Supplementary Material for: Extracorporeal Photopheresis: An Efficacious and Well-Tolerated Treatment for Cutaneous and Oral Mucosal Chronic Graft-versus-Host Disease

<b><i>Background:</i></b> Extracorporeal photopheresis (ECP) is a second-line therapy for steroid-refractory chronic graft-versus-host disease (cGVHD). <b><i>Objective:</i></b> We describe the long-term efficacy and tolerability of ECP according to the cutaneous phenotype of cGVHD and report on the reduced need for immunosuppressant drugs in this setting. <b><i>Patients and Methods:</i></b> Fourteen patients (8 females) with cutaneous and/or mucosal cGVHD, treated with ECP between October 2010 and May 2016 within a single center, were included. Final analyses included patients who had received ECP for at least 12 months. We prospectively evaluated the efficacy of ECP using lesion-specific clinical scores and by recording changed doses of systemic immunosuppressants. <b><i>Results:</i></b> Of the 14 patients, sclerotic skin lesions were present in 10 (71%). The mRODNAN score decreased in all patients from month 9 onwards, with 40 and 77% reductions at 12 and 36 months, respectively. Six patients (43%) presented with cutaneous lichenoid lesions: this score was reduced in all patients by month 3, reaching a 93% reduction by month 12. Five patients (36%) experienced oral mucosal lichenoid lesions: these scores were decreased by 55% at month 12 and by 100% by month 33. The use of systemic immunosuppressants was reduced in all patients; 4 patients could stop all immunosuppressant drugs after 2 years. ECP was stopped in 3 patients after a complete response. No major ECP-associated adverse effects were observed. <b><i>Discussion and Conclusion:</i></b> ECP was an effective long-term therapy for oral and cutaneous cGVHD: consequently, dose levels of therapeutic immunosuppression could be reduced

Pressure-induced amorphization and polyamorphism: Inorganic and biochemical systems

Pressure-induced amorphization (PIA) is a phenomenon that involves an abrupt transition between a crystalline material and an amorphous solid through application of pressure at temperatures well below the melting point or glass transition range. Amorphous states can be produced by PIA for substances that do not normally form glasses by thermal quenching. It was first reported for ice Ih in 1984 following prediction of a metastable melting event associated with the negative initial melting slope observed for that material. The unusual phenomenon attracted intense interest and by the early 1990s PIA had been reported to occur among a wide range of elements and compounds. However, with the advent of powerful experimental techniques including high resolution synchrotron X-ray and neutron scattering combined with more precise control over the pressurization environment, closer examination showed that some of the effects previously reported as PIA were likely due to formation of nanocrystals, or even that PIA was completely bypassed during examination of single crystals or materials treated under more hydrostatic compression conditions. Now it is important to understand these results together with related discussions of polyamorphic behavior to gain better understanding and control over these metastable transformations occurring in the low temperature range where structural relaxation and equilibration processes are severely constrained. The results will lead to useful new high-density amorphous materials or nanocrystalline composites containing metastable crystalline varieties and the experiments have driven new theoretical approaches to modeling the phenomena. Here we review the incidence and current understanding of PIA along with related phenomena of density- and entropy-driven liquid–liquid phase transitions (LLPT) and polyamorphism. We extend the discussion to include polymeric macromolecules and biologically-related materials, where the phenomena can be correlated with reversible vs irreversible unfolding and other metastable structural transformations