scholarly journals Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia

2014 ◽  
Vol 16 (1) ◽  
pp. 83-88 ◽  
Author(s):  
U Schnetzke ◽  
B Spies-Weisshart ◽  
O Yomade ◽  
M Fischer ◽  
T Rachow ◽  
...  
2017 ◽  
Vol 6 (12) ◽  
pp. 2814-2821 ◽  
Author(s):  
Alaa M. Ali ◽  
Daniel Weisel ◽  
Feng Gao ◽  
Geoffrey L. Uy ◽  
Amanda F. Cashen ◽  
...  

2020 ◽  
Vol 99 (11) ◽  
pp. 2547-2553
Author(s):  
Olivier Ballo ◽  
Eva-Maria Kreisel ◽  
Fagr Eladly ◽  
Uta Brunnberg ◽  
Jan Stratmann ◽  
...  

Abstract Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.


2019 ◽  
Vol 71 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Jessica R Galloway-Peña ◽  
Yushu Shi ◽  
Christine B Peterson ◽  
Pranoti Sahasrabhojane ◽  
Vancheswaran Gopalakrishnan ◽  
...  

Abstract Background The majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes in patients with acute myeloid leukemia (AML). Methods 16s rRNA-based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients. Microbiome characteristics were correlated with clinical outcomes both during and after IC completion. Results At the start of IC, higher stool Shannon diversity (hazard ratio [HR], 0.36; 95% confidence interval [CI], .18–.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI, .18–.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cutoff of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum β-lactamase–producing organism. Patients who received carbapenems for >72 hours had significantly lower α-diversity at neutrophil recovery (P = .001) and were approximately 4 times more likely to have infection in the 90 days following neutrophil recovery (HR, 4.55; 95% CI, 1.73–11.93). Conclusions Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that improved targeting of antibiotic administration during IC could decrease subsequent infectious complications in AML patients. Baseline microbiome diversity is a strong independent predictor of infection during acute myeloid leukemia induction chemotherapy (IC) among clinical and microbiome covariates. Higher baseline levels of Porphyromonadaceae appear protective against infection, while carbapenem use is associated with consequences to the microbiome and infection susceptibility post-IC.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 973 ◽  
Author(s):  
Annette K. Brenner ◽  
Øystein Bruserud

Acute myeloid leukemia (AML) is a highly heterogeneous disease with regard to biological characteristics and receptor expression. Toll-like receptors (TLRs) are upstream to the transcription factor NFκB and part of the innate immune system. They are differentially expressed on AML blasts, and during normal hematopoiesis they initiate myeloid differentiation. In this study, we investigated the response upon TLR stimulation in an AML cohort (n = 83) by measuring the increase of NFκB-mediated cytokine secretion. We observed that TLR4 is readily induced in most patients, while TLR1/2 response was more restricted. General response to TLR stimulation correlated with presence of nucleophosmin gene mutations, increased mRNA expression of proteins, which are part of the TLR signaling pathway and reduced expression of transcription-related proteins. Furthermore, signaling via TLR1/2 appeared to be linked with prolonged patient survival. In conclusion, response upon TLR stimulation, and especially TLR1/2 induction, seems to be part of a more favorable phenotype, which also is characterized by higher basal cytokine secretion and a more mature blast population.


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
L. Ballotta ◽  
S. M. Trisolini ◽  
A. P. Iori ◽  
U. La Rocca ◽  
A. Micozzi ◽  
...  

The occurrence of acute myeloid leukemia (AML) within six months from a diagnosis of breast cancer (BC) is rarely reported in the literature, and it is associated with a poor prognosis. We report herein the case of a 40-year-old woman referred to our centre affected by BC and simultaneous AML. The patient proved refractory to first line therapy and achieved complete remission (CR) with a clofarabine-based regimen followed by allogeneic stem cell transplantation (ASCT). Both during salvage chemotherapy and after ASCT, the patient presented severe infectious complications ( acute cholecistytis and Nocardia pneumonia, respectively) treated with surgery, and currently she is alive in CR for both diseases after 29 months of follow-up. The case highlights the importance of a diagnostic assessment of any unexplained cytopenia in association with solid neoplasia under treatment, underlining the feasibility and priority of a timely treatment of the haematological neoplasm in order to achieve long-term survival.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4385-4385 ◽  
Author(s):  
Rajesh Sehgal ◽  
Wassim McHayleh ◽  
James Natale ◽  
Anastasios Raptis ◽  
Mounzer Agha ◽  
...  

Abstract The most effective reinduction regimen for acute myeloid leukemia (AML) patients who do not achieve complete remission (CR) after one cycle of cytarabine combined with an anthracycline is not well established. In an effort to search for new synergistic and non-cross resistant antileukemic regimens different chemotherapeutic combinations have been investigated in refractory AML patients. Multiple regimens including high dose cytarabine, anthracyclines, fludarabine and etoposide have been used with CR rates up to 40%. Mitoxantrone and etoposide have activity in AML as induction agents but their role in reinduction in patients not responding to first line therapy has not been fully established. In the current retrospective study we evaluated the efficacy and toxicity of mitoxantrone and etoposide in AML patients treated at our institution who did not respond to first induction therapy with cytarabine and an anthracycline. A total of fifty seven AML patients were treated with mitoxantrone and etoposide (mean age 55 years, range 18–75 years). Twenty four patients were treated with mitoxantrone 10 mg/m2/d and etoposide 100 mg/m2/d both administered intravenously, days 1 to 5 (regimen 5+5) and thirty three patients were treated with mitoxantrone 10 mg/m2/d administered intravenously days 1 to 3 and etoposide 100 mg/m2/d administered intravenously, days 1 to 5 (regimen 3+5). Twenty six of fifty seven patients (46%) achieved CR. CR was achieved in 38% of patients (9/24) treated with the 5+5 regimen and 52% of patients (17/33) treated with the 3+5 regimen. Mean blast percentage before treatment with mitoxantrone and etoposide was 25% in patients who achieved CR vs 40% in patients who did not achieve CR (p < 0.03). Grade 3/4 hepatic toxicities were seen in 5% (3/57) of patients and there were no grade 3 or 4 renal toxicities. The median duration of neutropenia in patients achieving CR was 29 days after reinduction. 10% (6/57) of the patients died from infectious complications. Cytogenetic analyses were performed prior to first-line therapy in all patients. Patients with favorable cytogenetics treated with etoposide and mitoxantorne had 100% CR (3/3), patients with standard cytogenetics had 58% CR (19/33) and patients with unfavorable cytogenetics had 19% CR (4/21). Overall CR was achieved in 61% (22/36) of patients with favorable and standard cytogenetics. Our data suggest that the combination of etoposide and mitoxantorne is an active and well tolerated regimen, especially in patients with favorable and standard cytogenetics, and warrants further studies in prospective trials.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1011-1011
Author(s):  
Marek Seweryn ◽  
Jerzy Wojnar ◽  
Dariusz Kata ◽  
Slawomira Kyrcz-Krzemien

Abstract Abstract 1011 Poster Board I-33 Background: Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation increases the risk of infectious complications. Material and methods: 118 AML patients, included in two consecutive randomized trials between 1999-2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65 ). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/- purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results: The frequency of neutropenic fever as well as microbiologically documented bacterial, fungal and viral infections during induction and consolidation did not differ between two compared groups - receiving or not purine analogues. Time to infection occurrence and infection duration were similar in both study groups. During induction and both consolidation treatments significant lower values of lymphocytosis were observed in the group of patients treated with purine analogues. There was a slight tendency to increased rate of mucositis for patients treated with purine analogues (60% vs. 44.3%, p=0.07) during induction treatment, while infections affecting skin and soft tissues were significant frequent for patients treated without purine analogues (43.3% vs. 18%, p=0.03) during second consolidation treatment (high dose AraC). The usage of intravenous anti-infectious medications (antibiotics, antifungal, antiviral) and periods of hospitalization did not differ between two groups in this study. Conclusions: We conclude that the use of purine analogues, either cladribine or fludarabine along with conventional induction and consolidation therapy does not aggreviate infectious complications in adults with AML. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4955-4955
Author(s):  
Cristina Calderón ◽  
Jose F Falantes ◽  
Francisco Márquez-Malaver ◽  
Jose González ◽  
Maria Luz Martino ◽  
...  

Abstract Abstract 4955 Introduction Infectious complications are among the most recurrent causes of mortality in patients (pts) with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) undergoing intensive chemotherapy (IC). These pts routinely receive anti-infective prophylaxis (AIP) with flourquinolones and antifungals. 5-azacytidine has recently been incorporated to treatment options for AML and MDS. However, the evidence of the effectiveness of AIP in patients treated with 5 azacytidine (AZA) is limited [1–3]. Objectives To analyze the incidence of episodes of infectious fever (IF), type of microbiological isolation and clinical relevance of infectious complications in AML and MDS pts treated with AZA who did not received prophylaxis. Identification a subgroup of pts who may benefit from AIP in this setting. Material/methods We retrospectively analyzed 48 pts with AML and MDS who received AZA from 2008, with a total of 365 cycles administered. Median age was 68 years (29–83y). Distribution: LMA (n=17) and MDS (n=31). One third of these pts had an absolute neutrophil count (ANC)<0. 5×10e9/L at time of starting AZA. Another 33% of pts had received prior IC, being all refractory to previous treatment. Baseline characteristics in table 1. Results Forty-eight febrile episodes were recorded (13% of IF/cycles of AZA). There was no difference in IF in pts with ANC<0. 5×109/L vs ANC>0. 5×10e9/L (p=0. 53). A total of 17 pts suffered at least one episode of IF (35% of the pts). Hospital admission was required in 14 of these 17 pts with a median time of hospitalization of 14 days (4–80). Mortality attributed to infectious complications ocurred only in 3/48 pts (6%). Twelve microbiological isolations were documented, the most common being: Gram negative bacilli (E Coli=4) and aspergillus reported as probable (n=4) and shown in table 1. Upon comparing pts who received prior IC (n=16; 33%) vs AZA as first line treatment, a higher risk for IF per cycle was observed in first group (18% vs 11. 5%; p=0. 06). Double of these pts developed fever (56% vs 25%; p=0. 03), required more hospital admissions (44% vs 22%; p=0. 21) and had longer duration of hospital stay (22 vs 14 days; p=0. 71). Finally, the group of patients that underwent previous IC, had higher rate of fungal infection by aspergillus and candida (5/9 isolations; 55% vs 0/5; 0%. P <0. 001), although no difference was observed in terms of mortality attributed to infection (6% each group) because of the reduced number of pts who died of this complication overall (3/48). Conclusions To our knowledge, this is the first study to evaluate the frequency and impact of IF in pts treated with AZA not receiving routinely AIP. Overall, the incidence of IF is lower than the reported in similar series. These results allow to identify pts that previously were treated with IC as those at highest risk of fungal infection. Thus, prophylaxis should be considered in this group. Prospective studies are needed to assess the requierement of prophylaxis during treatment with 5 azacytidine. Jain N et al. Benefit of Anti-infectious Prophylaxis in Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome receiving Frontline “Targeted Therapy”. Blood (ASH) 2007, 110:Abstract 2858 Je-Hwan Lee et al. Decreased incidence of febrile episodes with antibiotic prophylaxis in the treatment of decitabine for myelodysplastic syndrome. Leuk Res 35 (2011):499–503 Merkel D et al. Predictive Parameters for Infections During Azacitidine Therapy in High Risk MDS Patients. Blood (ASH) 2011, 118:Abstract 3811 Disclosures: No relevant conflicts of interest to declare.


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