TY - THES A1 - Gründahl, Marie T1 - Inzidenz und assoziierte Letalität invasiver Mykosen bei Patienten mit akuter lymphatischer Leukämie T1 - Incidence and mortality of invasive fungal diseases in patients with new diagnosed acute lymphoblastic leukemia N2 - Invasive Mykosen stellen bei Patienten mit hämatologischer Grunderkrankung eine lebensbedrohliche Komplikation dar. Im Rahmen dieser retrospektiven monozentrischen Studie wurde die Inzidenz und Letalität invasiver Mykosen bei erwachsenen Patienten mit einer neu diagnostizierten akuten lymphatischen Leukämie erfasst, sowie die Krankheitsverläufe und der Einfluss einer antimykotischen Prophylaxe analysiert. In der untersuchten Kohorte war eine erhöhte Inzidenz invasiver Mykosen feststellbar, ebenso wie eine negative Beeinflussung des Krankheitsverlaufs durch invasive Mykosen. Es konnte kein signifikanter Nutzen einer antimykotischen Prophylaxe verzeichnet werden. Eine diagnostisch gesteuerte Therapie der invasiven Mykosen ist anzustreben. Die Frage nach dem Nutzen einer antimykotischen Prophylaxe bleibt auch in dieser Arbeit nicht abschließend geklärt. Eine großangelegte prospektive Studie hierzu wäre wünschenswert. Durch Risiken insbesondere hinsichtlich schwerwiegender Medikamenteninteraktionen scheinen aktuell jedoch retrospektive Daten mit individuell angesetzter Prophylaxe die einzige mögliche Näherung an diese Fragestellung zu sein. N2 - Invasive mycoses are a life-threatening complication for patients with underlying hematological diseases. In this retrospective monocentric study, incidence and lethality of invasive mycoses in adult patients with newly diagnosed acute lymphoblastic leukemia were recorded. Furthermore, the courses of disease and the effect of antifungal prophylaxis were analyzed. An increased incidence of invasive mycoses was observed, as well as a negative influence of invasive mycoses on the course of disease. No significant benefit of antimycotic prophylaxis was evident. To improve the patients’ outcomes, a diagnostic-driven therapy should be pursued. The benefit of antimycotic prophylaxis is not conclusively clarified in this study. A large-scale prospective study on this matter would be advisable. However, especially regarding severe drug interactions, retrospective data with individually applied prophylaxis seems to be the only reasonable approach at this time. KW - Mykose KW - Lymphatische Leukämie KW - Akute Leukämie KW - Antimykotikum KW - acute lymphoblastic leukemia KW - mycosis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206434 ER - TY - JOUR A1 - Deak, Dalma A1 - Pop, Cristina A1 - Zimta, Alina-Andreea A1 - Jurj, Ancuta A1 - Ghiaur, Alexandra A1 - Pasca, Sergiu A1 - Teodorescu, Patric A1 - Dascalescu, Angela A1 - Antohe, Ion A1 - Ionescu, Bogdan A1 - Constantinescu, Catalin A1 - Onaciu, Anca A1 - Munteanu, Raluca A1 - Berindan-Neagoe, Ioana A1 - Petrushev, Bobe A1 - Turcas, Cristina A1 - Iluta, Sabina A1 - Selicean, Cristina A1 - Zdrenghea, Mihnea A1 - Tanase, Alina A1 - Danaila, Catalin A1 - Colita, Anca A1 - Colita, Andrei A1 - Dima, Delia A1 - Coriu, Daniel A1 - Einsele, Hermann A1 - Tomuleasa, Ciprian T1 - Let’s Talk About BiTEs and Other Drugs in the Real-Life Setting for B-Cell Acute Lymphoblastic Leukemia JF - Frontiers in Immunology N2 - Background: Therapy for acute lymphoblastic leukemia (ALL) are currently initially efficient, but even if a high percentage of patients have an initial complete remission (CR), most of them relapse. Recent data shows that immunotherapy with either bispecific T-cell engagers (BiTEs) of chimeric antigen receptor (CAR) T cells can eliminate residual chemotherapy-resistant B-ALL cells. Objective: The objective of the manuscript is to present improvements in the clinical outcome for chemotherapy-resistant ALL in the real-life setting, by describing Romania's experience with bispecific antibodies for B-cell ALL. Methods: We present the role of novel therapies for relapsed B-cell ALL, including the drugs under investigation in phase I-III clinical trials, as a potential bridge to transplant. Blinatumomab is presented in a critical review, presenting both the advantages of this drug, as well as its limitations. Results: Bispecific antibodies are discussed, describing the clinical trials that resulted in its approval by the FDA and EMA. The real-life setting for relapsed B-cell ALL is described and we present the patients treated with blinatumomab in Romania. Conclusion: In the current manuscript, we present blinatumomab as a therapeutic alternative in the bridge-to-transplant setting for refractory or relapsed ALL, to gain a better understanding of the available therapies and evidence-based data for these patients in 2019. KW - blinatumoman KW - acute lymphoblastic leukemia KW - bridge-to-transplant KW - real life setting KW - bispecific antobodies Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193921 SN - 1664-3224 VL - 10 IS - 2856 ER - TY - JOUR A1 - Rouhigharabaei, Leila A1 - Ferreiro, Julio Finalet A1 - Tousseyn, Thomas A1 - van der Krogt, Jo-Anne A1 - Put, Natalie A1 - Haralambieva, Eugenia A1 - Graux, Carlos A1 - Maes, Brigitte A1 - Vicente, Carmen A1 - Vandenberghe, Peter A1 - Cools, Jan A1 - Wlodarska, Iwona T1 - Non-IG Aberrations of FOXP1 in B-Cell Malignancies Lead to an Aberrant Expression of N-Truncated Isoforms of FOXP1 JF - PLOS ONE N2 - The transcription factor FOXP1 is implicated in the pathogenesis of B-cell lymphomas through chromosomal translocations involving either immunoglobulin heavy chain (IGH) locus or non-IG sequences. The former translocation, t(3; 14)(p13; q32), results in dysregulated expression of FOXP1 juxtaposed with strong regulatory elements of IGH. Thus far, molecular consequences of rare non-IG aberrations of FOXP1 remain undetermined. Here, using molecular cytogenetics and molecular biology studies, we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3; 14)(p13; q32)/IGH-FOXP1 and FOXP1-expressing lymphomas with no apparent structural aberrations of the gene. Our study revealed that non-IG rearrangements of FOXP1 are usually acquired during clinical course of various lymphoma subtypes, including diffuse large B cell lymphoma, marginal zone lymphoma and chronic lymphocytic leukemia, and correlate with a poor prognosis. Importantly, these aberrations constantly target the coding region of FOXP1, promiscuously fusing with coding and non-coding gene sequences at various reciprocal breakpoints (2q36, 10q24 and 3q11). The non-IG rearrangements of FOXP1, however, do not generate functional chimeric genes but commonly disrupt the full-length FOXP1 transcript leading to an aberrant expression of N-truncated FOXP1 isoforms (FOXP1NT), as shown by QRT-PCR and Western blot analysis. In contrast, t(3; 14)(p13; q32)/IGH-FOXP1 affects the 59 untranslated region of FOXP1 and results in overexpress the full-length FOXP1 protein (FOXP1FL). RNA-sequencing of a few lymphoma cases expressing FOXP1NT and FOXP1FL detected neither FOXP1-related fusions nor FOXP1 mutations. Further bioinformatic analysis of RNA-sequencing data retrieved a set of genes, which may comprise direct or non-direct targets of FOXP1NT, potentially implicated in disease progression. In summary, our findings point to a dual mechanism through which FOXP1 is implicated in B-cell lymphomagenesis. We hypothesize that the primary t(3; 14)(p13; q32)/IGH-FOXP1 activates expression of the FOXP1FL protein with potent oncogenic activity, whereas the secondary non-IG rearrangements of FOXP1 promote expression of the FOXP1NT proteins, likely driving progression of disease. KW - lymphoid-tissue lymphomas KW - acute lymphoblastic leukemia KW - transcription factor FOXP1 KW - cardiomyocyte proliferation KW - chromosomal aberration KW - prostate cancer KW - down regulation KW - poor prognosis KW - malt lymphoma KW - gene Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117679 SN - 1932-6203 VL - 9 IS - 1 ER -