INTERREGIONAL R&D SPILLOVERS IN EUROPE

Our paper identifies and estimates the effects of R&D spillovers on total factor productivity with consideration of spatial effects. We first run our estimations on the Coe and Helpman (1995) model introducing spatial correlation. The results show positive R&D spillover effects on TFP and high spatial dependency among countries. We then run the same estimations on regional data. Due to a lack of information about trade between regions, we construct our trade matrix using regional transport information. We obtain a trade matrix for 57 European regions. Estimation results confirm spatial dependency and positive spillovers effects.PRODUCTIVITY, PANEL, COINTEGRATION, SPATIAL MODEL, EUROPEAN REGIONS

Gemtuzumab Ozogamicin and Stem Cell Mobilization for Autologous Stem Cell Transplantation in Favorable Risk Acute Myeloid Leukemia.

Gemtuzumab ozogamicin (GO), a CD33-targeting antibody drug conjugate, previously showed longer relapse-free survival when combined with induction chemotherapy in patients with favorable-risk acute myeloid leukemia (AML). In this patient population, characterized by lower relapse risk as compared to other ELN risk groups, autologous stem cell transplantation (ASCT) can be used as consolidation strategy. However, there are limited data on the impact of GO on the peripheral blood stem cell (PBSC) mobilization potential. We therefore retrospectively analyzed data from 54 AML patients with favorable-risk AML treated with (n = 17) or without (n = 37) GO during induction treatment. We observed no significant differences in the PBSC mobilization rate between patients treated with vs. without GO. The mobilization success in a first attempt directly following cycle 2 was 65% vs. 70% (p = 0.92); and the mobilization success in a subsequent second attempt after hematologic recovery and repeated stimulation procedure was 24% vs. 19% (p = 0.56). No significant impact on treatment outcome in terms of EFS (p = 0.31) or OS (p = 0.99) was observed. Thus, our results suggest that the addition of GO to induction regimens does not negatively impact PBSC mobilization in favorable-risk AML patients. To our best knowledge, this is the first study comparing the stem cell mobilization potential in favorable-risk AML patients treated with vs. without GO

Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a rare type of B-cell Non-Hodgkin lymphoma (NHL) affecting predominantly male patients. While complete remissions following first-line treatment are frequent, most patients ultimately relapse, with a usually aggressive further disease course. The use of cytarabine-comprising induction chemotherapy and autologous stem cell transplantation, Rituximab maintenance, Bruton's tyrosine kinase (BTK) inhibitors and CAR T therapy has substantially improved survival. Still, options for patients relapsing after CAR T therapy are limited and recommendations for the treatment of these patients are lacking. We report two cases of patients with mantle cell lymphoma who relapsed after CAR T therapy and were treated with the bispecific CD20/CD3 T cell engaging antibody glofitamab. Both patients showed marked increases of circulating CAR T cells and objective responses after glofitamab administration. Therapy was tolerated without relevant side effects in both patients. One patient completed all 12 planned cycles of glofitamab therapy and was alive and without clinical progression at the last follow-up. The second patient declined further treatment after the first cycle and succumbed to disease progression. We review the literature and investigate possible mechanisms involved in the observed responses after administration of glofitamab, such as proliferation of CAR T cells, anti-tumor effects of the bispecific antibody and the role of other possibly contributing factors. Therapy with bispecific antibodies might offer an effective and well-tolerated option for patients with mantle cell lymphoma relapsing after CAR T therapy

Correlation of plasma cell assessment by phenotypic methods and molecular profiles by NGS in patients with plasma cell dyscrasias.

BACKGROUND Next-generation sequencing (NGS) detects somatic mutations in a high proportion of plasma cell dyscrasias (PCD), but is currently not integrated into diagnostic routine. We correlated NGS data with degree of bone marrow (BM) involvement by cytomorphology (BMC), histopathology (BMH), and multiparameter flow cytometry (MFC) in 90 PCD patients. METHODS Of the 90 patients the diagnoses comprised multiple myeloma (n = 77), MGUS (n = 7), AL-amyloidosis (n = 4) or solitary plasmocytoma (n = 2). The NGS panel included eight genes CCND1, DIS3, EGR1, FAM46C (TENT5C), FGFR3, PRDM1, TP53, TRAF3, and seven hotspots in BRAF, IDH1, IDH2, IRF4, KRAS, NRAS. RESULTS Mutations were detected in 64/90 (71%) of cases. KRAS (29%), NRAS (16%) and DIS3 (16%) were most frequently mutated. At least one mutation/sample corresponded to a higher degree of BM involvement with a mean of 11% pathologic PC by MFC (range, 0.002-62%), and ~ 50% (3-100%) as defined by both BMC and BMH. CONCLUSIONS The probability of detecting a mutation by NGS in the BM was highest in samples with > 10% clonal PC by MFC, or > 20% PC by BMC/ BMH. We propose further evaluation of these thresholds as a practical cut-off for processing of samples by NGS at initial PCD diagnosis

Correlation of cytomorphology and histopathology in the diagnostic process of myeloid malignancies

Bone marrow cytomorphology and histopathology are the cornerstones for the initial diagnosis of myelodysplastic syndromes (MDS) and other related myeloid disorders. They provide a rapid first insight into diagnostic categories and thus help in clinical decision making. However, difficulties in the morphologic assessment of MDS exist due to inter- and intra-observer variability. In this study, we directly compared the results of cytomorphology and histopathology obtained in a real-world diagnostic scenario in 90 patients with myeloid malignancies aiming to evaluate their validity for diagnosing and classifying various myeloid malignancies. While both techniques placed 80% of our bone marrow samples into the same diagnostic category and thus showed a good correlation, our study also demonstrates the limitations in correlating marrow cytomorphology and histopathology, even following stringent and repetitive diagnostic assessments. This was particularly true for CMML, where not only additional diagnostic tools such as molecular genetics or clinical evaluation but also the analysis of the peripheral blood smears aided in finding the correct diagnosis. Overall, our data emphasize the need for a comprehensive diagnostic review in a patient-for-patient setting when a myeloid malignancy is suspected or confirmed. We propose that the combination of cytomorphologic and histopathologic assessment with clinical, laboratory, and genetic parameters is essential in achieving high diagnostic accuracy in an interdisciplinary setting

Adding bendamustine to melphalan before ASCT improves CR rate in myeloma vs. melphalan alone: A randomized phase-2 trial.

Definite cure remains exceptional in myeloma patients even after high-dose chemotherapy (HDCT) with melphalan (Mel) and autologous stem cell transplantation (ASCT). Thus, improving efficacy of HDCT in MM remains an unresolved issue. This randomized phase II trial compared standard 200 mg/m2 Mel HDCT to experimental HDCT with 200 mg/m2 bendamustine, given both at days -4 and -3, combined with 100 mg/m2 melphalan at days -2 and -1 (BenMel) before ASCT as first-line consolidation in myeloma patients. The primary endpoint aimed to identify at least a 15% improvement in the complete remission rate (stringent CR + CR) after HDCT with BenMel compared with Mel alone. A total of 120 MM patients were 1:1 randomized. The rate of sCR/CR after ASCT was higher in BenMel than in Mel treated patients (70.0% vs. 51.7%; p = 0.039). Three patients in the BenMel group (5.0%) had reversible acute renal insufficiency compared with none in Mel patients. Minimal residual disease negativity (<10-5) by flow cytometry was observed in 26 (45.6%) BenMel patients and 22 (37.9%) in the Mel group (p = 0.375). Our data suggest that BenMel HDCT is safe and improves the sCR/CR rate compared with standard Mel alone

Comprehensive Laboratory Diagnostic Workup for Patients with Suspected Intraocular Lymphoma including Flow Cytometry, Molecular Genetics and Cytopathology.

BACKGROUND Intraocular lymphoma (IOL) presents a real challenge in daily diagnostics. Cyto- and/or histopathology of vitreous body represent the diagnostic cornerstones. Yet, false negative results remain common. Therefore, we analyzed the diagnostic significance of flow cytometry (FC) within the workup algorithm of IOL and compared its sensitivity with the results obtained from routine cytopathology and molecular genetics; Methods: Seven patients undergoing vitrectomy due to suspected IOL were investigated by FC and parallel cytopathology and, if available, digital droplet PCR (ddPCR) for MYD88 L265P; Results: Four out of seven patients were finally diagnosed with IOL. Among the IOL patients, cytopathology confirmed the presence of lymphoma cells in only two cases. In contrast, FC was positive for IOL in all four cases, and FC additionally confirmed the lack of IOL in the remaining patients. In IOL patients diagnosed by FC and with available ddPCR, the diagnosis of IOL was confirmed by the presence of the MYD88 L265P mutation in all three patients; Conclusions: The combination with FC was superior to cytopathology alone in the diagnostic work-up of IOL, and it showed an excellent correlation with ddPCR results. A comprehensive diagnostic panel consisting of cytopathology, FC and molecular genetics should be considered for the work-up of suspected IOL

Maîtriser le français écrit à l'université : un simple problème de langue ?

Le défaut de maîtrise de l'écrit chez de nouveaux étudiants n'est pas seulement affaire de compétence linguistique. Les carences sont plus largement partagées dans la structuration logique des textes, dans leur adéquation rhétorique ou pragmatique aux consignes. Il faut donc vérifier certaines représentations, héritées du programme scolaire, qui perturbent l'accès à une verbalisation efficace des savoirs: celles du langage scientifique, des rapports entre formes et contenus, des tâches et de la communication scolaires. C'est ce qu'on illustre ici par les exemples de la définition, du résumé et de l'analyse de questions ou de plans de réponses.Difficulties which new students have in mastering written language are not solely linked with linguistic competence. Difficulties have been observed in text structure and in rhetorical or pragmatic response to directions. The author proposes to examine students' representations of school programmes as these representations appear to interfere with the following knowledge: scientific language, relation between form and content, school tasks and communication. This article offers examples including the production of a definition, a résumé, and an analysis of questions and response outlines.La falta de maestria del idioma escrito en estudiantes de primer afio no es solamente un problema de aptitud linguistica. Las carencias se observan mâs frecuentemente en la estructuraciôn logica de textos y en la adecuacion teôrica o pragmatica a las consignas. Por ende, hay que verificar ciertas representaciones heredadas del programa escolar, que perturban el acceso a una verbalizacion eficaz del saber. Dichas representaciones comprenden las del lenguaje cientiflco, las de las relaciones entre formas y contenidos, y las de las tareas y la comunicaciôn escolares. Todo ésto es ilustrado en el présente texto a través de ejemplos de definicion, resumen y anâlisis de preguntas o de planes de respuesta.Die mangelnde Beherrschung des Schriftlichen unter den neuen Studenten ist nicht nur Sache sprachwissenschaftlicher Fâhigkeiten. Die Mangel lassen sich aufierdem im logischen Aufbau der Texte, in der rhetorischen oder tatsachlichen Befolgung von Vorschriften beobachten. Man mutë also gewisse auf schulische Curricula zuruckgehende Vorstellungen uberprûfen, welche den Zugang zu wirksamem Ausdruck der Kenntnisse stôren: die wissenschaftliche Sprache, das Verhâltnis zwischen Form und Inhalt, schulische Aufgaben und Kommunikation. Dies wird hier and den Beispielen der Definition, der Zusammenfassung und der Analyse von Fragen oder Entwurfen von Antworten illustriert