Background: We examined whether or not extended prophylaxis with low molecular weight heparin (LMWH) would significantly reduce thromboembolic event (TEE) rates in germ cell cancer patients undergoing cisplatin-based chemotherapy. Patients and Methods: LMWH prophylaxis was given from the first day of chemotherapy until 21 days after completing the last chemotherapy cycle to 45 out of 93 (48.4%) patients (extended), and to 48 out of 93 (51.6%) patients during their hospitalization only (limited) between January 2008 and December 2013. Patients were analyzed retrospectively for TEEs such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) or peripheral arterial thrombosis. Results: A total of 22/93 (23.7%) patients experienced 30 TEE during chemotherapy: 12 out of 30 (40%) deep vein thrombosis, 4 out of 30 (13.3%) MI, 10 out of 30 (33.3%) PE and 4 out of 30 peripheral arterial thrombosis (13.3%). TEE rates in both groups did not differ significantly (extended: 26.7 vs. limited: 20.8%). Conclusions: The introduction of extended LMWH prophylaxis did not significantly reduce TEE rates in our patient cohort.

Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al. Eur J Haematol 73:62-66, 2004), including ex vivo antileukemic immune responses which may contribute to the long-lasting spontaneous CR (tantamount to cure). We could demonstrate strong in vitro cytotoxic activity mediated by the patient's serum (cryopreserved at diagnosis 2001) against myeloid cell lines. We also addressed cellular cytotoxic activity against myeloid leukemia cells. When the patient's natural killer (NK) cells (obtained in 2007) were tested against the K562 cell line, upregulation of CD107 occurred, implying that long-term CR in this patient could be due to NK cell-mediated disease control.

Purpose To promote nationwide dissemination and implementation of COVID-19 Risk Assessment and Safety Management Operational Guidelines, drawn up by SAMeR Task Force in ART centers in Argentina. Our objective is to prevent and mitigate the transmission of SARS-CoV-2 at an institutional level, while reducing the risk of infection among both physicians and patients in the context of a critical scenario in the local and Latin American healthcare system. Methods SAMeR Executive Committee set up a crisis committee which was made up of specialists in reproductive medicine, embryology, and healthcare management. A critical and updated review of the advances in science, documents, and recommendations released by other societies (ASRM, ESHRE, IFFS, Red LARA, societies of anesthesiologists, infectious diseases, and Occupational Safety and Health Administration-OSHA) was carried out. Likewise, there were joint meetings with the Ministry of Health of Argentina in order to draw up the guidelines. Simultaneously, ongoing medical training was carried out, thus providing added value to them, including two status surveys of the activities of the monovalent and polyvalent centers according to the country's epidemiological mapping. Four additional recommendations were made, and online training was given to healthcare workers. The aforementioned regulations were first analyzed by the healthcare providers and their practical suggestions were then added to the guidelines. Results The one-off collaborative work and the actions coordinated with the National ART Program of the Ministry of Health of Argentina resulted in the development and implementation of the present COVID-19 Risk Assessment and Safety Management Operational Guidelines at a national level. SAMeR gave recommendations for the implementation of the Management Guidelines for the center reopening, providing new safety criteria against the threat of viral contagion. A new organizational culture was promoted through the awareness of all the healthcare workers and teaching responsibility. We continue working on the compliance with a new "Code of Conduct and Commitment in Healthcare" and with workplace safety measures. We helped with transforming the theoretical knowledge into practical measures for the healthcare workers in different services, with the aim to prevent, mitigate, and/or handle contingencies at the centers/services and gamete banks, in line with the actions agreed upon with the Ministry of Health. Conclusions As an extraordinary and uncertain event, the SARS-CoV-2 pandemic helped consolidate a volunteer-based and collaborative panel of SAMeR experts who developed the COVID-19 Risk Assessment and Safety Management Operational Guidelines as a new and readily available tool for physicians, patients, and gamete banks care. Their implementation has provided specific guidelines to minimize risk for professionals in ART clinics, as well as guaranteeing patient safety.

Summary The leukaemia‐specific fusion oncoprotein RUNX1/RUNX1T1 (AML1/ETO), resulting from the chromosomal translocation (8;21) in acute myeloid leukaemia (AML), imposes a striking genotype–phenotype relationship upon this distinct subtype of AML, which is mediated by multiple, co‐ordinate downstream effects induced by this chimeric transcription factor. We previously identified the LAT2 gene, encoding the adaptor molecule LAT2 (NTAL, LAB), which is phosphorylated by KIT and has a role in mast cell and B‐cell activation, as a target of the repressor activity of RUNX1/RUNX1T1. These results were confirmed and extended by demonstrating downregulation of the LAT2 protein in response to conditional RUNX1/RUNX1T1 expression, and its absence in primary AML with the t(8;21). In contrast, in a cohort of 43 AML patients, higher levels of LAT2 were associated with myelomonocytic features. Differentiation of HL‐60 and NB4 cells towards granulocytes by all trans‐retinoic acid (ATRA) resulted in downregulation of LAT2; conversely, it was upregulated during phorbol ester‐induced monocytic differentiation of HL‐60 cells. Forced expression of LAT2 in Kasumi‐1 cells resulted in a striking block of ATRA‐ and phorbol ester‐induced differentiation, implicating disturbances of the graded expression of this adaptor molecule in the maturation block of myeloid leukaemia cells.

Prognostic factors and clinical outcomes of high-dose chemotherapy followed by autologous stem cell transplantation in patients with peripheral T cell lymphoma, unspecified: complete remission at transplantation and the prognostic index of peripheral T cell lymphoma are the major factors predictive of outcome.

5119 Introduction: It has been previously reported that both short and long term vascular and thromboembolic events (TEE) occur following cisplatin containing chemotherapy for germ-cell cancer (GCC) (Bokemeyer et al. 1998, Weijl et al. 2000, Diekmann et al. 2010). It has also been shown that patients with GCC are at higher risk of TEE than patients with non-GCC, while on cisplatin-based chemotherapy (Piketty et al. 2005). Method: We reviewed all GCC patients treated in our department from 2008 until 2010 with cisplatin-based chemotherapy and assessed the incidence of TEE. Cases were analyzed with respect to risk factors for vascular events (obesity, diabetes, nicotine abuse, prior cardiovascular disease, prior TEE), tumor characteristics (low- vs. intermediate/high-risk GCC) and age. In addition, further analysis of hemostasis laboratory tests of these patients is being performed. Result: Eight patients (8/50=16%) treated with cisplatin-containing chemotherapy developed TEE. Of these TEE, two were myocardial infarctions, four pulmonary embolisms, one patient showed thrombosis of the jugular vein and one a peripheral (femoral) arterial thrombosis. TE-risk factors included: nicotine abuse in two patients, obesity and nicotine abuse in one patient and no identifiable factors in the others (hemostasis laboratory tests are currently being performed). The median age of these 8 patients was 42 years (range 16–61). Patients were treated with PEB (cisplatin, etoposide, bleomycin) or PIV (cisplatin, ifosfamide, etoposide) initially applying continuous heparin prophylaxis with 15000IE/day (d), d1-5 only during PEB or PIV, but no low-molecular weight heparin (LMWH-) and/or aspirin (ASS-) medication for venous and arterial TEE prophylaxis thereafter. With these clinically very relevant and severe TEEs, we have adapted our PEB- and PIV protocols, adding a LMWH prophylaxis (enoxaparin 40mg d6-21 after chemotherapy). Conclusion: We observed an increased risk of major thromboembolic and vascular events with an incidence rate of 16% in GCC patients after cisplatin-containing chemotherapy. Prior studies have identified TEE-risks in GCC and with cisplatin-chemotherapy, albeit LMWH- and/or ASS-prophylaxis - without clinical trials - has not been recommended as yet. Prospective studies investigating thrombosis prophylaxis measures are currently performed in order to achieve the best standard of care for these patients. Currently an extensive hemostasis diagnostic testing from all patients with TEE is being performed. Disclosures: No relevant conflicts of interest to declare.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

2474 Background: The leukemia-specific oncofusion protein AML1/ETO regulates different target genes, including the LAT2 gene (encoding the adaptor molecule LAT2/NTAL/LAB), which is epigenetically repressed by AML1/ETO as we have previously described. LAT2 is phosphorylated by c-kit and has a role in mast cell and B cell activation. To address the functional role of LAT2 during myeloid differentiation, expression studies were performed in myeloid cell lines, and LAT2 was overexpressed by retroviral gene transfer in AML1/ETO-positive Kasumi-1 cells and AML1/ETO-negative U-937 cells. Methods: To induce monocytic and granulocytic differentiation, the myeloid cell lines U-937, HL-60 and NB4 were treated with PMA and ATRA, respectively, and LAT2 expression measured by both Northern and Western blot. LAT2 was overexpressed in Kasumi-1 and U-937 cells by use of the retroviral vector pMYSiG-IRES-GFP. Virus was produced in 293T cells and titrated in TE671 cells. Following transduction, GFP-positive cells were sorted by fluorescence-activated cell sorting (FACS). Transduced cells were treated with PMA (2 and 10 nM for 24 and 48 hours) and ATRA (0.1 μM and 0.5 μM for 48 and 96 hours), respectively. Results: The AML1/ETO-negative myeloid cell lines HL-60, NB4 and U-937 readily expressed LAT2, which was further upregulated by PMA, and transiently downregulated with ATRA. In the AML1/ETO-positive Kasumi-1 and SKNO-1 cells, LAT2 expression was absent. To address the functional role of this repression, forced expression of LAT2 was achieved in Kasumi-1 and U-937 cells and resulted in effective processing of LAT2 protein (confirmed by Western blot), and a decrease in the expression of the differentiation markers CD11b and CD11c (FACS analysis) in Kasumi-1 but not U-937, with only minor effects of LAT2 overexpression upon apoptosis and cell growth arrest. Notably, during both PMA- and ATRA-induced differentiation, a striking maturation block occurred in Kasumi-1 (measured by CD11b/CD11c expression, observed at different doses and time points of these treatments), while differentiation of U-937 cells was unimpaired by overexpression of LAT2. Conclusions: In AML1/ETO-negative leukemia cells, LAT2 expression is differentially regulated during monocytic and granulocytic differentiation. In AML1/ETO-positive leukemia cells, in which LAT2 is repressed, LAT2 re-expression imposes a striking maturation block. Graded expression of this novel AML1/ETO target gene may therefore play an important role in maintaining the phenotypic characteristics of this leukemia subtype. Disclosures: No relevant conflicts of interest to declare.