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Background/Objectives: Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; Methods: We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients with steroid-dependent or refractory grade II-IV aGvHD post-alloHSCT. Results: In terms of severe aGvHD, most of the patients (19/28) responded to ECP treatment, while the five-year overall survival (OS) was 34%. After adjustment for several confounder factors, the reduction in immunosuppression (p = 0.026) and number of ECP sessions (p < 0.001) were associated with improved OS. Regarding chronic GvHD, only 19 patients failed to respond to ECP treatment; though significantly lower rates of response were presented in patients with visceral involvement (p = 0.037) and earlier post-transplant GVHD diagnosis (p = 0.001). Over a follow-up period of 45.2 [interquartile range (IQR): 5.6–345.1] months, the 5-year cumulative incidence (CI) of cGvHD-related mortality was 21.2% and was significantly reduced in patients with ECP response (p < 0.001), while the 5-year OS was 65.3%. Conclusions: Our results confirm the safety and efficacy of ECP in patients with GvHD and provide sufficient data for further investigation and the best combination drugs needed such that GvHD will not be the major barrier of allo-HCT in the near future.

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1–43) from initial diagnosis for 32 (6–47) dosages. In the caplacizumab group, a median of 12 (8–23) patients required plasma exchange sessions versus 14 (6–32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6–320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p

Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of this treatment approach. ICANS can have a broad range of clinical manifestations, while various scoring systems have been developed for its grading. Cognitive decline is prevalent in CAR-T therapy recipients including impaired attention, difficulty in item naming, and writing, agraphia, and executive dysfunction. In this review, we aim to present the diagnostic methods and tests that have been used for the recognition of cognitive impairment in these patients. Moreover, up-to-date data about the duration of cognitive impairment symptoms after the infusion are presented. More research on the risk factors, pathogenesis, preventive measures, and therapy of neurocognitive impairment is crucial for better outcomes for our patients.

A crucial complication after allogeneic hematopoietic cell transplantation (alloHCT), namely, acute graft-versus-host disease (aGVHD), occurs in about 50% of transplant recipients, leading to high morbidity and mortality. Thus far, the diagnosis of GVHD has been mainly established through clinical features and histologic or laboratory evidence of periductal lymphocyte infiltration, fibroplasia, and mixed lymphocytic and plasmocytic inflammation. Intensive research is focused on identifying biomarkers for the early diagnosis, prediction of disease, response to treatment, prognosis, and risk stratification of patients. The serum biomolecules that have been investigated are reported and summarized. Moreover, oral tissue involvement in GVHD is described, and other biomarkers that have been proposed, such as saliva, are analyzed. Future research is highlighted as a necessity in order for these biomarkers to be validated and quantified for use in clinical practice.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020–March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 CFB, rs1061170, and rs1065489 CFH in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome.

The analysis of the immunogenetic background of multiple myeloma (MM) has proven key to understanding disease ontogeny. However, limited information is available regarding the immunoglobulin (IG) gene repertoire in MM cases carrying different heavy chain isotypes. Here, we studied the IG gene repertoire in a series of 523 MM patients, of whom 165 and 358 belonged to the IgA and IgG MM groups, respectively. IGHV3 subgroup genes predominated in both groups. However, at the individual gene level, significant (p

All-dielectric metasurfaces offer low material loss and strong field localization and are, therefore, well suited for ultrathin and compact optical devices for electomagnetic wave manipulation at the nanoscale. All-silicon dielectric metasurfaces, in particular, may additionally offer the desired compatibility with complementary metal-oxide semiconductor technology and, hence, are ideal candidates for large-scale monolithic integration on a photonic chip. However, in conventional silicon microfabrication approaches, the combination of mask photolithography with reactive ion etching usually involves expensive masks and multiple preprocessing stages leading to increased cost and fabrication times. In this work, a single-step lithographical approach is proposed for the realization of all-silicon dielectric resonant metasurfaces that involves femtosecond laser processing of silicon below ablation threshold in combination with subsequent wet chemical etching. The method exploits the different etching rate between laser-modified and untreated regions, enabling large-area fabrication of patterned silicon surfaces in a facile and cost-efficient manufacturing approach. It is presented how two-dimensional silicon micro/nanostructures with controllable features, such as nanocones, can be effectively generated and, as a proof of concept, an all-silicon dielectric metasurface device supporting antiferromagnetic order is experimentally demonstrated.

Bone marrow failure (BMF) syndromes are a group of various hematological diseases with cytopenia as a main common characteristic. Given their rarity and continuous progress in the field, we aim to provide data considering the efficiency and safety of the therapeutic methods, focusing on the treatment of aplastic anemia(AA) and paroxysmal nocturnal hemoglobinuria (PNH). We enrolled consecutive patients diagnosed with BMF in two referral centers of Northern Greece from 2008 to 2020. We studied 43 patients with AA (37 adults and 6 children/adolescents) and 6 with classical PNH. Regarding classical PNH, 4 patients have received eculizumab treatment with 1/4 presenting extravascular hemolysis. Among 43 patients with aplastic anemia, PNH clones were detected in 11. Regarding patients that did not receive alloHCT (n=15), 14/15 were treated with ATG and cyclosporine as first line, with the addition of eltrombopag in patients treated after its approval (n=9). With a median follow-up of 16.7 (1.8-56.2) months from diagnosis, 12/14 (85.7%) are alive (4-year OS: 85.1%). AlloHCT was performed in 28 patients. Five patients developed TA-TMA which did not resolve in 3/5 (all with a pre-transplant PNH clone). With the follow-up among survivors reaching 86.3 (6.3-262.4) months, 10-year OS was 56.9%, independently associated with PNH clones after adjusting for age (p=0.024). In conclusion, our real-world experience confirms that novel treatments are changing the field of BMF syndromes. Nevertheless, there is still an unmet need to personalize algorithms in this field.