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33 result(s) for "Mielcarek, Marco"
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Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs Host Disease After Hematopoietic Cell Transplantation
Graft-versus-host disease (GVHD) is common after allogeneic hematopoietic cell transplantation (HCT). Risk for death from GVHD has been associated with low bacterial diversity in the stool microbiota early after transplant; however, the specific species associated with GVHD risk remain poorly defined. We prospectively collected serial weekly stool samples from 66 patients who underwent HCT, starting pre-transplantation and continuing weekly until 100 days post-transplant, a total of 694 observations in HCT recipients. We used 16S rRNA gene polymerase chain reaction with degenerate primers, followed by high-throughput sequencing to assess the relative abundance of sequence reads from bacterial taxa in stool samples over time. The gut microbiota was highly dynamic in HCT recipients, with loss and appearance of taxa common on short time scales. As in prior studies, GVHD was associated with lower alpha diversity of the stool microbiota. At neutrophil recovery post-HCT, the presence of oral Actinobacteria and oral Firmicutes in stool was positively correlated with subsequent GVHD; Lachnospiraceae were negatively correlated. A gradient of bacterial species (difference of the sum of the relative abundance of positive correlates minus the sum of the relative abundance of negative correlates) was most predictive (receiver operator characteristic area under the curve of 0.83) of subsequent severe acute GVHD. The stool microbiota around the time of neutrophil recovery post-HCT is predictive of subsequent development of severe acute GVHD in this study.
Limited yield of SARS-CoV-2 screening in asymptomatic hematopoietic cell transplant and chimeric antigen receptor T-cell therapy patients
Early in the COVID-19 pandemic, screening was initiated in several settings to mitigate asymptomatic transmission of SARS-CoV-2. However, this practice was later discouraged by the Society for Healthcare Epidemiology of America. This single-center retrospective study demonstrates limited utility of SARS-CoV-2 screening tests in asymptomatic HCT and CAR T-cell patients.
Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia
Measurable (‘minimal’) residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before ( n =63) or after ( n =16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD neg /MRD neg patients had excellent outcomes, whereas both MRD neg /MRD pos patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD pos patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.
Cord-Blood Transplantation in Patients with Minimal Residual Disease
Patients with minimal residual disease who received a cord-blood transplant had a higher probability of survival than those receiving a transplant from mismatched unrelated donors and a lower risk of relapse than those receiving a transplant from matched or mismatched unrelated donors. The preferred donor for patients who are in need of an allogeneic hematopoietic-cell transplant remains an HLA-identical sibling. Such a donor is not available for the majority (approximately 70%) of patients, and alternative donor sources are necessary. 1 At the Fred Hutchinson Cancer Research Center, the first alternative choice for patients who do not have an HLA-identical sibling has been an unrelated donor who has been matched with the patient at the allele level for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 (a so-called 10/10 match, or an HLA-matched unrelated donor). However, approximately 50% of white patients who do not have an . . .
Ruxolitinib therapy appears safe prior to allogeneic HSCT for myelofibrosis
Ruxolitinib treatment prior to allogeneic hematopoietic stem cell transplant appeared safe and aided in the prevention of cytokine release syndrome among patients with myelofibrosis, according to results of a phase 2 prospective study. \"[The implications of the study] will let us know if patients with myelofibrosis who take ruxolitinib prior to undergoing stem cell transplant have better posttransplant outcomes,\" Rachel B. Salit, MD, assistant member in the clinical research division at Fred Hutchinson Cancer Research Center and physician at Seattle Care Cancer Alliance, told HemOnc Today. Allogeneic HSCT is the only potential cure for myelofibrosis; however, guidelines suggest the risk for transplant-related complications are acceptable only for transplant-eligible patients with intermediate-2 or high-risk disease based on the dynamic international predictive scoring system.
Diverse gut microbiota may improve OS in allogeneic HSCT
BMT Tandem Meetings feb. 21-25 salt lake city Diversity of gut microbiota at the time of neutrophil engraftment in allogeneic hematopoietic stem cell transplantation appeared associated with OS, according to results of an international multicenter cohort study. Peled and colleagues compared microbiota diversity among patients who underwent allogeneic HSCT at Memorial Sloan Kettering, Duke University Medical Center and University of Regensburg in Germany. \"Recovery from microbiota injury occurs gradually, with diversity increasing but often to a configuration distinct from the pretransplant state.\" - by Melinda Stevens ? PERSPECTIVE Over the past several years, there has been mounting scientific evidence that loss of diversity of bacterial communities in the gastrointestinal tract is associated with worse outcomes after allogeneic hematopoietic cell transplantation.
Diverse gut microbiota may protect gastrointestinal tract in acute GVHD
High diversity of gut microbiota and certain bacterial commensals within Clostridiales order are known to be associated with decreased GVHDrelated mortality after allogeneic hematopoietic stem cell transplantation. Because the majority of intestinal microbiota biomass resides within the colon, Ponce and colleagues hypothesized that certain features of the microbiota offer local protection of the lower gastrointestinal tract. When researchers grouped samples into preonset (day -19 to 0) and postonset (day 1-20) categories via the Mann-Whitney U test, the microbial diversity in lower gastrointestinal cases (median, 2.05) appeared significantly lower than upper gastrointestinal (median, 2.65) and nongastrointestinal group (median, 3.45) prior to acute GVHD onset (P < .05). In a study that included 286 allograft recipients and by evaluating serial stool samples for changes in microbial diversity over time, they found that patients who had lower gut (colonic) acute GVHD had lower microbial diversity than those with upper gut GVHD (with or without lower gut involvement), and those with no GVHD.
Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation
Abstract Background Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. Methods Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. Results Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0). Conclusions High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients. High rates of discordance in PCR results between the upper versus lower respiratory tracts occur for certain respiratory viruses in hematopoietic stem cell transplant patients.