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Key Points Ofatumumab with glucocorticoid therapy for cGVHD resulted in 62.5% ORR at 6 months and 53% FFS at 12 months.Safety was observed with ofatumumab plus glucocorticoid for initial therapy., Visual Abstract, Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01680965.

Los acelerogramas adoptados para realizar estudios de fragilidad en puentes a través de análisis dinámico no lineal son uno de los componentes de mayor influencia en los resultados obtenidos. El objetivo de este trabajo es presentar una metodología para selección y escalado de acelerogramas reales de sismos registrados en distintas partes del mundo en ambientes tectónicos semejantes a los del centro-oeste argentino, de manera tal de contar con series de registros compatibles con espectros para distintas clases de sitio, zonas de peligrosidad sísmica y niveles de amenaza sísmica. Para ello, se hizo uso de la aplicación web de la base de datos de movimientos sísmicos del PEER (Pacific Earthquake Engineering Research Center’s). Se tomaron en consideración los espectros objetivos y distintos parámetros, tales como: magnitud del sismo, tipo de falla, distancia de la estructura a la falla, velocidad media de la onda de corte en los 30 metros superiores del terreno, etc. Mediante la aplicación de un criterio novedoso, en el cual se contempla la Intensidad de Aceleración Espectral (ASI), se arribó a 16 series de sismos considerando: 4 clases de sitio, zonas de elevada y muy peligrosidad sísmica del territorio nacional y periodos de recurrencia de 500 y 2500 años. Estas series de registros representativas de la sismicidad de la región referida podrán utilizarse luego para obtener curvas de fragilidad de mayor confiabilidad para distintas clases de puentes típicos.

Post-transplantation cyclophosphamide (PTCy) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (allo-HCT) across various donor types. However, immune reconstitution and infection incidence after PTCy-based versus conventional GVHD prophylaxis has not been well studied. We evaluated the infection density and immune reconstitution (ie, absolute CD4+ T cell, CD8+ T cell, natural killer cell, and B cell counts) at 3 months, 6 months, and 1 year post-HCT in 583 consecutive adult patients undergoing allo-HCT with myeloablative (n = 223) or reduced-intensity (n = 360) conditioning between 2012 and 2018. Haploidentical (haplo; n = 75) and 8/8 HLA-matched unrelated (MUD; n = 08) donor types were included. GVHD prophylaxis was PTCy-based in all haplo (n = 75) and in 38 MUD allo-HCT recipients, whereas tacrolimus/methotrexate (Tac/MTX) was used in 89 and Tac/Sirolimus (Tac/Sir) was used in 381 MUD allo-HCT recipients. Clinical outcomes, including infections, nonrelapse mortality (NRM), relapse, and overall survival (OS), were compared across the 4 treatment groups. The recovery of absolute total CD4+ T-cell count was significantly lower in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups throughout 1 year post-allo-HCT (P = .025). In contrast, CD19+ B-cell counts at 6 months and thereafter were higher in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups (P

Analysis of the current state of nutrient stocks, flows, and balances of a territory is necessary to inform strategies that can transition the agri-food sector to a circular economy model. In this study, we quantified the nitrogen and phosphorus budgets for the Bolivian agri-food system at national and regional scales by way of agro-ecological zoning. We performed nutrient balances to calculate indicators for sufficiency (extent of nutrient deficit/surplus) and circularity (proportion of nutrients recirculated). We also evaluated the potential of renewable stocks (human excreta and livestock manure) to meet nutrient deficits in the system. Our results showed that there are apparent deficits of 32 kt N and 8 kt P in the system that cannot be accounted for using available data. We estimate the real deficits required to bring yields of 45 crops grown in Bolivia to parity with those of neighbouring countries to be 110 kt N and 33 kt P. About 44% of nitrogen and 74% of phosphorus is currently recirculated in the system, with the major nutrient inputs being biological nitrogen fixation, livestock manure, and crop residues. However, nutrient recycling is likely to decrease in the future because the national strategy to address nutrient deficits is to increase domestic production of synthetic fertilisers. Our analysis also shows that there is a sufficient stock of nutrients already available in human excreta (39 kt N and 5 kt P) to cover 100% of the nitrogen deficit and 64% of the phosphorus deficit. The low-altitude zone of Chiquitania-Pantanal alone accounts for 65% of cultivation and 80% of the nutrient demand in the country. Here, export-oriented crops like soybean and sorghum are grown, but less than 25% of the nitrogen is recirculated. In contrast, there are nutrient surpluses of 41 kt N and 34 kt P in agro-ecological zones like the Valleys and Altiplano where traditional agriculture is practiced, and the majority of food is grown for local consumption. Overall, we find that recycling of human excreta, combined with transfer of regional nutrient surpluses, could be an effective strategy to reduce the overall nutrient deficit in the system.

Advanced instrumentation and modern analysis tools such as transmission electron microscopy (TEM) have led to phenomenal progress in understanding crystallization, in particular from solution, which is a prerequisite for the design-based preparation of a target crystal. Nevertheless, little has been understood about the crystallization pathway under high-temperature annealing (HTA) conditions. Metal oxide crystals are prominent materials that are usually obtained via HTA. Despite the widespread application of hydro-/solvothermal methods on the laboratory scale, HTA is the preferred method in many industries for the mass production of metal oxide crystals. However, poor control over the morphology and grain sizes of these crystals under extreme HTA conditions limits their applications. Here, applying ex-situ TEM, the transformation of a single amorphous spherical submicrometer precursor particle of SrAl

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by a reciprocal translocation between the long arms of chromosomes 9 and 22 that results in expression of the oncoprotein BCR-ABL1. An optimal response to tyrosine kinase inhibitors (TKIs) requires a BCR-ABL transcript level ≤ 10% at 3 months, ≤ 1% at 6 months, ≤ 0.1% at 1 year, and ≤ 0.01% onwards. Complex scenarios like P190 BCR-ABL CML, unusual BCR-ABL transcripts, primary refractory CML, and detection of TKI-resistance mutations during treatment frequently pose a therapeutic challenge. In this article we present some of these clinical scenarios using a case-based approach. J Med Cases. 2020;11(7):215-220 doi: https://doi.org/10.14740/jmc3510

Introduction: new technologies favor the scientific and technical development of society, which is why these must be assimilated into the teaching-learning process by nursing care students. Objective: to characterize the use of information and communication technologies by students of the Degree in Nursing at Pinar del Río University of Medical Sciences between January and March 2018. Methods: observational, descriptive, and cross-sectional study of second-academic year students of bachelor degree in nursing care. Theoretical and empirical methods were used. Statistical measures were applied as absolute frequency and relative percentage. Results: it was found that 23.5 % did not have access to any personal computers. Half of the target group said they own a mobile phone with Android or iOS operating system; 59.3 % of the students did not use the institutional Internet network, 23.5 % used it for teaching purposes; 76.5 % reported using lectures and complementary computerized materials for the individual study; 46. 9% used both computers and conventional aids; 12 % of the students expressed they do not find computer-aided learning useful. Conclusions: it was found the application of Information and Communication Technologies in the teaching-learning process is very useful, having a high access; where Smartphone is the most used; there is a poor use of Internet network for the teaching-learning and research processes. Computer-aided learning is widely used to the individual study.

Post-transplantation cyclophosphamide (PTCy) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (allo-HCT) across various donor types. However, immune reconstitution and infection incidence after PTCy-based versus conventional GVHD prophylaxis has not been well studied. We evaluated the infection density and immune reconstitution (ie, absolute CD4

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL). Both total body irradiation (TBI)-based and chemotherapy only-based myeloablative transplantation conditioning regimens have been applied, but the optimal regimen remains unclear. We performed a systematic review to assess the efficacy of TBI-based versus chemotherapy only-based myeloablative conditioning regimens. We searched PubMed, Embase, and Cochrane databases and meeting abstracts for all studies comparing TBI-based and chemotherapy only-based conditioning regimens in patients who underwent allo-HCT for ALL. Two authors independently reviewed all studies for inclusion and extracted data related to overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), relapse, and acute and chronic graft-versus-host disease (GVHD). Eight studies were included in the final analysis. The overall methodological quality of the included studies was optimal. TBI-based regimens showed evidence of benefit compared with chemotherapy only-based conditioning regimens in terms of relapse (relative risk [RR], 0.82; 95% confidence interval [CI], 0.72 to 0.94; 6 studies, 5091 patients), OS (hazard ratio [HR], 0.76; 95% CI, 0.64 to 0.89; 7 studies, 4727 patients), and PFS (HR, 0.74; 95% CI, 0.63 to 0.85; 7 studies, 4727 patients). The TBI-based regimen did not increase the likelihood of grade II-IV acute GVHD (RR, 1.12; 95% CI, 0.92 to 1.36; 5 studies, 4996 patients) or chronic GVHD (RR, 1.10; 95% CI, 1.00 to 1.21; 5 studies, 4490 patients), or NRM (RR, 0.94; 95% CI, 0.69 to 1.28; 6 studies, 4522 patients). However, TBI-based regimens were associated with an increased risk of grade III-IV acute GVHD (RR, 1.29; 95% CI, 1.01 to 1.63; 3 studies, 3675 patients). A subgroup comparison of patients age ≥16 years showed similar results. This systematic review represents evidence supporting the use of TBI-based conditioning regimen in patients undergoing allo-HCT for ALL who are candidates for myeloablative conditioning, as it offers better OS, PFS, and less relapse with acceptable NRM.

Hematotoxicity represents a frequent chimeric antigen receptor (CAR) T-cell–related adverse event and remains poorly understood. In this multicenter analysis, we studied patterns of hematopoietic reconstitution and evaluated potential predictive markers in 258 patients receiving axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for relapsed/refractory large B-cell lymphoma. We observed profound (absolute neutrophil count [ANC]

Introduction: Between 50-80% of patients with diffuse large B-cell lymphoma (DLBCL) are cured by frontline (1L) R-CHOP immunochemotherapy. Ultra-high risk (UHR) features for poor overall survival (OS) include: progression through the frontline therapy (primary progression, PP), presence of a MYC translocation (MYC-R+), and a high or high-intermediate National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) (Costa, Am. J. Hematol., 2017). We aim to explore the role of these UHR factors in the outcomes of DLBCL patients receiving standard of care (SOC) anti-CD19 CAR T-cell therapy. Methods: This is a retrospective single-center study of relapsed/refractory (R/R) DLBCL patients treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) as SOC at Moffitt Cancer Center according to the FDA label as of March 2021, or who were treated on the expanded access programs (EAP) for axi-cel (NCT03153462) and tisa-cel (NCT03601442) for the provision of CAR T when products fell outside of manufacturing specifications (OOS). We excluded patients who had received prior therapy for indolent B-cell lymphomas (iNHL). We defined patients with primary treatment failure (PTF) as: PP, residual disease after 1L therapy (RD), or early relapse within 6 months of 1L therapy (ER). For patients with PTF, we calculated the number of UHR features (0 to 3): MYC status, NCCN-IPI, and PP. Kaplan-Meier survival curves were used to compare progression free survival (PFS) and overall survival (OS) starting from the date of CAR T-cell infusion, with statistical significance determined using the log-rank test at the P Results: A total of 187 R/R DLBCL patients received SOC or EAP CAR T-cell therapy, of which 116 had DLBCL with no prior therapy for iNHL and were included in this analysis. PTF occurred in 75 patients (65%), of which 30 (40%) patients had primary progression as the failure pattern, 23 (30.7%) patients had MYC-R detected by FISH, and 37 (49.3%) patients had intermediate-high/high NCCN-IPI scores at the time of PTF. The median follow up was 10.05 months. Of the 75 patients with PTF, 69 received axi-cel and 6 received tisa-cel. Main 1L therapies were R-CHOP in 59 (78.6%) cases and DA-EPOCH-R in 14 (18.7%). The median lines of therapy prior to CAR T-cell therapy was 3 (range 2-6 lines). The number of UHR features was associated with a shorter OS after CAR T-cell therapy. The OS for patients with 2-3 and 0-1 UHR were 5.3 months (95% CI, 3.7 to 15.13 months) and not reached, respectively (P=0.005; Figure 1A). In terms of PTF patterns, PP was associated with worse PFS and OS after CAR T-cell therapy compared to other patterns (RD/ER) (PP, mPFS 3.1 months vs RD/ER, mPFS not reached; p Conclusion: Patients with DLBCL who experience PP to frontline immunochemotherapy had shorter PFS and OS after subsequent CAR T-cell therapy compared to other PTF patterns. R/R DLBCL patients with PP represent a poor prognosis subgroup, even with CAR T-cell therapy. It will be important to determine if patients with primary progression have increased benefit from CAR T-cell therapy if it is provided at first relapse rather than after 2 or more prior lines of therapy. Our study suggests that mechanisms of tumor resistance to CAR T-cell therapy may be present in some patients from the time of upfront therapy. Figure 1 Figure 1. Disclosures Chavez: AstraZeneca: Research Funding; Merk: Research Funding; ADC Therapeutics: Consultancy, Research Funding; BMS: Speakers Bureau; MorphoSys, Bayer, Karyopharm, Kite, a Gilead Company, Novartis, Janssen, AbbVie, TeneoBio, and Pfizer: Consultancy; MorphoSys, AstraZeneca, BeiGene, Genentech, Kite, a Gilead Company, and Epizyme: Speakers Bureau. Shah: Pfizer: Consultancy, Other: Expenses; Incyte: Research Funding; Acrotech/Spectrum: Honoraria; BeiGene: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Precision Biosciences: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Other: Expenses; Servier Genetics: Other; Jazz Pharmaceuticals: Research Funding; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy. Nishihori: Karyopharm: Research Funding; Novartis: Research Funding. Lazaryan: Kadmon: Consultancy; Avrobio: Membership on an entity's Board of Directors or advisory committees; Humanigen: Membership on an entity's Board of Directors or advisory committees. Davila: Precigen: Research Funding. Locke: Wugen: Consultancy, Other; Umoja: Consultancy, Other; Cowen: Consultancy; EcoR1: Consultancy; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy. Gaballa: Adaptive Biotechnologies: Research Funding; Epizyme: Consultancy, Research Funding; TG therapeutics: Consultancy, Speakers Bureau; Beigene: Consultancy; ADC Therapeutics: Consultancy. Jain: Kite/Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.

Introduction: Prolonged cytopenias and infectious complications substantially contribute to the toxicity burden of CD19-directed CAR T-cell therapy (CAR-T). The latter represent the most common cause of non-relapse mortality after CAR-T. We have recently described the CAR-HEMATOTOX (HT) score, which integrates parameters associated with pre-CAR-T hematopoietic reserve (e.g. ANC, hemoglobin, platelet count) and inflammation (e.g. CRP, ferritin) to predict CAR-T-related hematotoxicity (Rejeski et al, Blood 2021). Here, we describe the utility of the HT score for identifying patients at risk for post-CAR-T infectious complications. Methods: In this multicenter retrospective analysis, we studied infection events occurring within the first 90 days after CAR-T in 248 patients receiving standard-of-care Axi-cel (n=138) or Tisa-cel (n=110) for relapsed/refractory LBCL. An episode of infection was defined as bacterial, viral or fungal based on microbiologic data or as a clinical syndrome of infection (e.g. pneumonia, cellulitis, cystitis) based on retrospective chart review. In the absence of clinicals signs or microbiologic data, fever was not counted as infection. Infection severity was classified on a 5-grade scale as mild, moderate, severe, life-threatening or fatal as previously established (Hill et al, Blood 2018). Severe (Grade ≥3) infections were defined as requiring i.v. anti-infective agents and/or hospitalization. Multivariate analysis was performed as binary logistic regression for the primary endpoint of grade ≥3 infection. Cumulative incidence curves were calculated as time-to-first-infection; hazard ratios were calculated by Cox proportional-hazards model. Results: In our cohort, the median duration of severe neutropenia (ANC85%) of infections occurred within the first 30 days with a median time to first infection of 7 days (95% CI: 5-8 days). Next, we performed multivariate analysis to study the influence of pre-CAR-T parameters on the binary outcome of grade ≥3 infection. When accounting for other host factors (e.g. sex, age, ASCT, LDH, disease entity), a high HT score was associated with an increased probability for grade ≥3 infection (Fig. 1A, OR = 7.6, 95% CI: 3.4 - 16.3). Overall, the rate of severe infections was significantly higher in HT High patients (38% vs. 8%, p < 0.001). When studying the distribution of infection grades, the majority of infections in HT Low patients were mild or moderate (83%). On the other hand, HT High patients predominantly developed grade ≥3 infections (58%) - including 17 life-threatening and 6 fatal infections in the first 90 days. The cumulative incidence of severe infections over time was significantly higher in HT High patients (Fig. 1B, HR = 6.4, 95% CI: 3.1 - 13.1). Of the infection subtypes, the negative impact of a high HT score was particularly evident for bacterial infections (HR = 2.2, 95% CI: 1.4 - 3.9). This translated into a longer median duration of hospitalization in HT High patients (20 vs. 16 days, p < 0.001, updated analysis), highlighting the clinical relevance and potential health economic impact of the score. Non-relapse mortality in our cohort was 6.0% (15/248) and was predominantly attributed to an infectious cause (10 infections, 3 CRS, 1 ICANS, 1 accident). Notably, a high HT score was associated with inferior overall survival (median: 8.6 months vs. not-reached, p < 0.001, updated analysis). Conclusions: These findings emphasize that early post-CAR-T infections are common in the real-world setting and are likely facilitated by prolonged neutropenia. The CAR-HEMATOTOX represents a useful and easy-to-apply clinical score to risk-stratify patients for these toxicities prior to lymphodepletion. The state of inflammation and hematologic reserve of the host thus predisposes for later infectious complications. In lieu of the high incidence of grade ≥3 infections in HT High patients, prospective evaluation of HT-adapted anti-infective prophylaxis and/or early G-CSF support appears warranted. Figure 1 Figure 1. Disclosures Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Penack: Novartis: Honoraria; Pfizer: Honoraria; Neovii: Honoraria; Astellas: Honoraria; Priothera: Consultancy; Shionogi: Consultancy; Omeros: Consultancy; Incyte: Research Funding; Gilead: Honoraria; Jazz: Honoraria; Therakos: Honoraria; MSD: Honoraria; Takeda: Research Funding. Buecklein: Novartis: Consultancy, Other: congress and travel support, Research Funding, Speakers Bureau; Miltenyi: Research Funding; BMS/Celgene: Consultancy, Research Funding; Kite/Gilead: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau. Blumenberg: Janssen: Research Funding; BMS/Celgene: Research Funding; Novartis: Consultancy, Research Funding; Kite/Gilead: Consultancy, Research Funding. Carpio: Regeneron, TAKEDA, Celgene, Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other. Bullinger: Bristol-Myers Squibb: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Gilead: Consultancy; Hexal: Consultancy; Janssen: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Menarini: Consultancy; Astellas: Honoraria; Sanofi: Honoraria; Seattle Genetics: Honoraria; Bayer: Research Funding. Locke: EcoR1: Consultancy; Gerson Lehrman Group: Consultancy; Emerging Therapy Solutions: Consultancy; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Amgen: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; Takeda: Consultancy, Other; Wugen: Consultancy, Other; Umoja: Consultancy, Other; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Novartis: Consultancy, Other, Research Funding; Janssen: Consultancy, Other: Scientific Advisory Role; Legend Biotech: Consultancy, Other; Cowen: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy. von Bergwelt: Astellas: Honoraria, Research Funding, Speakers Bureau; Miltenyi: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Mologen: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; MSD Sharpe & Dohme: Honoraria, Research Funding, Speakers Bureau. Bethge: Miltenyi Biotec: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite-Gilead: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Barba: Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, Jazz Phar,aceuticals: Honoraria; Cqrlos III heqlth Institute, aSOCIACION espanola contra el cancer, PERIS: Research Funding. Jain: Takeda: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria. Subklewe: Klinikum der Universität München: Current Employment; Janssen: Consultancy; Takeda: Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy, Speakers Bureau; Roche: Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; MorphoSys: Research Funding; Miltenyi: Research Funding; Gilead: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Research Funding, Speakers Bureau.

CD19-directed chimeric antigen receptor (CAR) T cell therapy with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) is approved for the standard of care treatment of relapsed or refractory large B cell lymphoma (LBCL). Patients with LBCL involving the gastrointestinal (GI) tract are at risk of perforation after lymphoma-directed therapy. The outcomes of CAR T cell therapy in patients with GI involvement have not been reported previously. This study aimed to determine the safety and efficacy of CD19 CAR T cell therapy in patients with LBCL involvement of the GI tract. This was a single-center retrospective study of 130 consecutive patients treated with standard of care or expanded-access axi-cel or tisa-cel for LBCL. Twenty-four of these patients had radiologic involvement of the GI tract before CAR T infusion. Incidence rates of severe immune effector cell-mediated toxicities and clinical outcomes were compared between the GI involvement and non-GI involvement groups. Three of the 24 patients with GI tract involvement experienced perforation. One patient had a contained gastric perforation after leukapheresis while receiving bridging radiation therapy to the stomach. This patient was eventually able to proceed with lymphodepletion and product infusion. In the other 2 patients, GI tract perforation occurred at day +13 and day +35 after CAR T infusion. All 3 patients subsequently died while experiencing lymphoma progression. Upper GI bleeding occurred in 1 other patient in the context of progressive disease at 6 months after product infusion. The incidence rates of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, length of hospital stay, and use of anti-IL-6 and steroids were similar in the 24 patients with GI tract involvement and the 106 patients without GI tract involvement. No significant between-group differences were seen in the best overall response rate, progression-free survival, or overall survival. Our data show that outcomes of patients with GI tract involvement before CAR T cell therapy are similar to those without GI involvement, and that durable remissions can be observed. However, patients with preexisting GI tract involvement are at risk of perforation from disease progression before and after CAR T cell infusion.

In this research a study of the adsorption of acetic, benzoic, butanoic, fumaric, maleic and succinic acids on sugarcane baggase ash is made. The adsorber material is characterized through physical criteria such as apparent and pictometric density, compressibility, porosity, superficial area and tortuosity. The sample has been examined by X-rays Diffraction, thermal analysis, IR-quality analysis. The isotherm for the sorption process is determined, where it is shown that the Freundlich model is adjusted to benzoic acid, the Langmuir and Toth model to acetic acid, Bunauer- Emmett- Teller (BET) model to succinic acid and the butiric, maleic and fumaric acids are adjusted to Langmoir model. It is established that the first-order model is adjusted to the adsorption kinetics of the acetic and benzoic acids; while the rest of the acids are adjusted to a second-order model, in the case of the butanoic, succinic and maleic acids it is possible the occurrence of chemisorption processes.

Introduction: Leukapheresis and adequate cell collection of patient derived T cells is critical in the successful manufacturing of chimeric antigen receptor T cell (CAR-T) therapy. There are limited published data on parameters that might affect quality of leukapheresis collection or collection efficiency (CE). The aim of this study is to identify patient characteristics or collection parameters that might affect leukapheresis CE and any potential impact on manufactured product characteristics. Methods: We retrospectively reviewed collection data from 23 consecutive patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) who underwent leukapheresis for Kymriah® (tisagenlecleucel) at our institution from May 1st, 2018 to July 1st, 2020. The study was approved by the Institutional Review Board. Non-stimulated mononuclear cell (MNC) collections were performed on the Spectra Optia, Terumo BCT, using the continuous MNC collection protocol. Acid citrate dextrose A (ACD-A) was used for anticoagulant. Inlet/AC ratio maintained at 15:1. Collection flow rates were targeted for 60-85 mL/min, with goal of processing 2-4 times the patient's total blood volume (TBV). Patients underwent peripheral collection if they had adequate venous access, otherwise central venous access was obtained. Peripheral blood (PB) flow cytometry was obtained prior to leukapheresis. Collection efficiency (CE) was calculated using the following formula: CE = Product CD3+ x106/ (PB CD3+ cells/μL x Total Volume Processed/ 1000). Descriptive summary statistics included median (range) for continuous variables and number (percentage) for categorical variables. Routine methods of continuous and categorical data analysis were performed using Statistica (version 7). Graph Pad Prism 8 was used to look for possible relations between variables. Results: Table 1 summarizes patient baseline characteristics (at time of leukapheresis) and pre-collection laboratory results. Table 2 summarizes the apheresis product. The median CE was 73% (with SD=13%). Baseline characteristics did not correlate significantly with collection efficiency. Collection by tunneled catheter or peripheral vein access did not significantly impact collection efficiency. PB absolute lymphocyte count (ALC) strongly correlated with PB CD3 cell and apheresis product CD3 counts (p Table 3 summarizes the tisagenlecleucel product information. Nine patients received out of specification (OOS) product due to low cell viability. All OOS products were due to cell viability below 80% threshold. When OOS products were compared to in specification products, OOS products were significantly associated with lower patient weight, less total volume processed, shorter collection run times, and smaller final collection product volumes. TBV processed was similar between groups. Conclusions: High CE is feasible in heavily pre-treated DLBCL patients, even with very low peripheral blood lymphocyte counts (ALC < 100). Our study confirms that pre-collection ALC and PB CD3 are strong indicators of CD3 yield in the leukapheresis collection product. OOS products were significantly associated with smaller volume processed, shorter run times, and smaller product volumes. This warrants further investigation. Disclosures Shah: NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive: Honoraria; Moffitt Cancer Center: Current Employment; Kite/Gilead, Jazz, Incyte: Research Funding. Nishihori:Karyopharm: Other: Research support to institution; Novartis: Other: Research support to institution. Locke:Calibr: Consultancy; Allogene: Consultancy; Cellular Biomedicine Group: Other: Consultancy with grant options; Celgene/Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Wugen: Consultancy; GammaDelta Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Jain:Kite/Gilead: Consultancy; Novartis: Consultancy.

In the present work we propose a fast and simple method, based on Laser Induced Breakdown Spectroscopy (LIBS), to evaluate Neutron Production Targets. Targets of interest consist of hydrogen (particularly deuterium or tritium) contained in a titanium matrix. The method aims to evaluate the relative content of hydrogen within the titanium matrix, in order to determine if the target is “accepted” or “rejected” according to this content. Several deuterium targets have been fabricated (TiD x ), with different deuterium concentrations, and different techniques have been used to characterize their surfaces. Optical Coherent Tomography has been used to characterize the size and shape of LIBS holes, in order to determine LIBS depth of analysis. Grazing Incidence X-ray Diffraction has been used to determine a range for deuterium relative content. Elastic Recoil Detection Analysis (ERDA) is proposed for future LIBS calibration, since it provides a single value for relative content, has a depth of analysis similar to LIBS and also allows to distinguish between different isotopes. ERDA first results are reported in comparison with LIBS results.

H bulk diffusion in Excel (Zr–3.5% Sn–0.8% Mo–0.8% Nb) was measured using the Laser Induce Breakdown Spectrometry (LIBS) technique in 469-660 K (196–387 oC) temperature range for the first time. D temperature dependence obeys the Arrhenius law with activation energy Q = (30 ± 3) kJ/mol and D0 = (3.0 ± 1.0)x10−8 m2/s. Those values are compatible with previous measurements of H diffusion in pure α-Zr and their alloys.

We explore the possible use of Laser Induced Breakdown Spectroscopy (LIBS) to analyze active materials in hot cells or even inside nuclear reactors where high radiation levels prevent the use of conventional techniques. LIBS measurements of the reaction-diffusion process in alloys used in the nuclear industry were compared with standard techniques such us micrography, scanning electron microscopy, and energy dispersive X-rays spectroscopy. The LIBS capability to qualitatively detect the above process was established. Also, the average speed of the reaction-diffusion process was measured through a temperature-dependent effective parameter K.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder defined as low platelet count with normal bone marrow in the absence of other causes of thrombocytopenia. It is caused by autoantibodies binding to several platelet surface antigens which lead to premature destruction of the platelet by the reticuloendothelial system. ITP can be primary or secondary, and it is known to be associated with various infections and drugs. K2/Spice, or synthetic marijuana, acts on cannabinoid receptors CB1 (cannabinoid type-1) and CB2 (cannabinoid type-2) with increased binding capacity compared to marijuana. A white male was brought to the emergency department with signs of acute drug toxicity. His urine drug test was negative but he admitted to a year long history of synthetic marijuana use. His platelet count was 12,000/mm and he was diagnosed with ITP. After receiving 2 doses of oral dexamethasone his platelets improved. Synthetic cannabinoids are widely available and used psychoactive drugs. Little is known about the complete chemical composition of the synthetic products thus there is relatively little information available on the pharmacodynamic and pharmacokinetic effects. A high index of suspicion is needed to diagnose toxicity to these drugs since there are no readily available on-site lab tests. Currently there exists 1 case report of ITP induced by K2/Spice. Here, we discuss another case of K2/Spice a as a potential cause of immune thrombocytopenia.

Type B lactic acidosis is a rare metabolic complication sometimes associated with hematologic malignancies. When present, this type of lactic acidosis is most commonly seen in patients with high-grade lymphomas or leukemias and is usually indicative of a dismal prognosis. We report a case of a 27-year man with acquired immunodeficiency syndrome (AIDS) that presented with bilateral lower extremity swelling, an abdominal mass, and weight loss. His lab values showed elevated anion gap with lactic acidosis and computed tomography (CT) of the abdomen showed a large soft-tissue mass arising from the left hepatic lobe. Biopsy of the abdominal mass demonstrated a high-grade diffuse large B-cell lymphoma. The patient’s lactic acidosis resolved after starting chemotherapy, and a complete response was evident on PET-CT after a third cycle of rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOC-RR). Care-givers should be aware of the implications of lactic acidosis associated with malignancy and the need for prompt diagnosis and treatment.

Background Among the subtypes of idiopathic inflammatory myopathy (IIM), it has been recognised that primary polymyositis (PM) and primary dermatomyositis (DM) have a worse prognosis than overlap syndrome (OM). However, the benign course of OM has not been confirmed in other studies. The identification of specific characteristics that could allow a correct classification may be important for its prognosis. Objectives To analyse clinical characteristics and survival of patients diagnosed with OM, and to compare if there are differences with other IIM subgroups in a multicentric cohort. Methods Retrospective, multicentric longitudinal observational study of a cohort of patients followed between January 1980 and December 2014, with a diagnosis of MII. The patients were divided into 2 groups: OM and primary idiopathic inflammatory myositis (PIIM), which included PM and DM. Patients classified as OM had to meet IIM criteria and criteria for rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) or primary Sjogren’s syndrome (SS). Results The present study included a total of 348 patients (98 OM, 250 PIIM). The connective tissue diseases associated with OM were: MCTD in 32 (32.7%), SSc in 29 (29.6%), SLE in 21 (21.4%), RA in 8 (8.2%) and SS in 8 (8.2%). Patients with OM showed remarkable differences compared to PIIM. In general, OM exhibited more extramuscular involvement and more complications, with more serious infections (41% vs. 24%, p Conclusions In the REMICAM registry of 348 inflammatory myopathies, 98 cases of myositis with overlap syndrome have been included, presenting with more extramuscular complications, more severe infections and higher mortality than other myopathies. It would be important to identify these patients at the onset of the disease, in order to closely monitor for development of possible complications. Disclosure of Interest None declared

Congenital deficiency of factor II is a very rare autosomal recessive disorder that can result in a bleeding diathesis. Genotypically, individuals are either homozygous for a defective prothrombin gene or a compound heterozygote with different mutated prothrombin genes inherited from each parent. Phenotypically, it is characterized by either a low production of normal prothrombin or a near-normal production of dysfunctional prothrombin. Treatment is aimed at restoring normally functioning factor II circulating levels to sufficient concentration for hemostasis. Paradoxical thrombosis in patients born from a nonconsanguineous marriage with factor II deficiency has not been reported. A woman with known congenital factor II deficiency confirmed by history and hemostatic laboratory analysis presented with an unprovoked spontaneous thrombosis of the common femoral vein detected on color Doppler. Venous thrombosis can occur in congenital deficiency of factor II and inferior vena cava filter can be life-saving.

RESUMEN Por medio de la espectrometría α se estudió la difusión de U en Zry-4 y se la comparó con la difusión en Zr-α puro en el rango de temperaturas que va de los 570 a los 820 ºC a fin de analizar el proceso difusivo en ambas matrices, sus similitudes y sus diferencias. Los valores del coeficiente de difusión D son sistemáticamente mayores en Zry-4, en tanto que su dependencia con la temperatura obedece a la ley de Arrhenius siendo D0 = (3,2 ± 1,1) m2/s y Q = (316 ± 9) kJ mol-1 en contraposición con el Zr-α que presenta un apartamiento a dicha ley consistente en una curvatura en el gráfico ln (D) vs 1/T. Por debajo de 600 ºC la solubilidad del U en Zry-4 es menor que en Zr puro. ABSTRACT Throughout the α-spectrometry U diffusion in pure Zry-4 was studied and compared with pure α-Zr in the temperature range 843-1093 K in order to analyze the diffusion process in both matrices. D values are systematically higher in Zry-4 and its temperature dependence obeys the Arrhenius law being: D0 = (3,2 ± 1,1) m2/s and Q = (316 ± 9) kJ mol-1, whereas in α-Zr U diffusion present an apart to this law, consistent in a downward curvature in the ln(D) vs 1/T plot. Below 873 K U solubility in Zry4 is lower than in pure Zr.

A comparative diffusion study of U in Ti and Zr in their hcp phase was performed by means of α-spectrometry in an extended temperature range, below half the melting point, which are the temperatures of technological interest (between 500 and 850 °C). The present diffusion coefficient (D) values for α-Ti differs from previous work in the literature, measured in samples with higher amount of impurities and less accurate techniques, in more than two orders of magnitude, whereas the present diffusion parameters Q = 297 kJ mol-1 and D0 = 5x10-3 m2 s-1, are close to the self-diffusion ones, which is compatible with a mechanism of diffusion assisted by vacancies. Diffusion data for U in α-Zr shows a curvature in the Arrhenius plot similar to the observed for α-Zr self-diffusion, with D values very close to the self-diffusion ones, which also indicates an assisted by vacancies diffusion mechanism, as expected.

The empirical literature on development has labelled as “middle-income trap” (MIT) the fact that many developing economies struggle to adjust to new sources of growth after reaching middle-income levels. For Latin America and the Caribbean, this is an especially challenging scenario, as only Chile, Trinidad and Tobago, and Uruguay have become high-income economies in the last six decades while several other LAC countries, already middle-income as early as 1950, stayed in that income range. This paper analyses empirically the main policy areas explaining the MIT, based on the experiences of 76 emerging economies and OECD countries, comparing those which evaded it and those which stayed there since the 1950s. Based on more than 200 000 estimations using a linear discriminant analysis, we identify institutional, social and economic features that help characterise policy priorities to overcome the middle-income trap. Furthermore, using the Synthetic Control Method, we present for selected Latin American countries their main policy gaps according to their unique characteristics.

Diffusion at infinite dilution of U in metals, with particular emphasis in those used in nuclear facilities, is revisited. Early works present some particularities such as activation enthalpies lower than the vacancy formation enthalpy in the matrix, large differences with self-diffusion in the base material, up to four orders of magnitude differences between measurements performed by different authors in similar temperature ranges, etc. In particular U self-diffusion was qualified as abnormal when compared with other metals. Recent studies by means of á-spectrometry reveal a normal behaviour: Activation enthalpies and pre-exponential factors similar to the self-diffusion one and diffusion coefficient values in the same order of magnitude than self-diffusion. The possible influence of short circuits, impurities and/or uncertainties in the techniques used in the early works is discussed in order to explain the differences obtained. Fil: Perez, Rodolfo Ariel. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

e18128 Background: The importance of population heterogeneity in clinical cancer research is universally recognized. This study aims to identify possible disparities in trial participation at UF Health Cancer Center at Orlando Health. Methods: Data on patients’ enrollment, during the period from 01/01/2016 to 12/31/2016, was obtained from our research C-base. We utilized descriptive statistics to characterize the main demographic variables. Pearson's Chi-squared and Z-tests were utilized to compare percentages of enrolled versus not enrolled patients by ethnicity, race and gender. Results: A total of 3704 cases were established as new patients during the study period, of which 369 (10%) were enrolled in cancer research studies (Table). Our analysis showed statistically significant differences in enrollment by racial category (χ2= 95.09, df = 3, p < 0.0000). American Indian (n = 6) and Native Hawaiian (n = 4), were excluded from the analysis due to small sample sizes and no enrollments. In addition we tested with the Z-stat whether the enrollment in each group was different from the population average (p = 0.10). The Caucasian group did not differ from the average (z = 0.3944; p < 0.6933), whereas both the African American (z = -4.2286; p < 0.0001) and the Asian group (z = -2.3102; p < 0.0209) were under enrolled. The Others group was above the average (z = 8.4632; p < 0.0001). There were also differences in enrollment by gender and ethnicity. Females were under enrolled as compared to Males (z = -7.0716; p < 0.0001). The Hispanic group enrollment was significantly below the population average (z = -4.17; p < 0.0001). Conclusions: We found significant differences in the enrollment of minorities in cancer trials in our institution. African Americans, Asians, Hispanics and Females were all under represented. The group labeled as Others requires further attention. [Table: see text]