monitoring the dynamic response to treatment and determining the prognosis of mCRC.
| S-EPMC8908369 | biostudies-literature
Project description:By studying differently expressed immune genes with gene expression profiling in immune competent children researchers have been able to distinguish between children with asymptomatic viral infection and those with symptomatic viral infection as well as patients with bacterial infection. In this study we asked if gene expression profiling is feasible as a diagnostic tool in febrile neutropenia. We included children under treatment for a malignancy presenting with febrile neutropenia. Clinical data regarding the infectious episode was prospectively collected and children grouped based on microbiological agent detected into virus, bacteria, co-infection and unknown aetiology. Fourty three episodes had sufficient RNA for RNA-sequencing, 15 with respiratory tract virus, 22 with unknown etiology, 4 with co-infection and 2 with bacteria. No pathogen specific host-innate immune expression profile was seen in the group with virus, bacteria nor unknown aetiology probably due to the low white blood cell account (WBC). In the co-infection group with higher WBC but lower absolute neutrophil count (ANC) compared to the other groups, a downregulated innate response were detected. We conclude that gene expression profiling in children presenting with neutropenic fever is not a feasible diagnostic tool for febrile neutropenia in children with cancer due the low WBC.:
2020-08-26 | GSE152341 | GEO
Project description:Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter's syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring.
| S-EPMC5357854 | biostudies-literature
Project description:[This corrects the article DOI: 10.3389/fonc.2022.830816.].
| S-EPMC9132584 | biostudies-literature
Project description:Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline. Mutant allele frequency at baseline was associated with clinical characteristics. Levels drastically fell after one cycle of NAC, especially in patients whose tumors would go on to have a pathological complete response (pCR), but then rose significantly before surgery in patients with significant residual tumor at surgery (p?=?0.0001). The detection of ctDNA early during treatment and also late at the end of NAC before surgery was strongly predictive of residual tumor at surgery, but its absence was less predictive of pCR, especially when only TP53 variants are considered. ctDNA detection at the end of neoadjuvant chemotherapy indicated significantly worse relapse-free survival (HR?=?0.29 (95% CI 0.08-0.98), p?=?0.046), and overall survival (HR?=?0.27 95% CI 0.075-0.96), p?=?0.043). Hence, individualized multi-variant ctDNA testing during and after NAC prior to surgery has prognostic and predictive value in early TNBC patients.
| S-EPMC7477566 | biostudies-literature