Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with hallmarks of cachexia. Biological samples and clinical data were collected from 30 antibiotic- free AML patients at diagnosis and matched volunteers (1:1) in a multicenter, cross-sectional, prospective study. The composition and functional potential of the fecal microbiota were analyzed using shotgun metagenomics. Fecal, blood, and urinary metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycemic disorders. The composition of the fecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and fecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g., Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.

Invasive Fungal Infections in Children With Acute Myeloid Leukemia: A Single-center Experience Over 19 Years.

OBJECTIVE: Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality in children with acute myeloid leukemia (AML). This study aimed to evaluate the incidence, risk factors, etiology, and outcome of IFIs in children with AML and the effect of mold-active antifungal prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed pediatric patients treated for AML between January 2004 and December 2022. Proven, probable, or possible IFIs were defined using standardized definitions of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) classification published at 2008. RESULTS: A total of 298 febrile neutropenia episodes from 78 patients were evaluated. Proven, probable, and possible IFI rates were 3%, 2.6%, and 9.4%, respectively. Profound neutropenia was detected in 18 (58%) and prolonged neutropenia in 20 (64.5%) of the IFI episodes.. Invasive aspergillosis accounted for the majority of IFI episodes; however, non-albicans Candida spp. were the most isolated pathogens in the proven group. Patients with relapsed AML were particularly at risk for the development of IFI ( P =0.02). A significant decrease in IFI episodes was achieved with mold-active antifungal prophylaxis with voriconazole ( P =0.01, odds ratio: 0.288, %95 CI:0.104-0.797). The overall mortality was 35.8%, and the IFI-attributable mortality rate was 25%. In the multivariate analysis, relapsed disease was the most significant risk factor associated with mortality ( P =0.006, odds ratio:4.745; 95% CI: 1.573-14.316). CONCLUSION: Mold-active prophylaxis reduced the rate of IFIs in this cohort however IFI-related mortality was still high as 25% in pediatric AML patients. Relapsed AML was the most significant risk factor associated with mortality.

Prediction of Bloodstream Infection in Pediatric Acute Leukemia by Microbiota and Volatile Organic Compounds Analysis.

INTRODUCTION: Bloodstream infections (BSIs) cause treatment-related mortality in pediatric acute leukemia. We explored the potential of intestinal microbiota and fecal volatile organic compounds (VOCs) analyses to predict BSI. METHODS: In this case-control study, fecal samples of pediatric acute leukemia patients were collected. Microbiota composition and fecal VOC profiles of BSI cases and matched non-BSI controls were compared. RESULTS: In total, 6 patients were included, of which 1 developed BSI and 1 neutropenic fever. Both showed reduced microbial diversity and stability of Bacteroidetes. In the BSI case, Pantoea was identified 15 days before BSI. Significant differences in fecal VOC profiles were measured between the case and controls. CONCLUSION: Microbiota and fecal VOC could serve as biomarkers to predict BSI in pediatric leukemia.

Invasive aspergillosis in relapsed/refractory acute myeloid leukaemia patients: Results from SEIFEM 2016-B survey.

BACKGROUND: In patients with relapsed/refractory acute myeloid leukaemia (R/R AML) who received salvage chemotherapy, limited and not updated studies explored the incidence of invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP). The aims of this multicentre retrospective 'SEIFEM 2016-B' study were as follows: (1) to evaluate the current rate and the outcome of proven/probable IA and (2) to assess the efficacy of AP, in a large 'real life' series of patient with R/R AML submitted to salvage chemotherapy. RESULTS: Of 2250 R/R AML patients, a total of 74 cases of IA (5.1%) were recorded as follows: 10 (0.7%) proven and 64 (4.3%) probable. Information about AP were available in 73/74 (99%) patients. Fifty-eight (79%) breakthrough infections occurred, mainly during AP with posaconazole [25 (43%)]. The patients who received AP during salvage chemotherapy showed a benefit from antifungal therapy (AT) than patients who did not received AP [43 (86%) vs 7 (14%); p < .033]. In a multivariate analysis, AP and absence of severe mucositis had a significant favourable effect on overall response rate. CONCLUSION: Our data demonstrated that the incidence of IA during the salvage chemotherapy is similar to the past. Nevertheless, the attributable mortality rate (AMR) appears to be lower than that previously reported in R/R AML. Further prospective studies should be performed to confirm our preliminary observation and understand and the why a decreased AMR is reported in this setting of high-risk patients.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Healthcare-associated blood stream infections in hematological patients in Finland during the years 2006-2016.

OBJECTIVES: The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients. METHODS: This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016. RESULTS: The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n = 731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59 years in 2006-2008 to 62 years in 2015-2016 (P < .01). Five percent of S aureus isolates were resistant to methicillin and five percent of Pseudomonas aeruginosa isolates were multidrug-resistant. Four percent of Klebsiella and seven percent of E coli isolates were resistant to ceftazidime. CONCLUSIONS: The proportion of gram-positive bacteria decreased and gram-negative bacteria increased over time. The case fatality rate was low and the median age of patients increased during the study.

Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy.

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.

Antifungal prophylaxis and novel drugs in acute myeloid leukemia: the midostaurin and posaconazole dilemma.

With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug-drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITDmut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease.

An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality.

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum ß-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.

Elevated plasma phage load as a marker for intestinal permeability in leukemic patients.

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman's rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.

Hyperammonemia From Ureaplasma Infection in an Immunocompromised Child.

Idiopathic hyperammonemia is a rare, poorly understood, and often lethal condition that has been described in immunocompromised patients. This report describes an immunocompromised patient with acute myelogenous leukemia who developed persistent hyperammonemia up to 705 µmol/L (normal, 0 to 47 µmol/L) refractory to multiple different therapies. However, after beginning azithromycin and then doxycycline therapy for Ureaplasma species infection, the patient showed immediate and sustained clinical improvement and resolution of ammonia levels. Recognizing disseminated Ureaplasma species infection as a potential cause of idiopathic hyperammonemia, an unexplained, often fatal condition in immunocompromised patients, and empirically treating for this infection could potentially be lifesaving.

Infection at diagnosis-a unique challenge in acute myeloid leukemia treatment in developing world.

PURPOSE: A large number of AML patients present with infection at the time of initial presentation in Indian settings. There is lack of published data on the proportion of patients with infection at initial presentation and its impact on induction mortality. METHODS: A retrospective audit of patients with newly diagnosed AML more than 14 years of age, who underwent standard induction chemotherapy between the periods of January 2011 to December 2018, was done. Infection at presentation if any was documented. Induction mortality was defined as death happening within 28 days of starting induction chemotherapy. RESULTS: Among a total of 315 cases of AML, 96 (30%) patients underwent induction chemotherapy with 7 + 3 regimen. Documented infection at baseline was present in 30 (31%) of patients. Another 10 patients had fever at the time of presentation but without any documented infection focus. Fifteen patients died within 4 weeks of induction amounting to induction mortality of 15.6%. Induction mortality was 28% among patients with infection at baseline compared with 7% without baseline infections (P = 0.01). CONCLUSION: Around 40% of patients had fever at the time of presentation, and 31% had documented infections. Baseline infections led to increase in induction mortality. We would like to propose that infection at baseline is to be considered as one of the potential variables in the predictive scoring system for induction mortality in developing countries.

Successful Outcome of Disseminated Fusarium musae Fungemia with Skin Localization Treated with Liposomal Amphotericin B and Voriconazole in a Patient with Acute Myeloid Leukemia.

Fusarium spp. may cause invasive disseminated infections in immunocompromised patients, associated with significant morbidity and mortality. We describe a case of disseminated fusariosis with fungemia and skin localization caused by Fusarium musae in a patient with acute myeloid leukemia successfully treated using liposomal amphotericin B and voriconazole.

Low Rate of Invasive Fungal Infections During Induction and Consolidation Chemotherapy for Adults with De Novo Acute Myeloid Leukemia Without Anti-mold Prophylaxis: Single-Center 2002-2018 Empirical/Pre-emptive Approach.

Broad-spectrum antifungal prophylaxis is currently considered the standard of care for adults with de novo AML for the prevention of invasive fungal infections (IFIs), especially invasive pulmonary aspergillosis (IPA). Because fluconazole has been used in our center as anti-yeast prophylaxis, we sought to analyze in detail the incidence of IFIs over a 17-year period, as well as their impact on outcome. A standardized protocol of patient management, including serum galactomannan screening and thoracic CT-guided diagnostic-driven antifungal therapy, was used in all patients. A total of 214 consecutive adults with de novo AML who were treated in 3 CETLAM (Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias) protocols from 2002 to 2018 were included. The 90-day incidence of any IFI (including possible cases) was 11% (95% CI 4-15%), most cases occurred during induction chemotherapy (8%, 95% CI 4-12%), and most cases were probable/proven IPA (8%, 95% CI 3-13%). Developing an IFI during induction and consolidation had no impact on 1-year survival. A case-control study with 23 cases of IPA and 69 controls identified induction/re-induction chemotherapy, chronic pulmonary disease and age > 60 years/poor baseline performance status as potential pretreatment risk factors. The current study proves that inpatient induction and consolidation chemotherapy for de novo AML can be given in areas with "a priori" high-burden of airborne molds with fluconazole prophylaxis, while the selective use of anti-mold prophylaxis in patients at very high risk may further reduce the incidence of IFI in this specific clinical scenario.

[Breakthrough of invasive fungal disease with posaconazole as primary prophylaxis after induction chemotherapy for acute myeloid leukemia].

Objective: To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML). Methods: A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared. Results: During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05]. Conclusions: Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

Baseline Chest Computed Tomography for Early Diagnosis of Invasive Pulmonary Aspergillosis in Hemato-oncological Patients: A Prospective Cohort Study.

Invasive pulmonary aspergillosis (IPA) has dire consequences in hemato-oncological patients. We report our experience with performing routine baseline chest computed tomography for early diagnosis of IPA. We found high rates of proven or probable IPA diagnosed on admission among patients with newly diagnosed acute myeloid leukemia.

Comparative outcomes of myeloablative and reduced-intensity conditioning allogeneic hematopoietic cell transplantation for therapy-related acute myeloid leukemia with prior solid tumor: A report from the acute leukemia working party of the European society for blood and bone marrow transplantation.

Therapy-related acute myeloid leukemia (t-AML) arises as a late complication following antecedent solid tumors or hematologic diseases and their associated treatments. There are limited data regarding risk factors and outcomes following allogeneic hematopoietic cell transplantation (HCT) for t-AML following a prior solid tumor, and furthermore, the impact of myeloablative (MAC) vs reduced-intensity conditioning (RIC) on survival is unknown. The acute leukemia working party (ALWP) of the European society for blood and bone marrow transplantation (EBMT) performed a large registry study that included 535 patients with t-AML and prior solid tumor who underwent first MAC or RIC allogeneic HCT from 2000-2016. The primary endpoints of the study were OS and LFS. Patients receiving RIC regimens had an increase in relapse incidence (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.02-2.26; P = 0.04), lower LFS (HR, 1.52; 95% CI 1.12-2.05, P = 0.007), and OS (HR, 1.51; CI 1.09-2.09; P = 0.012). There were no differences in NRM and GRFS. Importantly, LFS and OS were superior in patients receiving ablative regimens due to a decrease in relapse. As NRM continues to decline in the current era, it is conceivable that outcomes of HCT for t-AML with prior solid tumor may be improved by careful patient selection for myeloablative regimens.

Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for patients with acute myeloid leukemia (AML). During transplantation, patients undergo a period of severe neutropenia, which puts them at high risk for infectious complications. However, the impact of patient colonization with multidrug-resistant organisms (MDRO) on overall survival remains unclear. METHODS: In this retrospective, single-center study, the authors analyzed data from 264 patients with AML who underwent a first allo-HSCT between January 2006 and March 2016 at their institution. Primary endpoints were overall survival and nonrelapse-related mortality. RESULTS: One hundred forty-two of 264 patients (53.8%) were colonized by at least 1 MDRO, mainly with vancomycin-resistant Enterococcus faecalis/faecium (n = 122). The characteristics of colonized patients did not differ from those of MDRO-negative patients with respect to median age (53.5 vs 53 years), cytogenetic risk according to European LeukemiaNet criteria, remission status before allo-HSCT (first or second complete remission: 55.7% vs 60.7%, respectively; active disease: 44.4% vs 39.3%, respectively), donor type, or hematopoietic cell transplantation-comorbidity index (HCT-CI). Compared with noncolonized patients, MDRO-positive patients had an inferior probability of survival at 5 years (43.3% vs 65.5%; P = .002), primarily because of a higher cumulative incidence of nonrelapse-related mortality (33.9% vs 9.4%; P < .001). Death caused by infections occurred in 15.5% of colonized patients versus 4.9% of noncolonized patients. There was no difference in the cumulative incidence of relapse in MDRO-positive versus MDRO-negative patients (33.8% vs 42.1%, respectively; P = .798). CONCLUSIONS: The current data emphasize the importance of regular MDRO screenings and prompt further investigations into the impact of colonization with MDRO on the immune system after allo-HSCT. Cancer 2018;124:286-96. © 2017 American Cancer Society.

Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut.

Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.