rotl: an R package to interact with the Open Tree of Life data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135519/1/mee312593_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135519/2/mee312593.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135519/3/mee312593-sup-0001-AppendixS1.pd

Systematic Review and Meta-Analysis of Extracorporeal Photopheresis for the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease; Extracorporeal photopheresis; Steroid-refractory diseaseEnfermedad crónica de injerto contra huésped; Fotoféresis extracorpórea; Enfermedad refractaria a esteroidesMalaltia crònica d'empelt contra hoste; Fotofèresi extracorpòria; Malaltia refractaria als esteroidesThe objective of this meta-analysis (MA) was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGvHD). A systematic literature review (SLR) was conducted according to PRISMA guidelines, followed by a feasibility assessment (FA) to assess potential between-study heterogeneity in the meta-analysis (MA). Random-effects MAs were performed for overall survival (OS), failure-free survival (FFS), overall response rate (ORR) and skin-specific response. A subgroup analysis was conducted to explore the effect of NIH assessment criteria. The SLR identified 627 records; 45 unique studies were ultimately included in the MA. For patients treated with ECP, at Month 12, the pooled OS rate was 83.97% and the pooled FFS rate was 60.79%. ORR was 45.34% at Months 3 to 4 and 58.23% at Months 6 to 8. Subgroup analyses showed no significant difference in ORR between studies utilizing NIH criteria and those utilizing non-NIH criteria. Skin-specific response was 34.86% at Months 2 to 3 and 54.22% at Months 4 to 6. There was considerable heterogeneity across all analyses, with I2 values ranging from 65% to 91%. This SLR and MA indicates that ECP results in favorable outcomes in the treatment of SR-cGvHD, including OS, FFS and ORR.This study was funded by Mallinckrodt Pharmaceuticals

Ten Simple Rules for Digital Data Storage

Data is the central currency of science, but the nature of scientific data has changed dramatically with the rapid pace of technology. This change has led to the development of a wide variety of data formats, dataset sizes, data complexity, data use cases, and data sharing practices. Improvements in high throughput DNA sequencing, sustained institutional support for large sensor networks, and sky surveys with large-format digital cameras have created massive quantities of data. At the same time, the combination of increasingly diverse research teams and data aggregation in portals (e.g. for biodiversity data, GBIF or iDigBio) necessitates increased coordination among data collectors and institutions. As a consequence, “data” can now mean anything from petabytes of information stored in professionally-maintained databases, through spreadsheets on a single computer, to hand-written tables in lab notebooks on shelves. All remain important, but data curation practices must continue to keep pace with the changes brought about by new forms and practices of data collection and storage.</jats:p

HLA evolutionary divergence score after donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation.

Donor lymphocyte infusion (DLI) prevents acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapses following hematopoietic stem cell transplantation. Given the life-threatening toxicities such as graft versus host disease (GVHD), the identification of variables associated with response without toxicities is warranted. We hypothesized that HLA evolutionary divergence (HED), defined by the diversity between two given alleles of the same HLA gene, may be such a factor. A retrospective multicenter case-control study was conducted to evaluate the outcomes of pre-emptive (preDLI) and prophylactic DLI (proDLI) regarding their HED score, in AML or MDS patients. DLI-treated patients were matched with controls (1:2 matched) from French transplantation centers according to hospital, hemopathy, donor type, and risk classification. In total, 201 patients were included (N = 147 in the preDLI group, N = 54 in the proDLI group). Relapse-free survival was significantly better in the preDLI group (hazard ratio [HR] = 0.23, 95% confidence interval [CI]: 0.14-0.55, p &lt; 0.001) than in controls. However, this benefit was offset by a higher incidence of severe GVHD (HR = 4.88, 95% CI: 2.30-10.32, p &lt; 0.001). HED A, B, C, DQA1, DQB1, DPB1, and DRB1 were calculated for 65 DLI-treated patients. High-class II HED was significantly associated with higher GVHD and relapse-free survival (GRFS, HR = 0.33, 95% CI: 0.20-0.77, p = 0.005). Specific DQAB associations directly improved GRFS (HR = 0.23, 95% CI: 0.09-0.58, p = 0.004). In conclusion, screening the class II HED score identifies patients eligible for DLI treatment who will benefit the most from this strategy

Molecular characterization of subcutaneous panniculitis-like T-cell lymphoma reveals upregulation of immunosuppression- and autoimmunity-associated genes

Peer reviewe

Elastography improves accuracy of early hepato-biliary complications diagnosis after allogeneic stem cell transplantation

Significant morbidity and mortality have been associated with liver complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Causes and consequences of these hepato-biliary complications are various and might be life-threatening. A high misdiagnosis rate has been reported because of a weak correlation between clinical, laboratory and imaging data. Liver elastography, a liver stiffness measure, is able to assess liver fibrosis and portal hypertension in most liver diseases, but data after allo-HSCT are scarce. Our aim was to determine the interest of sequential liver stiffness measurements for the diagnosis of early hepatic complications after allo-HSCT. Over a two years period of time, 161 consecutive adult patients were included and 146 were analyzed. Ultrasonography and elastography measurements were performed before transplantation, at day+7 and day+14 by three different experienced radiologists unaware of patients'clinical status. Eighty-one (55%) patients had liver involvements within the first 100 days after allo-HSCT. Baseline elastography was not predictive for the occurrence of overall liver abnormalities. A significant increase in 2D real-time shearwave elastography (2D-SWE) was found in patients with sinusoidal obstruction syndrome (SOS). Fifteen patients (10%) fulfilled EBMT score criteria and twelve (8%) reached Baltimore criteria for SOS diagnosis, but only six (4%) had a confirmed SOS. 2D-SWE at day+14 allowed early detection of SOS (AUROC=0.84, p=0.004) and improved sensibility (75%), specificity (99%) and positive predictive value (60%) over the Seattle, Baltimore or EBMT scores. A 2D-SWE measurement above 8.1kPa at day+14 after allo-HSCT seems a promising, non-invasive, and reproducible tool for early and accurate diagnosis of SOS

PD-1 blockade and allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma, a matter of time: a national study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire

Not available

Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party

Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multi-center prospective non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult systemic sclerosis patients undergoing a first autologous hematopoietic stem cell transplantation between December 2012 and February 2016 were prospectively included in the study. Primary endpoint was progression free survival. Secondary endpoints were overall survival, non-relapse mortality, response and incidence of progression. Eighty systemic sclerosis patients were included. Median follow-up duration was 24 (6-57) months after stem cell transplantation using cyclophosphamide plus antithymocyte globulins conditioning for all, with CD34+ selection in 35 patients. At 2 years, progression free survival was 81.8%, overall survival was 90%, response was 88.7% and incidence of progression was 11.9%. The 100 days non-relapse mortality was 6.25% (n=5) with four deaths from cardiac event, including three due to cyclophosphamide toxicity. Modified Rodnan skin score and forced vital capacity improved with time (p24 and older age at transplant were associated with lower progression free survival (Hazard ration 3.32) and 1.77, respectively). CD34+-selection was associated with better response (Hazard ration: 0.46). This study confirms the efficacy of autologous stem cell transplantation in real-life practice for severe systemic sclerosis using non myeloablative conditioning. Careful cardio-pulmonary assessment to identify organ involvement at patient referral, reduced cyclophosphamide doses and CD34+ selection may improve outcomes. The study was registered at ClinicalTrials.gov: NCT0251612

Allogeneic transplantation in acute myelogenous leukemia: a comprehensive single institution's experience

Debates on the role and timing of allogeneic hemtopoietic stem cell transplantation (HSCT) in acute myelogenous leukemia (AML) have persisted for decades. Time to transplant introduces an immortal time and current treatment algorithm mainly relies on the European LeukemiaNet disease risk classification. Previous studies are also limited to age groups, remission status and other ill-defined parameters. We studied all patients at diagnosis irrespective of age and comorbidities to estimate the cumulative incidence and potential benefit or disadvantage of HSCT in a single center. As a time-dependent covariate, HSCT improved overall survival in intermediate- and poor-risk patients (hazard ratio =0.51; P=0.004). In goodrisk patients only eight were transplanted in first complete remission. Overall, the 4-year cumulative incidence of HSCT was only 21.9% but was higher (52.1%) for patients in the first age quartile (16-57 years old) and 26.4% in older patients (57-70 years old) (P<0.001). It was negligible in patients older than 70 years reflecting our own transplant policy but also barriers to transplantation (comorbidities and remission status). However, HSCT patients need to survive, be considered eligible both by the referring and the HSCT physicians and have a suitable donor to get transplantation. We, thus, comprehensively analyzed the complete decision-making and outcome of all our AML patients from diagnosis to last followup to decipher how patient allocation and therapy inform the value of HSCT. The role of HSCT in AML is shifting with broad access to different donors including haploidentical ones. Thus, it may (or may not) lead to increased numbers of allogeneic HSCT in AML in adults

Treatment for First Cytomegalovirus Infection Post–Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir

Background Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir.Methods In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up. The primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). The key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8 through week 16. Treatment-emergent adverse events (TEAEs) were assessed.Results Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of noninferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference: -7.7%; 95% confidence interval [CI]: -14.98, -.36; lower limit of 95% CI of treatment difference exceeded -7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference: 4.4%; 95% CI: -3.91, 12.76). With maribavir (vs valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%).Conclusions Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia. Clinical Trials Registration.NCT02927067 [AURORA].Conclusions Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia. Clinical Trials Registration.NCT02927067 [AURORA].Noninferiority of maribavir to valganciclovir was not met for the primary endpoint of CMV viremia clearance at study week 8. However, maribavir had comparable post-treatment CMV viremia clearance to valganciclovir, and was associated with a lower incidence of treatment-limiting neutropenia.Graphical Abstrac