scholarly journals Clostridioides Difficile Carriage Rate Increases during Pediatric ALL Treatment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1211-1211
Author(s):  
Elizabeth Yang ◽  
Svetlana Rassulova ◽  
Dhwani Sahjwani ◽  
An Harmanli ◽  
Ryan Fassnacht ◽  
...  
Keyword(s):  
High Risk ◽  
16S Rrna ◽  
Carriage Rate ◽  
Clostridioides Difficile ◽  
Microbiome Diversity ◽  
Healthy Siblings ◽  
Pediatric All ◽  
Stool Samples ◽  
Standard Risk ◽  
All Treatment

Abstract Background Clostridioides difficile infection (CDI) is frequent in pediatric patients with acute lymphoblastic leukemia (ALL). Studies have shown upwards of 20% positivity rate in CDI testing among pediatric oncology patients, and up to several percent in pediatric ALL patients in the first 180 days of diagnosis. Antibiotic usage has been variably linked to CDI positivity in these populations. As CDI testing is usually done in symptomatic patients, the question of C. difficile carriage versus CDI has not been addressed. We and others have shown that microbiome is altered in pediatric ALL patients and survivors. We conducted a longitudinal stool microbiome study in pediatric ALL patients and tested the hypothesis that alteration of the microbiome during ALL treatment promotes C. difficile carriage. Methods Children with ALL were prospectively recruited on a rolling basis and stool samples were collected at diagnosis (Dx) and at the end of induction (EOI), consolidation (EOC), interim maintenance I (IMI), delayed intensification (DI), interim maintenance II (IMII), as well as approximately 3 months and 6 months into maintenance (M3, M6). Stool samples from healthy siblings were used as controls. TaqMan-based quantitative-PCR (qPCR) was performed on DNA extracted from stool samples to detect C. diff 16S rRNA, tcdA, (Toxin A) and tcdB (Toxin B) genes . Samples positive or either tcdA or tcdB, or both, were designated positive for toxigenic C. difficile. 16S rRNA hypervariable region V4 was sequenced and analyzed for microbiome diversity and relative abundance of microbiota. Results 32 ALL patients age 3 months-19 years were included. The diagnoses were 12 standard risk and 14 high risk pre-B ALL, 5 T-ALL, and 1 relapsed pre-B ALL. Stool samples were collected from 18 healthy siblings. The numbers of samples tested at each treatment phase were: 29 Dx, 24 EOI, 23 EOC, 25 IMI, 21 DI, 6 IMII, 14 M3, 7 M6. No patient had symptoms suggestive of CDI, and no patient was clinically tested or treated for CDI. Total number of stool samples tested was 149, of which 43 (29%) were positive for toxigenic C. difficile (Figure 1). At diagnosis, 2/29 (7%) patients were positive, compared to 2/18 (11%) in healthy siblings. At EOI, positivity rate increased to 17%, then up to 40% - 52% at EOC, IMI, and DI. C. difficile positivity were lower around 30% at M3 and M6, although few patients reached maintenance to contribute samples for analysis. Twenty-five patients (78%) were positive at some phase. Longitudinal analysis of individual patients showed that C. difficile positivity was intermittent through treatment phases; only 3 patients remained persistently positive. Seven patients (22%) were never positive. Multivariate analysis showed that EOC, IMI, and DI treatment phases were significant risk factors for C. difficile carriage. Neither the number of antibiotics nor the number of antibiotic courses administered was significant. Leukemia risk stratification (high risk versus standard risk) also did not correlate with C. difficile positivity. Microbiome analysis showed statistically significant differences in relative abundance of certain taxa between C. diff positive and negative samples at the class, order, and family levels (Figure 2). Examples include depletion of the class Verrucomicrobiae, which contains protective Akkermansia, and depletion of the common taxa Bifidobacteriaceae and Ruminococcaceae. Conclusion Longitudinal PCR testing of toxigenic C. difficile in pediatric ALL patients demonstrated increased C. difficile prevalence further into treatment phases. C. difficile carriage correlated significantly with depletion of several bacterial taxa, as microbiome diversity decreased overall with successive treatment phases. Our data lend support to the hypothesis that altered microbiome in ALL treatment allows permissibility for C. difficile carriage. In addition, no C. difficile positive patient had symptoms of CDI, therefore, caution must be taken in clinical testing, as there is a high asymptomatic carriage rate. Further longitudinal testing during maintenance and off-therapy is needed to see if C. difficile carriage rate returns to baseline and correlates with recovery of gut microbiome. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gut Microbiota Diversity and Composition Are Altered during Therapy in Pediatric Acute Lymphoblastic Leukemia Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3364-3364
Author(s):  
Elizabeth Yang ◽  
Svetlana Rassulova ◽  
Dhwani Sahjwani ◽  
An Harmanli ◽  
Ryan Fassnacht ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Relative Abundance ◽  
Low Dose ◽  
Lymphoblastic Leukemia ◽  
Healthy Siblings ◽  
Pediatric All ◽  
Stool Samples ◽  
Standard Risk

Abstract Background Childhood acute lymphoblastic leukemia (ALL) has a very high cure rate, however, long-term survivors are at increased risk of chronic medical illnesses that are likely in part microbiome mediated. Previous studies comparing microbiota of pediatric ALL survivors to healthy siblings showed altered composition in survivors. Longitudinal microbiome changes through treatment leading to these alterations are unknown. Methods Children with ALL were enrolled and stool samples were collected at diagnosis and at the end of induction, consolidation, interim maintenance I, delayed intensification, interim maintenance II, as well as approximately 3 months and 6 months into maintenance. Stool samples from healthy siblings were used as controls. Clinical data were collected. DNA was extracted from stool samples and 16S rRNA was sequenced for analysis of hypervariable region V4. Differences in alpha and beta diversities and relative abundance of taxa were calculated between phases and with sibling controls. Results 35 ALL patients age 3 months-19 years were included. The diagnoses were 14 standard risk pre-B ALL, 14 high risk pre-B ALL, 6 T-ALL, and 1 relapsed pre-B ALL. Stool samples were sequenced from 19 healthy siblings. Statistically significant differences in alpha diversity (Shannon) were found between healthy siblings and ALL patients during the more intense chemotherapy phases before low dose maintenance (Figure 1A). Beta diversity (Bray-Curtis), was significantly different between microbiota of ALL patients at diagnosis and their siblings, as well as between ALL patients at diagnosis and at each of the subsequent treatment phases (Figure 1B). Longitudinal comparison using multivariate analysis showed that leukemia risk group (high risk vs standard risk) and antibiotic treatment were significant factors in beta diversity changes. The relative abundance of microbes showed that with treatment, ALL patients exhibit a significant decrease in the phylum Verrucomicrobiota, driven by the genus Akkermansia, which is beneficial to health and is associated with protection against obesity and other chronic inflammatory diseases (Figure 2). Proteobacteria and Fusobacteria, which include proinflammatory species, were increased. Conclusion Pediatric ALL patients have decreased diversity of gut microbes at diagnosis and during treatment. The types of gut microbes harbored in ALL patients are already different than their siblings at diagnosis and continue to change during treatment, but may begin to recover in low dose maintenance therapy. Taxa considered to be beneficial are depleted, while more pathogenic microbes become prominent. Microbiota changes are likely influenced by intensity of chemotherapy and antibiotic exposure. Continued longitudinal follow up is needed to determine whether these changes correlate with adverse long term health outcomes. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Novel Target Genes and Epigenetic Pathways Involved in High Risk Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Sara Deola ◽  
Dhanya Kizhakayil ◽  
Sheanna M Herrera ◽  
Muhammad Elnaggar ◽  
Che-Ann Lachica ◽  
...  
Keyword(s):  
Young Adults ◽  
T Cell ◽  
High Risk ◽  
Linear Regression ◽  
B Cell ◽  
Epigenetic Mechanism ◽  
Cell Phenotype ◽  
Pediatric All ◽  
Standard Risk ◽  
Worse Prognosis

Acute leukemias (AL) is a major cause of cancer death in young age. Extensive research is being conducted to identify novel and innovative approaches for leukemia treatment. Transcriptomic and epigenetic studies might help to discover potential targets, paving the way for molecular-targeted therapies. We analyzed a cohort of 34 AL at diagnosis: 10 pediatric Acute Lymphoblastic Leukemias (8 B-cell, 1 T-cell and 1 bi-phenotypic ALL), 4 young adult ALL (2 B-cell and 2 T-cell phenotype), and 20 pediatric Acute Myeloid Leukemias (AML: 3 M1, 4 M2, 1 M3, 5 M4, 7 M5) with an average blasts population higher than 80% (85+/-11% in ALL; 83+/-13% in AML). Six out of 14 ALL, and 12 out of 20 AML fell under "high risk" category according to clinical standard risk stratification algorithms. On all patients we performed mRNA sequencing (20-million-reads on Illumina Hiseq 4000). Analyses were performed adjusting <0.05 significant p values for multiple testing with the FDR Benjamini-Hochberg procedure. The expression of a set of 800 microRNAs (miRNAs) was evaluated by means of Nanostring miRNA panel. Expression signatures and associations among the different risk groups were calculated with t-tests and linear regression analyses. Applying stringent FDR statistical measurement, we discovered 3 genes that significantly differentiate the transcriptomic profile of high vsintermediate/standard-risk ALL in mRNAseq. The expression of PGR3 (p53 Responsive Gene) and long-non-coding RNAs (lncRNAs) ENSG00000228737 and ENSG00000253174 were respectively 45.5, 4.2 and 3.9 time downregulated in high-risk ALL. To explore more deeply the apoptosis pathway in ALL, we measured Tp53 expression and found it significantly downregulated in the high-risk vsintermediate-standard-risk ALL (p=<0.05, not adj for FDR). Consistently also the linear regression between PGR3 and p53 was significant (p<0.01). No differences in the expression of these genes were detected in AML samples. Tp53 dysregulation is a known hallmark for tumor progression; Tp53 mutations - ranging from 1-2% to 10% in pediatric and adult ALs - correlate with worse prognosis. However, in our cohorts, this gene signature was found significant only in high-risk ALL, homogeneously distinguishing them from intermediate/standard-risk ALL. Transcriptome clinical variant analyses excluded pathogenetic known variants that could explain such marked difference. Also, it is unlikely that somatic genetic mutations acquired by the tumor would explain such a homogeneous behavior of high-risk ALL. Thus, we analyzed the p53 regulatory pathway. Interestingly we found that miRNAs known to be involved in p53 control were significantly upregulated in high-risk vs intermediate-standard-risk ALL (p<0.0404) (Fig.1f-g), suggesting that an epigenetic control is active in high-risk ALL. Also, 2 lncRNAs were highly downregulated in high-risk ALL. Their function is still unknown, but interestingly, one of them ENSG00000253174correlates with GINS4, part of a protein complex implicated in DNA replication and cell proliferation and known to be upregulated in multiple neoplasia like gastric, colon and lung cancer. In our cohorts we found GINS4 significantly downregulated in high-risk vs standard/intermediate-risk ALL (Fig.1d). GINS4 axis is still unknown in AL. We found PRG3 and Tp53 significantly downregulated in high-risk ALL, with PRG3 expression 45 times lower than intermediate/low-risks ALL. Deeper analyses pointed out to an apoptosis control program not generated by a somatic mutation in the tumor, nor a germline clinical patient variant, but by an epigenetic mechanism. We are currently validating these data in a larger cohort, adding also methylome analyses. It will be interesting also to explore the function of the lncRNAs markedly downregulated in our cohort, whose functions are still unknown or partially known. Because of the small numerosity of the ALL high-risk cohort, we were not able to dissect high-risk young adults (4/6) from pediatric ALL (2/6). Although the homogeneity of data suggests a shared apoptosis control mechanism, it will be worthy to explore in a larger cohort whether the general worse prognosis of young adults/adults vs pediatric ALL is at least partially explained by this mechanism. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Strong Prognostic Effect of Concurrent Deletions of IKZF1 and PAX5, CDKN2A, CDKN2B or PAR1 in the Absence of ERG Deletions (IKZF1plus) in Pediatric Acute Lymphoblastic Leukemia Strongly Depends on Minimal Residual Disease Burden after Induction Treatment

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 131-131 ◽  
Author(s):  
Elif Dagdan ◽  
Marketa Zaliova ◽  
Petra Dörge ◽  
Anja Möricke ◽  
Martin Zimmermann ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Factor ◽  
Residual Disease ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Induction Treatment ◽  
Prognostic Effect ◽  
Risk Patients ◽  
Pediatric All ◽  
Standard Risk

Abstract Technical advances in the field of genomic analyses have stimulated a large number of discovery studies on etiological and clinical endpoints in acute lymphoblastic leukemia (ALL) to provide new avenues for preventive strategies, diagnostics and treatment. Recently, deletion of IKZF1 (IKZF1del) was described as a poor prognostic factor in pediatric ALL (Mullighan CG et al., 2012). In our trial AIEOP-BFM ALL 2000 patients with IKZF1del had a lower 5-year event-free survival (EFS; 0.69±0.05 vs. 0.85±0.01; P<0.0001) compared to those without, mainly due to a higher cumulative incidence of relapses (CIR; 0.21±0.04 vs. 0.10±0.01; P=0.001) (Dörge P et al., 2013). IKZF1delwas an independent prognostic factor in this modern protocol. However, on its own, and even in association with minimal residual disease (MRD) levels, its relatively mild prognostic strength limited incorporation in clinical stratification strategies so far. The present study was undertaken to evaluate the prognostic effect of concurrent recurrent genetic aberrations in association with IKZF1del to further refine a high-risk genetic signature for pediatric ALL treated on AIEOP-BFM protocols. For this purpose, we studied a cohort of 1100 German patients with B-cell precursor ALL treated on AIEOP-BFM ALL 2000 with available characterization of genetic aberrations at initial diagnosis by MLPA (MLPA SALSA kit P335; MRC-Holland) and a PCR assay for detection of ERG deletions (ERGdel; Zaliova M et al., 2014). Validation of results was conducted by use of an independent cohort of 417 Italian patients from the same trial. BCR/ABL1-positive patients were excluded from outcome analysis. When single marker analyses were conducted, IKZF1del was the strongest determinator of outcome in the discovery as well as the validation cohort. When IKZF1del was analyzed in combination with PAX5, CDKN2A, CDKN2B, and PAR1 deletions, patients with an additional deletion to that of IKZF1 had the worst EFS and highest CIR in absence of ERGdel and, consequently, were grouped as IKZF1plus (definition: presence of IKZF1del and at least an additional deletion in PAX5, CDKN2A, CDKN2B or PAR1 in the absence of ERGdel). This group comprised 6% of B-lineage ALL patients and had a very poor clinical outcome: 5y-EFS 50%±0.06 compared to 86%±0.01 in IKZF1plus-negatives (p<0.0001); 5y-CIR 45%±0.06 compared to 11%±0.01 (p<0.0001) and was an independent prognostic factor in multivariate analyses including MRD, slow early response, prednisone response, ETV6/RUNX1 status, and WBC (≥100.000/µl) (hazard ratio for an event: 3.39; 95% CI 2.09 – 5.48; p<0.0001). Surprisingly, stratified analysis by MRD demonstrated that the effect of IKZF1plus was restricted to those patients still carrying MRD loads of at least 10E-4 after induction treatment: standard-risk group 5y-EFS 94%±0.06 compared to 38%±0.09 in intermediate-risk and 27%±0.13 in high-risk patients (p<0.0001); standard-risk group 5y-CIR 6%±0.10 compared to 62%±0.10 in intermediate risk and 55%±0.17 in high-risk patients (p<0.0001). Hierarchical clustering of gene expression profiles of IKZF1plus patients did not demonstrate association specific to the different MRD risk groups. Similarly, analysis of whole exome and transcriptome data from material at initial diagnosis in a very restricted number of patients could not demonstrate insights into the observed differences. Newly identified very poor prognostic ALL subgroup – termed IKZF1plus – represented worse outcome compared to that of IKZF1del or others as a sole marker. The differential prognostic effect of IKZF1plus at different MRD levels without currently discernable molecular explanations suggest a quantitative mechanism with higher levels of leukemic cell burden during the early treatment phases predisposing to evolution of a treatment resistant leukemic clone under exposure towards genotoxic chemotherapeutic agents. Potential explanations for these differences in treatment response may be undetected sub-clones already present at diagnosis or underlying germline genetic variation associated with treatment response. Further analyses will be required to better understand this phenomenon. However, due to its strength, the definition of IKZF1plus is likely to aid in the practical implementation of newly detected markers for risk stratification in childhood ALL in a clinical setting. Support: EU FP7 (ENCCA, TRANSCALL), IGA MZ NT/13170-4 Disclosures No relevant conflicts of interest to declare.

Long-Term Outcome of Six Months Maintenance Chemotherapy for ALL in Children: An Extended Follow up Study of TCCSG L92-13

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2262-2262
Author(s):  
Motohiro Kato ◽  
Atsushi Manabe ◽  
Sae Ishimaru ◽  
Daisuke Tomizawa ◽  
Daisuke Hasegawa ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Malignant Neoplasms ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Follow Up Study ◽  
Standard Risk ◽  
All Treatment

Abstract Maintenance therapy is a key component of ALL treatment. Although maintenance with 6-mercaptopurine (6-MP) and methotrexate (MTX) is generally less hemato-toxic, it occasionally causes severe complications such as infections, and too long maintenance is possibly associated with lower adherence. Thus, the duration of maintenance should be as short as possible, but excess shortening of maintenance therapy leads to high relapse incidence, as shown in our previous clinical trial, the Tokyo Children's Cancer Study Group (TCCSG) L92-13 (1992 - 1995, n = 347). In this study, the shortened maintenance therapy to 6 months resulted in EFS of 59.5% at 5.5 years although OS was as good as 81.5%. Especially, higher relapse rate in standard-risk (SR) resulted in EFS of as low as 60.2% (Toyoda Y, et al. J Clin Oncol 2000). However, it should be noted that about 60% of ALL achieved continuous complete remission (CCR) with short maintenance therapy. Thus, to confirm long-term outcome of ALL with this short maintenance therapy, we conducted an extended follow up study of patients enrolled on the TCCSG L92-13. In the L92-13 trial, previously untreated children (15 years or younger) with ALL were enrolled, and were assigned to three risk groups, standard-risk (SR), high-risk (HR) and extremely high-risk (HEX), according to age at diagnosis, immunephenotype, sentinel cytogenetics and initial leukocyte count. All patients received four-drug induction, followed by consolidation therapy including re-induction. Maintenance therapy with daily 6-MP and weekly MTX was shortened to 6 months, and all treatment was discontinued at 12 months after diagnosis. The data was analyzed as of 2014 July. A median of follow up period of this extended study was 14.8 years, and the survival curve is shown in Figure 1A. Relapse was reported in 128 patients, with a median time of relapse was 1.8 years from diagnosis. EFS at 12 years for all patients was 58.7 +- 2.7% (59.2% for SR [n = 127], 57.8% for intermediate-risk [IR, n = 122], and 59.2% for high-risk [HR, n = 101]) and OS was 78.7 +- 2.2% (85.4% for SR, 80.0% for IR, and 69.0% for HR). Incidences of relapse and non-relapse mortality were 37.2 +- 2.6% and 3.2 +- 0.9%, respectively. Five patients (0 in SR group, 3 in HR group, and 2 in HEX group) developed secondary malignant neoplasms before relapse, which resulted in cumulative incidence of secondary malignancy of 0.9 +- 0.5% at 12 years. Patient gender was associated with the outcome, and female had better EFS (65.3 +- 3.7%) compared to male (52.2 +- 3.8%) (p = 0.04, Figure 1B). High-hyperdiploid (HHD) patients had relatively worse prognosis, with EFS of 50.0 +- 11.8%, although it is generally considered as good prognostic factor, and most of the relapsed HHD patients were salvaged and OS was 94.4 +- 5.4%. It is confirmed that 6 months maintenance therapy is insufficient for male, HHD, and standard risk patients. In contrast, most of patients who had been in first CR at previous analysis maintained CCR status. Our results demonstrate that short maintenance therapy can cure a substantial portion of ALL with extremely low non-relapse mortality, and that it may be possible to shorten the duration of maintenance therapy for female and non-HHD patients. This study provides precise information of leukemia biology and highlights the role of maintenance therapy. Ongoing molecular characterization of the cured patients will clarify the subset of patients who can be cured with short maintenance therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Detection of Clostridioides Difficile Toxin B Gene: Benefits of Identifying Gastrointestinal Pathogens by mPCR Assay in the Diagnosis of Diarrhea in Pediatric Patients

2021 ◽  
Author(s):  
Jung-Hyun Byun ◽  
Dongeun Yong ◽  
Heejung Kim
Keyword(s):  
Pediatric Population ◽  
Carriage Rate ◽  
Toxin B ◽  
Clostridioides Difficile ◽  
Gastrointestinal Pathogens ◽  
Gastrointestinal Pathogen ◽  
Positive Rate ◽  
Pediatric Populations ◽  
Stool Samples ◽  
Mpcr Assay

Abstract In the pediatric population, severe Clostridioides difficile infection sometimes occurs, but most cases are asymptomatic. Since the asymptomatic carriage rate is reportedly high in pediatric populations, diagnosis of CDI is difficult. Here, we analyzed 960 results of gastrointestinal pathogen multiplex PCR to estimate the positive rate of toxigenic C. difficile in pediatric populations aged between 0 and 18 years. The overall rate of C. difficile toxin B positivity was 10.1% in the stool samples. The positive rate peaked in 1-year-old infants (29/153, 19.0%), and decreased continually thereafter. The positive rate we observed was lower than the rates described in the literature. Remarkably, no C. difficile was detected in neonates. Antibiotic usage was inversely related to the positive rate, especially in infants < 2 years of age. The odds ratio of antibiotics was 0.44 (95% confidence interval (CI) 0.28–0.68; P < 0.001). The presence of concomitant gastrointestinal pathogens was not associated with toxigenic C. difficile positivity. Even though toxigenic C. difficile infection is neither an important nor a common cause of pediatric diarrhea, children can spread it to adults who are at risk of developing CDI. Pediatric population can act as hidden reservoirs for pathogenic strains in the community.

scholarly journals LINC-28. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH MEDULLOBLASTOMA TREATED AT THE NATIONAL CANCER INSTITUTE (INCA) IN RIO DE JANEIRO, BRAZIL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii383-iii384
Author(s):  
Gabriela Oigman ◽  
Diana Osorio ◽  
Joseph Stanek ◽  
Jonathan Finlay ◽  
Denizar Vianna ◽  
...  
Keyword(s):  
High Risk ◽  
Maternal Education ◽  
Survival Outcomes ◽  
Middle Income ◽  
Female Ratio ◽  
High Risk Patients ◽  
Presenting Symptoms ◽  
Risk Patients ◽  
Epidemiological Characteristics ◽  
Standard Risk

Abstract BACKGROUND Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. Brazil is an upper-middle income country according to World Bank, with features of LMIC and HIC. METHODS We conducted a retrospective review of 126 children (0–18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively; overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS The male/female ratio was 1.42 and the median age at diagnosis was 7.9 years. Headache (79%) and nausea/vomiting (75%) were the most common presenting symptoms. The median time from onset of symptoms to surgery was 50 days. The OS for standard-risk patients was 69% and 53% for high-risk patients. Patients initiating radiation therapy within 42 days after surgery (70.6% versus 59.6% p=0.016) experienced better OS. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.025). Patients who lived &gt;40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS These findings suggest that socioeconomic factors, education, early diagnosis and continuous data collection, besides oncological treatment must be adressed to improve the survival of children with MB.

scholarly journals 789. Evaluation of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S438-S439
Author(s):  
Tanner M Johnson ◽  
Amanda Howard ◽  
Kerry Schwarz ◽  
Lorna Allen ◽  
Misha Huang ◽  
...  
Keyword(s):  
High Risk ◽  
Fecal Microbiota Transplantation ◽  
Therapeutic Option ◽  
Treatment Options ◽  
High Risk Patient ◽  
Recurrent Infection ◽  
Control Group ◽  
Clostridioides Difficile ◽  
All Cause Mortality ◽  
Clostridioides Difficile Infection

Abstract Background Recurrent Clostridioides difficile infection (rCDI) within 180 days of the index episode is associated with a 33% increase in mortality and, to-date, few treatment options exist to prevent recurrent infection. Bezlotoxumab (BEZ) is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in patients at high-risk for recurrence outside of controlled trials. This study aimed to compare BEZ to a historical standard of care (SoC) cohort for the prevention of rCDI in patients at high risk for recurrence. Methods A multi-center retrospective cohort study of patients within an academic health-system with one or more risk factors for rCDI. Patients received SoC with oral vancomycin (VAN) or fidaxomicin (FDX) from January 2015 to December 2017 or BEZ, in addition to oral SoC, from September 2017 to September 2019. The primary outcome was rCDI within 90 days of completion of oral VAN or FDX. Secondary outcomes included all-cause readmission, all-cause mortality, and safety events at 90 days. Results One-hundred twenty patients received BEZ in addition to SoC (n=47) or SoC alone (n=73). Mean (SD) age was 55 (16) years, mean (SD) number of lifetime CDI was 3 (2) episodes, and 30.8% of patients had severe CDI. Six (12.8%) patients in the BEZ cohort and thirty-one (42.5%) in the SoC cohort experienced rCDI at 90 days [OR (95% CI) = 0.20 (0.07-0.53), p=&lt; 0.01]. Incidence of all-cause mortality (2.1% vs 5.5%, p=0.67) and all-cause readmission (42.6% vs 56.2%, p=0.20) within 90 days were not statistically different between groups. Patient body weight, timing of BEZ administration, CDI severity, nor prior receipt of fecal microbiota transplantation significantly affected BEZ effectiveness. BEZ was well tolerated with one infusion-related reaction. There were no heart failure exacerbations among BEZ recipients and two exacerbations identified from control group. Conclusion In patients with at least one risk factor for rCDI, BEZ in addition to SoC was associated with lower rates of recurrent infection than SoC alone and may be a reasonable adjunct therapy in high risk patient populations. Disclosures matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

scholarly journals Awareness of Antimicrobial Stewardship Interventions Within a Community Hospital Network

2020 ◽  
Vol 41 (S1) ◽  
pp. s136-s136
Author(s):  
Cindy Hou ◽  
Nikunj Vyas ◽  
Marianne Kraemer ◽  
David Condoluci
Keyword(s):  
Intensive Care ◽  
High Risk ◽  
Antimicrobial Stewardship ◽  
Wide Distribution ◽  
Frontline Staff ◽  
Clostridioides Difficile ◽  
Days Of Therapy ◽  
Share Data ◽  
Antibiotics Use ◽  
Lack Of Knowledge

Background: A system of 3 community hospitals in New Jersey has actively engaged in antimicrobial stewardship since November 2014. Consultations with infectious diseases specialists are mandatory for patients with sepsis, severe sepsis, septic shock, patients on 3 or more antibiotics, and for those diagnosed with Clostridioides difficile infection (CDI). A multidisciplinary team meets monthly and has begun to improve the appropriateness of antibiotics use and to reduce antibiotic days of therapy per 1,000 patient days. Recently, we participated in a targeted assessment program (TAP) for CDI, and we identified areas of opportunity for antimicrobial stewardship. Methods: The TAP survey was emailed to a wide distribution of employees in the hospital, primarily nurses, physicians, and others with a variable range of experience and for those working in the intensive care units and on the wards. Ultimately, the numbers of responses were 60 in hospital A, 88 in hospital B, and 124 in hospital C. Results: In hospital A, most respondents were nurses or nurse assistants or technicians (63%), and most of the total individuals surveyed worked outside the intensive care unit setting. In hospital B, nurses or nurse assistants or technicians comprised 69% of all responses. Hospital C had the highest percentage of physicians who responded (31%). One theme for all hospitals was that a little more than half of those surveyed felt that for patients with new or recent CDI infections, antibiotics prescribed for infections were reviewed by clinicians. Less than half of respondents believed that education was being given to patients and families about the risks of CDI from antibiotics. With regard to high-risk CDI antibiotics, there was a general lack of knowledge that these were being monitored. For example, survey respondents felt that this was always monitored on clindamycin by only 33% of respondents in hospital A, 40% in hospital B, and 42% in hospital C. With regard to strategies to reduce the unnecessary use of fluoroquinolones, the response of “always” ranged from 35% to 47% of the time. Conclusions: Even though hospitals may have robust antimicrobial stewardship programs, it is important to survey frontline staff. Although all of the antimicrobial stewardship interventions, such as monitoring high-risk-CDI antibiotics, reducing high-risk CDI antibiotics, among others, are performed, there may be lack of knowledge that these initiatives are even being implemented. In this TAP against CDI, we found opportunities to share data with respondents to increase awareness of antimicrobial stewardship to further combat hospital-acquired infections.Funding: NoneDisclosures: None

Healthcare microenvironments define multidrug-resistant organism persistence

2021 ◽  
pp. 1-7
Author(s):  
Brendan J. Kelly ◽  
Selamawit Bekele ◽  
Sean Loughrey ◽  
Elizabeth Huang ◽  
Pam Tolomeo ◽  
...  
Keyword(s):  
16S Rrna ◽  
Hot Spots ◽  
Multidrug Resistant ◽  
Systematic Sampling ◽  
Resistant Organism ◽  
Rrna Gene ◽  
Environmental Cleaning ◽  
Healthcare Environment ◽  
Clostridioides Difficile ◽  
Modifiable Factors

Abstract Background: Multidrug-resistant organisms (MDROs) colonizing the healthcare environment have been shown to contribute to risk for healthcare-associated infections (HAIs), with adverse effects on patient morbidity and mortality. We sought to determine how bacterial contamination and persistent MDRO colonization of the healthcare environment are related to the position of patients and wastewater sites. Methods: We performed a prospective cohort study, enrolling 51 hospital rooms at the time of admitting a patient with an eligible MDRO in the prior 30 days. We performed systematic sampling and MDRO culture of rooms, as well as 16S rRNA sequencing to define the environmental microbiome in a subset of samples. Results: The probability of detecting resistant gram-negative organisms, including Enterobacterales, Acinetobacter spp, and Pseudomonas spp, increased with distance from the patient. In contrast, Clostridioides difficile and methicillin-resistant Staphylococcus aureus were more likely to be detected close to the patient. Resistant Pseudomonas spp and S. aureus were enriched in these hot spots despite broad deposition of 16S rRNA gene sequences assigned to the same genera, suggesting modifiable factors that permit the persistence of these MDROs. Conclusions: MDRO hot spots can be defined by distance from the patient and from wastewater reservoirs. Evaluating how MDROs are enriched relative to bacterial DNA deposition helps to identify healthcare micro-environments and suggests how targeted environmental cleaning or design approaches could prevent MDRO persistence and reduce infection risk.

scholarly journals A phase 2 study of ATRA, arsenic trioxide, and gemtuzumab ozogamicin in patients with high-risk APL (SWOG 0535)

2020 ◽  
Vol 4 (8) ◽  
pp. 1683-1689 ◽  
Author(s):  
Jeffrey E. Lancet ◽  
Anna B. Moseley ◽  
Steven E. Coutre ◽  
Daniel J. DeAngelo ◽  
Megan Othus ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Complete Response ◽  
Gemtuzumab Ozogamicin ◽  
Research Network ◽  
Induction Phase ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Standard Risk

Abstract High-risk acute promyelocytic leukemia (APL) remains a therapeutic challenge, with higher associated rates of early mortality and relapse than standard-risk APL. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) is a well-established treatment for patients with standard-risk APL, but it is not well defined for those with high-risk APL. In a prior study of patients with high-risk APL, the addition of gemtuzumab ozogamicin (GO) to ATO plus ATRA suggested benefit. The SWOG Cancer Research Network conducted a phase 2 study to confirm the efficacy and safety of the combination of ATRA plus ATO plus GO in treating high-risk APL patients. The primary end points were 3-year event-free survival (EFS) and early (6-week) death rates associated with this combination. Seventy patients were treated. With a median follow-up of 3.4 years, the 3-year EFS and overall survival estimates were 78% (95% confidence interval [CI], 67%-86%) and 86% (95% CI, 75%-92%), respectively. Overall, 86% of patients achieved complete response. The 6-week mortality rate was 11%. The most common treatment-emergent toxicities during the induction phase included febrile neutropenia, aspartate aminotransferase/alanine aminotransferase elevation, hyperglycemia, hypoxia, headache, and prolonged QT interval corrected for heart rate. Retinoic acid syndrome occurred in 9% of patients. Approximately 37% of patients did not complete all planned courses of postremission therapy. The combination of ATRA plus ATO plus GO in high-risk APL patients was effective and generally well tolerated, suggesting an opportunity to offer a chemotherapy-free induction platform for patients with this disease. This trial was registered at www.clinicaltrials.gov as #NCT00551460.

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