Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival

Are biological systems poised at criticality?

Many of life's most fascinating phenomena emerge from interactions among many elements--many amino acids determine the structure of a single protein, many genes determine the fate of a cell, many neurons are involved in shaping our thoughts and memories. Physicists have long hoped that these collective behaviors could be described using the ideas and methods of statistical mechanics. In the past few years, new, larger scale experiments have made it possible to construct statistical mechanics models of biological systems directly from real data. We review the surprising successes of this "inverse" approach, using examples form families of proteins, networks of neurons, and flocks of birds. Remarkably, in all these cases the models that emerge from the data are poised at a very special point in their parameter space--a critical point. This suggests there may be some deeper theoretical principle behind the behavior of these diverse systems.Comment: 21 page

Structure and physical properties of the bipolar outflow source NGC 7023

Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

Structure and physical properties of the bipolar outflow source NGC 7023

Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

Adaptive Bandwidth Provisioning with Explicit Respect to QoS Requirements

Abstract. We propose adaptive bandwidth provisioning schemes enabling quality of service (QoS) guarantees. To this end, we exploit periodic measurements and traffic predictions to capture closely traffic dynamics. We make use of the Gaussian traffic model providing available bounds for QoS to derive the associated bandwidth demands. Moreover, special attention is paid for alleviating some typical problems with adaptive provisioning like QoS degradations and signaling overhead. Numerical and simulative investigations using real traffic traces show that the proposed schemes outperform some previous ones

Nano-scale solute heterogeneities in the ultrastrong selectively laser melted carbon-doped CoCrFeMnNi alloy

Rapid melting and solidification cycle during additive manufacturing provides a non-equilibrium environment that generates a large amount of internal defects, including dislocations, precipitations, and solute heterogeneity. These internal defects not only enhance the strength of materials by interacting with mobile dislocations but also reduce ductility due to coherency loss. To minimize the coherency loss from internal defects, defect size control in the additively manufactured products becomes an important issue. In this work, the high strength-ductility combination of additively manufactured carbon-doped CoCrFeMnNi is achieved by designing nano-scale solute heterogeneities in the matrix. The CoCrFe-MnNi solid-liquid two-phase region and interstitial carbon promote Mn and Ni segregation at cell networks and nano-sized precipitations, respectively. Laser scan speed during additive manufacturing determines the solidification rate that controls the solute cell network size. The MnNi co-segregated solute network not only interacts with dislocations but also induces strong back-stress hardening that contributes to achieving similar to 900 MPa yield strength with similar to 30% elongation which combination is significantly larger than the recent additively manufactured high-entropy alloys. This work demonstrates the importance of heterogeneity control in the additively manufactured materials to gain outstanding mechanical properties.11Nsciescopu

Superior tensile properties of 1%C-CoCrFeMnNi high-entropy alloy additively manufactured by selective laser melting

CoCrFeMnNi high-entropy alloys containing 1 at% carbon (C-HEAs) were additively manufactured using selective laser melting (SLM). Superior tensile properties of the as-built C-HEA (to previously reported ones) were achieved by utilizing multiple strengthening mechanisms (i.e. solid solution, grain refinement, dislocation density, and nano-precipitation) by this new manufacturing method. In particular, the SLM process could allow to maximize the strengthening effect of carbon addition to HEAs via finely distributed nano-carbides at the boundaries of solidification cellular structure. This work will open a new window to utilize the SLM process for enhanced mechanical properties of HEAs with great potential. [GRAPHICS] IMPACT STATEMENT CoCrFeMnNi high-entropy alloys containing 1 at% carbon were successfully produced by selective laser melting, and the alloys exhibited much better tensile performance than additive manufactured high-entropy alloy previously reported.11Ysciescopu