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Simple Summary After the recent irruption of asciminib into the therapeutic arsenal for chronic myeloid leukemia, real-life data remain scarce to determine which patients may benefit most from this drug. Data on the efficacy of the drug in real-world setting have been reported, but a detailed analysis of the toxicity profile and the influence of prior intolerance to classical tyrosine kinase inhibitors (TKIs) has not been performed. The aim of the present analysis is to study in detail the toxicity profile of asciminib as well as to describe the risk of cross-toxicity with classical TKIs. These results may help to select the patient profile with the best chance of therapeutic success with asciminib monotherapy. (1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.

Multiple myeloma (MM) is a hematological neoplasm for which different chemotherapy treatments are used with several drugs in combination. One of the most frequently used drugs for the treatment of MM is the proteasome inhibitor bortezomib. Patients treated with bortezomib are at increased risk for thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, infection, and fatigue. This drug is almost entirely metabolized by cytochrome CYP450 isoenzymes and transported by the efflux pump P-glycoprotein. Genes encoding both enzymes and transporters involved in the bortezomib pharmacokinetic pathway are highly polymorphic. The response to bortezomib and the incidence of adverse drug reactions (ADRs) vary among patients, which could be due to interindividual variations in these possible pharmacogenetic biomarkers. In this review, we compiled all pharmacogenetic information relevant to the treatment of MM with bortezomib. In addition, we discuss possible future perspectives and the analysis of potential pharmacogenetic markers that could influence the incidence of ADR and the toxicity of bortezomib. It would be a milestone in the field of targeted therapy for MM to relate potential biomarkers to the various effects of bortezomib on patients.

We report the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020. After a median follow-up of 50 days, mortality was higher than in the general population and reached 48% in myelofibrosis (MF). Univariate analysis, showed a significant relationship between death and age, male gender, decreased lymphocyte counts, need for respiratory support, comorbidities and diagnosis of MF, while no association with essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic-PMF (pre-PMF) was found. Regarding MPN-directed therapy ongoing at the time of COVID-19 diagnosis, Ruxolitinib (Ruxo) was significantly more frequent in patients who died in comparison with survivors (p=0.006). Conversely, multivariable analysis found no effect of Ruxo alone on mortality, but highlighted an increased risk of death in the 11 out of 45 patients who discontinued treatment. These findings were also confirmed in a propensity score matching analysis. In conclusion, we found a high risk of mortality during COVID-19 infection among MPN patients, especially in MF patients and/or discontinuing Ruxo at COVID-19 diagnosis. These findings call for deeper investigation on the role of Ruxo treatment and its interruption, in affecting mortality in MPN patients with COVID-19.

Microglia, the innate immune cells of the brain, are exquisitely sensitive to dynamic changes in the neural environment. Using single cell RNA sequencing of the postnatal somatosensory cortex during topographic remapping, we identified a type I interferon (IFN-I) responsive microglia population that expanded with this developmental stressor. Using the marker gene IFITM3 we found that IFN-I responsive microglia were engulfing whole neurons. Loss of IFN-I signaling (

Resumen Antecedentes y objetivo La mielofibrosis es una neoplasia mieloproliferativa cronica infrecuente. Nuestro objetivo fue describir las caracteristicas clinico-biologicas, el tratamiento y el curso evolutivo de los pacientes con mielofibrosis en Espana. Material y metodos Se analizaron 1.000 pacientes del Registro Espanol de Mielofibrosis diagnosticados de mielofibrosis primaria (n = 641) o secundaria (n = 359). Resultados La mediana de edad era de 68 anos. La frecuencia de sintomatologia constitucional, anemia moderada o severa (Hb Conclusiones la mielofibrosis es una enfermedad invalidante que afecta sobre todo a personas de edad avanzada y cuyo tratamiento es fundamentalmente sintomatico. A pesar de su heterogeneidad clinica se dispone de modelos pronosticos utiles para la seleccion de candidatos a trasplante.

BACKGROUND AND OBJECTIVE MYELOFIBROSIS: is an infrequent chronic myeloproliferative neoplasm. We aimed to describe the clinico-biological characteristics, treatment, and evolutive course of myelofibrosis patients in Spain.; MATERIAL AND METHODS: A total of 1,000 patients from the Spanish Registry of Myelofibrosis diagnosed with primary (n=641) or secondary (n=359) myelofibrosis were analysed.; RESULTS: Median age was 68 years. The frequency of constitutional symptoms, moderate to severe anaemia (Hb

Landslides have become very frequent in Leyte which justifies the need for soil assessment and characterization of the landslide-prone areas in the province. This study assessed the physical characteristics of soils from the landslide areas in Cadac-an watershed in Leyte, Philippines. Landslide cuts located in the central highlands of Cadac-an watershed were used as representative profiles in this study. These were examined, characterized and sampled for the analyses of soil physical properties which include particle size distribution (Pipette method), bulk density (Paraffin-clod method), particle density (Pycnometer method), porosity, total soil wet density, water holding capacity and field capacity (Gravimetric method), saturated hydraulic conductivity (Constant head method), liquid limit and plastic index. Generally, soils from the landslide areas in Cadac-an watershed had a sandy loam to clay loam to clayey texture, low bulk density, low particle density, high porosity, moderate total soil wet density, moderate to high water holding capacity, low to moderate field capacity, moderately high to high saturated hydraulic conductivity, moderate liquid limit and low plastic index. Based on the above characteristics, the soils are susceptible to landslide occurrence thus it is highly recommended to conduct constant assessment and monitoring the area.

SummaryMicroglia are brain resident phagocytes that can engulf synaptic components and extracellular matrix as well as whole neurons. However, whether there are unique molecular mechanisms that regulate these distinct phagocytic states is unknown. Here we define a molecularly distinct microglial subset whose function is to engulf neurons in the developing brain. We transcriptomically identified a cluster of Type I interferon (IFN-I) responsive microglia that expanded 20-fold in the postnatal day 5 somatosensory cortex after partial whisker deprivation, a stressor that accelerates neural circuit remodeling.In situ, IFN-I responsive microglia were highly phagocytic and actively engulfed whole neurons. Conditional deletion of IFN-I signaling (Ifnar1fl/fl) in microglia but not neurons resulted in dysmorphic microglia with stalled phagocytosis and an accumulation of neurons with double strand DNA breaks, a marker of cell stress. Conversely, exogenous IFN-I was sufficient to drive neuronal engulfment by microglia and restrict the accumulation of damaged neurons. IFN-I deficient mice had excess excitatory neurons in the developing somatosensory cortex as well as tactile hypersensitivity to whisker stimulation. These data define a molecular mechanism through which microglia engulf neurons during a critical window of brain development. More broadly, they reveal key homeostatic roles of a canonical antiviral signaling pathway in brain development.

Simple Summary Azacitidine and decitabine have been increasingly used for the treatment of acute myeloid leukaemia in older patients. The choice between azacitidine and decitabine depends mostly on the experience and preference of the attending physician, since they have not been compared directly in a randomised clinical trial. In this study, we identified the best treatment regimen for each drug and compare the efficacy of decitabine and azacitidine monotherapy in newly diagnosed acute myeloid leukaemia. We found no significant differences regarding 1-year mortality and overall survival for azacitidine and decitabine (roughly 9 months). Moreover, there were no significant differences in the efficacy of 5-day versus 10-day schedules of decitabine. However, patients treated with the shortened 5-day azacitidine scheme showed worsened outcomes compared to the standard 7-day regimen. Hopefully, our results might be helpful for the design of azacitidine/decitabine-based combination schedules to be tested in future trials. Abstract Irruption of decitabine and azacitidine has led to profound changes in the upfront management of older acute myeloid leukaemia (AML). However, they have not been directly compared in a randomised clinical trial. In addition, there are no studies comparing the optimal treatment schedule of each drug in AML. A systematic review and meta-analysis on the efficacy of decitabine and azacitidine monotherapy in newly diagnosed AML was conducted. Randomised controlled trials and retrospective studies were included. A total of 2743 patients from 23 cohorts were analysed (10 cohorts of azacitidine and 13 of decitabine). Similar response rates were observed for azacitidine (38%, 95% CI: 30–47%) compared to decitabine (40%, 95% CI: 32–48%) (p = 0.825). Overall survival (OS) between azacitidine (10.04 months, 95% CI: 8.36–11.72) and decitabine (8.79 months, 95% CI: 7.62–9.96) was also similar (p = 0.386). Patients treated with azacitidine showed a lower median OS when azacitidine was administered for 5 days (6.28 months, 95% CI: 4.23–8.32) compared to the standard 7-day schedule (10.83 months, 95% CI: 9.07–12.59, p = 0.002). Among patients treated with decitabine, response rates and OS were not significantly different between 5-day and 10-day decitabine regimens. Despite heterogeneity between studies, we found no differences in response rates and OS in AML patients treated with azacitidine or decitabine.

As of April 23, 2020, the COVID-19 (SARS-CoV-2) pandemic has affected 2,544,792 people, causing 175,694 deaths worldwide. The global scientific community has turned its attention to the impact of the new virus, which has become a major challenge for healthcare systems in many countries. Oncology patients have been considered of high risk within the ongoing COVID-19 pandemic. Oncology patients are especially vulnerable to infection due to the underlying disease and the type of therapy received. In general, the epidemiologic behavior of community-acquired respiratory viruses among oncology patients resembles that of the general population. Although, at present, there is limited data regarding COVID-19 and solid tumors, oncology patients seem to carry a higher risk of developing severe events. Yet, among patients harboring hematological diseases we have not observed an increase in COVID 19 infections.

Patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting with splanchnic vein thrombosis (SVT) might have a specific clinico-biological profile. To investigate this hypothesis, 3705 PV/ET patients from three national registers, 118 of them presenting with SVT, were reviewed. After correction for age and sex, PV/ET patients with SVT showed an increased risk of death (HR 2.47, 95% CI 1.5–4.01, p

BACKGROUND AND OBJECTIVE MYELOFIBROSIS: is an infrequent chronic myeloproliferative neoplasm. We aimed to describe the clinico-biological characteristics, treatment, and evolutive course of myelofibrosis patients in Spain.A total of 1,000 patients from the Spanish Registry of Myelofibrosis diagnosed with primary (n=641) or secondary (n=359) myelofibrosis were analysed.Median age was 68 years. The frequency of constitutional symptoms, moderate to severe anaemia (Hb10g/dL), and symptomatic splenomegaly was 35%, 36%, and 17%, respectively. The rate of thrombosis and haemorrhage was 1.96 and 1.6 events per 100 patient-years, respectively. The cumulative incidence of leukaemia at 10 years was 15%. The most frequent therapies for the anaemia were the erythropoiesis stimulating agents and danazol. From 2010, a progressive increase in the use of ruxolitinib was noticed. A total of 7.5% of patients were transplanted. During the observation period, 42% of patients died mainly due to the clinical deterioration caused by myelofibrosis or leukaemic transformation. The median survival of the series was 5.7 years. Four different risk categories were identified by the IPSS: median survival was not reached in the low risk group and was 8.8 years, 5.3 years, and 2.8 years in the intermediate-1, intermediate-2, and high-risk groups, respectively.Myelofibrosis is a disabling condition mainly affecting elderly people. Its treatment is mostly driven by symptom control. Despite its clinical heterogeneity, several prognostic models are useful to select candidates for transplantation.

Introduction. MPN-COVID is a European LeukemiaNet cohort study, launched in March 2020 in patients with myeloproliferative neoplasms (MPN) with COVID-19. The first cohort of 175 cases was analyzed at the end of first wave (July 2020) and results provided estimates and risk factors of overall mortality (Barbui T. Leukemia, 2021), thrombosis incidence (Barbui T. Blood Cancer J, 2021), and post-COVID outcomes (Barbui T. Blood Cancer J, 2021). In the second wave of pandemic (June 2020 to June 2021), case-fatality risk in the general population has been found variable across different countries, and no information is available in MPN patients with COVID-19 diagnosed during the second wave in comparison with those of the first wave. Methods. In an electronic case report form, we registered a total of 479 cases of ET (n=161, 34%), PV (n=135, 28%), pre-PMF (n=49, 10%) and overt MF (n=134, 28%), from 39 European hematology units (Italy, Spain, Germany, France, UK, Poland, Croatia). Of these, 304 were diagnosed COVID-19 during the second wave. Results. Patients in the second wave were significantly different from those in the first wave, including parameters such as age (median: 63 vs. 71 years, p Conclusions. This is the largest series of MPN patients who incurred COVID-19 from June 2020 onward, namely during the "second COVID-19 wave". Compared to the first wave, the second one recorded a lower overall COVID-19 severity, but Ruxolitinib discontinuation still remained a risk factor for a dismal outcome. Greater vulnerability of ET than PV in developing venous thrombosis was confirmed also during the second wave. This finding suggests that ET warrants a specific antithrombotic prophylaxis in addition to heparin. Figure 1 Figure 1. Disclosures Barbui: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Iurlo: Novartis: Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Sobas: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Fox: Novartis: Honoraria; Sierra: Honoraria. Palandri: AOP: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Benevolo: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau. Harrison: Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sierra Oncology: Honoraria; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bonifacio: Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Kiladjian: Taiho Oncology, Inc.: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Other: Personal fees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Patriarca: Incyte: Honoraria; Takeda: Honoraria; Argenix: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria. Griesshammer: Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AOP Orphan: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Garcia Gutierrez: Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Osorio: Janssen, Abbvie, Roche: Consultancy. Koschmieder: CTI: Membership on an entity's Board of Directors or advisory committees, Other; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Other: Travel support; Alexion: Other: Travel support; Karthos: Other: Travel support; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Image Biosciences: Other: Travel support; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Shire: Honoraria, Other. Vannucchi: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees.

Introduction The occurrence of other neoplasms in patients diagnosed with chronic lymphocytic leukemia (CLL) is a known but insufficiently studied complication, highlighting the need for further research. Our study aims to analyze the incidence of other malignancies in CLL. Methods We performed a retrospective observational study of patients diagnosed with CLL between 2000-2016 at our center. Variables collected included: demographics, stage at diagnosis, treatment, response to treatment, death, other neoplasm (type, date of diagnosis, outcome), biomarker profiles studied by karyotyping, FISH, immunoglobulin heavy chain gene variable region mutational status, and TP53 mutational status. A descriptive study was performed. Quantitative variables are described as medians with their range, and qualitative variables as percentages. The relationship between qualitative variables and the development of second malignancies was performed using Chi-square and Fisher's exact test. Survival analyses were performed using the Kaplan-Meier method and the difference between groups was analyzed using the log-rank test. Results A total of 182 patients were evaluated, 104 men (57%) and 78 women (43%); median age: 74 years (39 - 97). Most patients were diagnosed at early stages (74% at Rai stage 0 and 84% at Binet stage A) and the median CIRS scale score at diagnosis was 4 (0 - 15). With a median follow-up of 76 months (20-212), 77/182 (42%) patients had received ≥1 line(s) of treatment: 1: 53%, 2: 26%, 3: 8%, ≥4: 13%. Forty-nine cases (27%) were reported with other malignancies in addition to CLL; cases with Richter transformation (n=5, 2.7%) were excluded. The diagnosis of CLL preceded the other neoplasm in 33/182 cases (18%): 8 hematologic and 27 non-hematologic neoplasms. Half of the hematologic malignancies involved MGUS (n=4), 1 mutated JAK2 (V617F) cMPN, 1 AML and 1 MALT lymphoma. As for non-hematologic tumors, non-melanoma skin cancer accounted for 30% of cases (n=8), followed by breast cancer (n=5, 18.5%). Neoplasms of the stomach, colon, liver, bladder and prostate together accounted for 37%, in the same proportion each (n=2, 7.4%). The remaining neoplasms corresponded to lung and bronchus, kidney, melanoma and pancreas. Five of the 27 patients had a third solid organ neoplasm, with non-melanoma skin cancer again being the most frequent (n=2). The other neoplasms were lung, small bowel and thyroid. The incidence of second neoplasms was higher in treated patients (26% vs. 12.4%, p=0.019). The incidence of a second hematologic malignancy was related to treatment administration (9%) compared to 1% in untreated patients (p=0.011), especially in those with ≥ 3 lines (37.5% vs. 3%), p=0.024. We could not find any association between the variables analyzed and the development of second non-hematologic malignancies. The development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. Conclusions The incidence of second malignancies is high in patients with CLL, being higher in those patients who have received treatment, and especially in those with a greater number of lines received. In contrast, the development of solid tumors did not seem to be affected by treatment administration, which should motivate further investigation in specific subgroups of patients. In our series, the development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. Disclosures Gonzalez-Lopez: Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Sobi: Other: Advisory board honoraria; Grifols: Other: Advisory board honoraria.

Background: Primary immune thrombocytopenia (ITP) is an immune-mediated acquired disorder characterized by impaired production and increased destruction of platelets with an elevated risk of bleeding. At present, diagnosis of primary ITP still remains one of exclusion with a need to discard other causes of isolated thrombocytopenia, in the absence of robust and accurate clinical and laboratory diagnostic criteria. For the diagnosis of ITP, a bone marrow (BM) study may be useful to differentiate between ITP and other diseases, such as myelodysplastic syndromes (MDS). Next generation flow (NGF) has emerged as a potential useful tool in these settings. Aim: In this study (FCR-PTI-2017-01) we prospectively evaluated the potential utility of NGF analysis of BM and peripheral blood (PB) for more accurate diagnosis of ITP vs MDS. Methods: 62 patients presenting with isolated thrombocytopenia and classified as ITP (n=20), MDS (n= 11) or inconclusive, i.e. unclassifiable, (n= 25) by BM cytomorphology, were studied. PB (n=47) and BM (n=62) analysis by NGF was blindly performed in parallel for the ITP, MDS and unclassifiable patient groups using the EuroFlow 8-colour AML/MDS classification antibody panel followed by automated analysis against pre-existing flow cytometry databases of normal healthy donor PB and BM immunophenotypic profiles. NGF BM and PB results were then compared with the BM cytomorphological diagnosis. In parallel, epidemiological data from patients were recorded in an electronic case report form (eCRF) and analyzed afterwards. Results: By cytomorphology, expert hematologists were able to conclude an ITP or MDS diagnosis in only 31 cases (55.3%). 62 BM and 48 PB samples with isolated thrombocytopenia were evaluated by NGF. Our 62 patients were allocated in 4 immunophenotypic groups attending to different BM variables observed: maturation blockades, abnormal antigen expression and cross lineage markers. Thus, we observed normal phenotype cases (n=10), isolated (unilineage) alterations (n=24), mild multilineage (>1) alterations (n=20) and severe multilineage (MDS-like) phenotypes (n=8). Cytomorphology diagnosed our cases as ITP, MDS or unclassifiable with a median number of alterations observed by BM NGF of 4 (IQR, 3-6), 2 (IQR, 1-6) and 4 (IQR, 3-5) respectively. For ITP cytomorphology group, NGF demonstrated numerous BM alterations being monocytic alterations (n=17, 94%) the most frequent finding observed. MDS presumed cases were also associated with monocytic alterations (50%) with a frequent decrease in neutrophil precursors (40%). On the contrary, when cytomorphology was not capable to establish a diagnosis, NGF showed a mixture of alterations with no clear predominance of none of them (table 1). Similarly to our work with BM NGF, we looked into a potential correlation of cytomorphology with PB NGF phenotypes. Thus, we observed a median number of alterations of 4 (IQR, 3-5), 4 (IQR, 2-4) and 4 (IQR, 3-5) in ITP, MDS and inconclusive cytomorphology groups. Increased platelet size and upregulated CD41, CD61 and CD63 glycoprotein (GP) expression were the most characteristic findings of ITP cohort. MDS subtype depicted an increased platelet size and overexpression of CD41. Downregulation of GP was restricted to patients with MDS-like phenotypes. (table 2). Nearly statistical significant differences at significance level of 90% were observed between cytomorphology and BM NGF results (p=0.179) (table 3), between platelet score and BM NGF findings (p=0.118) and also, among morphology, BM NGF and platelet score (p=0.179). Nevertheless, cytomorphology and PB NGF showed no statistical differences between them (p=0.206) (table 4). Conclusions: Limitations of BM cytomorphology when facing an isolated thrombocytopenia were demonstrated here. However, normal or unilineage BM NGF alterations may lead us to an ITP diagnosis while mild or severe multilineage BM phenotypes may correlate good with MDS. PB platelet GP expression allowed us to classify our patients in six groups (Gonzalez-Lopez/Matarraz platelet score) which may help ITP diagnosis when this score is low. Comparison of BM cytomorphology, BM NGF and PB NGF techniques at diagnosis showed statistically nearly comparable results (p=0.179), with a bigger amount of patients needed to confirm this trend. All these NGF findings may lead us to better address ITP at diagnosis. Figure 1 Figure 1. Disclosures Gonzalez-Lopez: Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Sobi: Other: Advisory board honoraria; Grifols: Other: Advisory board honoraria.

Introduction In the last decade, the incorporation of anti-CD20 monoclonal antibodies (MoAb) (rituximab, obinutuzumab), bendamustine, B-cell receptor inhibitors (ibrutinib) and Bcl-2 antagonists (venetoclax) have changed the paradigm of chronic lymphocytic leukemia (CLL) treatment, improving overall survival (OS). Methods We conducted a retrospective observational study of patients diagnosed with CLL between 2003 and 2016 at our center to evaluate: i) the influence of date of diagnosis, before or after 2010; ii) having received new drugs (MoAb or target therapies) in first line or not. Results A total of 182 patients were evaluated: 104 men (57%) and 78 women (43%); median age 74 years (39 - 97), 132 patients were >65 years (72.5%). At diagnosis, 135 (74%), 19 (10%), 15 (8%), 4 (2%) and 9 (5%) were diagnosed as stages 0, I, II, II, III and IV of the Rai classification. While 154 (84%) 15 (8%) and 14 (8%) were classified as Binet's stages A, B and C. Regarding the presence of comorbidities, the median CIRS scale score was 4 (0 - 15). 71 patients (39%) were diagnosed before 2010 and 111 (61%) from 2010 onwards. With a median follow-up of 76 months (range, 20-212), 77/182 (42%) patients had received ≥1 line(s) of treatment: 1: 53%, 2: 26%, 3: 8%, ≥4: 13%. 20 patients (26%) received the first line of treatment before 2010, and 56 (74%) from 2010 onwards. Half of the patients received new drugs in 1st line (n=39), 92% of them from 2010 onwards. 32 patients (41.5%) achieved complete response after 1st line, and 24 (31%) at least a partial response. The median OS of patients diagnosed before 2010 was 66 months (35.32 - 96.68) vs 143 months (95% CI 90.5 - 195.5) (p=0.032) as of 2010. In those ≤ 65 years median OS has not been reached, being 80.5% at 10 years: 65% for those diagnosed before 2010 and 97% after 2010, p=0.036. The median OS of patients > 65 years was 6 years (95% CI 4.17 - 7.83), and increased from 82 months for those diagnosed before 2010, to 110 months in those diagnosed after 2010, p=0.744. Patients treated with new drugs in 1st line increased the median OS from 76 months and 13% at 10 years to a median not reached and OS of 77% at 10 years, p=0.000. This difference was more evident in those ≤ 65 years: 20% vs 100% at 10 years (p=0.012), while it was not statistically significant for those > 65 years (11% vs 50% at 10 years, p=0.181) (Figure 1). However, in a multivariate model including age, sex, CIRS>6 and year of diagnosis (before or after 2010), treatment with new drugs retained statistical significance (HR 0.414; 95% CI 0.183 - 0.935) along with age ≤ 65 years (HR 0.256; 95% CI 0.085 - 0.771) and CIRS ≤ 6 (HR 0.247; 95% CI 0.111 - 0.551). Conclusions In our experience, the introduction of new drugs in the first line has led to an increase in OS, especially in young patients. Figure 1 Figure 1. Disclosures Gonzalez-Lopez: Grifols: Other: Advisory board honoraria; Sobi: Other: Advisory board honoraria; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Novartis: Other: Advisoryboard and speakers honoraria, Research Funding.

Introduction: asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor that potently inhibits aberrant kinase activity of the BCR-ABL1 oncoprotein via allosteric binding. asciminib has shown high efficacy profile in heavily pretreated Chronic Myeloid Leukemia (CML) patients with an adequate safety profile in phase I and III clinical trials. However, data from the use of asciminib in real life setting are still scarce. Methods: We gathered real-life retrospective data from 49 patients with BCR-ABL1 positive CML treated with asciminib (mean dose: 40 mg twice daily) between October 2018 and July 2021 at 33 institutions. The indication of asciminib was made according to the criterion of the attending physician and the drug was granted by Novartis under a controlled access program. Molecular biology tests were performed according to ELN guidelines and BCR-ABL/ABL ratios were expressed as % IS in all centers. Treatment responses were calculated with the patients at risk at each specific time points. For the event free survival (EFS), the events were treatment discontinuation due to any reason, progression or death. Data collection followed the local regulations for observational studies. Results: Median time on asciminib was 11,69 months for the entire cohort. Patients' characteristics are displayed on Table 1. Most patients were heavily pretreated with at least 3 prior TKI lines in 45 patients (91,83%), 18 of them receiving prior Ponatinib. Switch to asciminib occurred due to intolerance in 32 patients and due to resistance in the remaining 17. Fifteen patients (30,61%) harbored mutations in BCR-ABL1 (3 with a T315 mutation). Regarding efficacy (Table 2), probability of reaching or maintaining previous responses were 94%, 45% and 21% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Considering probabilities of improving previous response, rates were 40%, 42% and 33% for the same parameters. Probabilities to obtain CCyR and MMR in resistant and intolerant patients were 29% (4/14) vs 55% (6/11) and 27% (4/15) vs 52% (11/21), respectively. Amid the patients previously treated with Ponatinib, probabilities of reaching or maintaining previous response were 53% (9/17) and 35% (6/17) for CCyR and MMR respectively, and 30% (3/10), 23% (3/13) displayed improvement of response. Regarding responses in patients with mutations, 39% (5/13) achieved or maintained CCyR and 31% (4/13) MMR; whereas 20% (2/10) and 18% (2/11) improved such responses. Of the three patients with T315I mutation, one discontinued due to progression to advanced stages, and the rest maintained the previous response. With a median follow-up of 11,69 months, the estimated EFS was 80% (figure 1). In terms of safety (Table 3), the most frequent extra-hematological adverse events (AE) were: fatigue (16,2%), joint pain (13,5%) and nausea (8,1%), most of them grade 1-2. Grade 3-4 AE were observed in 10% of patient (fatigue (2), cholestasis enzyme elevation (1), hypertension (1), pancreatitis (1) and pericardial effusion (1)). Thrombocytopenia was shown as the most frequent AE (16,3%), with 6% of patients suffering from grade 3-4. Dose reduction was required in 15 patients (30,6%). After a median follow up of 51 weeks, 73,5% of the patients remained on treatment. Only fourteen patients discontinued treatment due to progression or loss of efficacy, whereas 6% of patients discontinuing treatment due to intolerance. Conclusions: The results presented are in line with the data obtained in clinical trials, positioning asciminib as a potential safe and efficacious treatment for CML patients with failure to several TKI lines. Figure 1 Figure 1. Disclosures Sanchez-Guijo: Novartis: Consultancy, Honoraria, Research Funding; Celgene/Bristol-Myers-Squibb,: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Introduction: Current recommendations for patients with low-risk polycythemia vera (PV) include hematocrit (Htc) control with phlebotomies and primary prophylaxis of thrombosis with low-dose aspirin. There is scarce information regarding the hematological control, the incidence of complications and the need for cytoreduction in PV patients treated with phlebotomies only. Methods: A total of 358 patients with low-risk PV ( Results: Baseline characteristics at the time of diagnosis are described in Table 1. Table 2 summarizes the main hematological and clinical characteristics under treatment with phlebotomies. Inadequate control of the Htc (> 45%) was reported in 61-70% of the patients, leukocytosis >15x10 9/l in 10% and thrombocytosis >1000x10 9/l in 5%. In addition, about 20% of the patients had pruritus and 10% had microvascular symptoms. Of the 358 patients included, 275 (77%) required cytoreduction, 261 (73%) with hydroxyurea and 14 (4%) with IFN. The main indication of cytoreduction was thrombocytosis (20%), followed by age >60 years old (15%) and microvascular symptoms (13%). Median duration of cytoreduction abstention was 4.7 (0.1-30.4) years being significantly longer in patients younger than 50 years (6 and 2 years for patients younger and older than 50 years, respectively, p With a follow-up of 1659 person-years under phlebotomy only treatment, 14 thrombosis were observed (arterial n=9, venous n= 5), 12 hemorrhages (major n=4, minor n=8) and 4 solid tumors (1 melanoma and 3 non-cutaneous carcinomas). The incidence of complications during the cytoreduction-free period by person-years was: 0.8% for thrombosis, 0.2% for major hemorrhage and 0.2% for second neoplasia. The median follow-up until last visit including the time after starting cytoreductive therapy was 8.4 (0.2-39) years. Of 14 deaths observed, none occurred during the phlebotomy period. Half of the patients died from PV related reasons but the other 50% were not related. The median survival estimation by K-M was 36.5 years. Disease progression was documented in 27 (7.5%) patients, 26 of them to myelofibrosis, 1 to myelodysplastic syndrome and none to acute leukemia. Progression to myelofibrosis occurred during the cytoreduction-free period in 5 patients (1.4%) after a median of 5.8 years (Range: 4.9-8.9). Conclusions The incidence of thrombotic and hemorrhagic complications was very low in this series of low-risk patients treated with phlebotomies, even though only 30-40% of patients maintained the Htc Representing the Spanish Group of Myeloproliferative Disorders. GEMFIN Figure 1 Figure 1. Disclosures Bellosillo: Qiagen: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding; Thermofisher Scientific: Consultancy, Speakers Bureau. Ferrer Marin: Cty: Research Funding; Incyte: Consultancy, Research Funding; Novartis: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Context: In the last decade, the incorporation of anti-CD20 monoclonal antibodies, bendamustine, B-cell receptor inhibitors, and Bcl-2 antagonists have changed the paradigm of chronic lymphocytic leukemia (CLL) treatment, improving overall survival (OS). Objective: To evaluate the influence of the date of diagnosis (before or after 2010) and whether new drugs were received as frontline therapy. Design: We conducted a retrospective observational study. Patients or Other Participants: Patients diagnosed with CLL between 2003 and 2016. Interventions: No intervention was performed. Main Outcomes Measures: OS. Results: One hundred eighty-two patients were evaluated: 104 men (57%) and 78 women (43%); median age 74 years (39–97). Seventy-one patients (39%) were diagnosed before 2010, and 111 (61%) from 2010 onward. With a median follow-up of 76 months (range, 20–212), 77/182 (42%) patients had received ≥1 line(s) of treatment. Twenty patients (26%) received the front-line treatment before 2010. Half of the patients received new drugs in first-line (n=39), 92% of them from 2010 onward. Median OS of patients diagnosed before 2010 was 66 months (35.32–96.68) vs 143 months (95% CI 90.5–195.5) (p=0.032) as of 2010. In patients ≤ 65 years, median OS has not been reached, being 80.5% at 10 years: 65% for those diagnosed before 2010 and 97% after 2010, p=0.036. Median OS of patients > 65 years was 6 years (95% CI 4.17–7.83) and increased from 82 months for those diagnosed before 2010, to 110 months in those diagnosed after 2010, p=0.744. Patients treated with new drugs in first-line had an increased median OS from 76 months and 13% at 10 years to a median not reached and OS of 77% at 10 years, p=0.000. This difference was more prominent in those ≤ 65 years: 20% vs 100% at 10 years (p=0.012), while it was not significant for those > 65 years (11% vs 50% at 10 years, p=0.181). However, in a multivariate model, treatment with new drugs retained statistical significance (HR 0.414; 95% CI 0.183–0.935). Conclusions: The implementation of new drugs in the front line has led to an increase in OS, especially in young patients.

Context: Decitabine and azacitidine have been increasingly used to treat patients with acute myeloid leukemia (AML) who are elderly or not suitable for intensive chemotherapy. Despite their widespread use, there is no consensus on their efficacy, with considerable variability between studies. Objective: Our aim was to analyze and compare the efficacy of azacitidine and decitabine for the treatment of AML in elderly patients and/or patients not suitable for intensive chemotherapy. Design: A systematic review and meta-analysis was conducted. Patients or Other Participants: Trials were selected if performed on patients not eligible for intensive chemotherapy. The meta-analysis only includes data from the azacitidine or decitabine monotherapy arms; data from experimental arms were excluded from the analysis. Interventions: The results were summarized using a point estimate and 95% confidence interval (CI) for the means of the different outcomes between studies. Main Outcome Measures: Studies had to report at least one of the following outcomes: mortality, overall survival (OS), complete remission, complete remission with incomplete hematological recovery, or partial response. Results: The search strategy revealed 681 citations before duplicates were removed. Finally, 20 articles were included after analysis of abstracts and full text. A total of 3,000 patients from 23 cohorts were analyzed (12 cohorts of azacitidine and 11 of decitabine). A trend toward lower response rates was observed for azacitidine (31%, 95%CI: 24%–37%) compared to decitabine (40%, 95%CI: 31%–49%o, p=0.081). However, there was no significant difference in OS between azacitidine (9.99 months, 95%CI: 8.17–11.82) and decitabine (8.88 months, 95%CI: 7.67–10.08, p=0.550). Lower 1-year mortality with standard 7-day 75 mg/m2 azacytidine treatment was observed compared to other azacitidine schedules (51%, 95%CI: 46%-57% vs 72%, 95%CI: 61%-82%, p=0.001). Moreover, OS was lower when administered for 5 days (6.28 months, 95%CI: 4.23-8.32) versus 7 days (10.90 months, 95%CI: 8.92–12.89, p=0.002). However, there was no significant difference in response rates, mortality, and OS when comparing the 5-day vs 10-day decitabine regimens. Conclusions: There were no significant differences in 1-year mortality or OS for azacitidine and decitabine (roughly 9 months). These results exploring single-HMA regimens could be useful for the design and use of new HMA-based combination schedules.

Introduction: Decitabine and azacitidine have been increasingly used to treat patients with acute myeloid leukemia (AML) who are elderly or not suitable for intensive chemotherapy. Despite their widespread use, there is no consensus on their efficacy, with considerable variability between studies. Furthermore, they have not been directly compared in a randomized clinical trial. Our aim was to analyze and compare the efficacy of azacitidine and decitabine for the treatment of AML in elderly patients and/or patients not suitable for intensive chemotherapy. Methods: We included randomized controlled trials and retrospective studies enrolling adults diagnosed with newly diagnosed AML and treated with azacitidine or decitabine, not eligible for intensive chemotherapy. Only data from azacitidine or decitabine monotherapy arms were included. We included studies that reported at least one of the following outcomes: mortality, overall survival (OS), complete remission (CR), complete remission with incomplete hematologic recovery (CRi), partial response (PR). Results: The search strategy revealed 681 citations, before the duplicates were removed. Finally, 20 articles were included after analysis of abstracts and full text. In total, 23 patient cohorts were analysed (12 for azacitidine and 11 for decitabine). Table 1 shows the results of response, OS and 1-year mortality during azacitidine (75mg/m2 for 7d and 5d) and decitabine (20 mg/m2 for 5d and 10d) treatment. Comparing only the standard regimens, the overall response rate (ORR=CR+RCi+RP) for azacitidine (75 mg/m2, 7d) was 30% (95% CI 23%-37%) and for decitabine (20mg/m2, 5d) was 46% (95% CI 42%-50%), p75%), and the result was significantly different between azacitidine (51% mortality, 95%CI: 46% -57%) and decitabine (72% mortality, 95%CI: 67% -76%), p Comparing the 5-day versus 10-day decitabine regimen, an ORR of 46% (95% CI 42-50) and 40% (95% CI 25-56), respectively, was observed (p=0.420). There was no significant difference in response rates, mortality and OS. For treatment with azacitidine for 5 days vs 7 days, an ORR of 36% (95% CI 13-60) and 30% (95% CI 23-37), respectively, was observed (p=0.613). Mortality was higher when administered for 5 days (72%, 95% CI: 61-82%) versus 7 days (51%, 95% CI: 46-57%), p=0.001. OS was lower when given for 5 days (6.28 months, 95% CI: 4.23-8.32 months) versus 7 days (10.9 months, 95% CI 8.92 -12.89 months), p=0.002. Conclusions: There is a lot of heterogeneity between the different studies. Despite this, it is observed that, although the ORR rate is higher in the case of decitabine than azacitidine, there are no significant differences in mortality at 1 year and in OS, which for both azacitidine and decitabine is close to 9 months. Furthermore, this study shows that there are no significant differences in the administration of decitabine for 5 or 10 days, but there are differences in the administration of azacitidine, with the recommended regime being 7 days. Disclosures No relevant conflicts of interest to declare.

Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience. The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program. Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0). Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects. Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs. Disclosures Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.

Background We analyze the cost of an incorrect application, by the haematologist, of bridging anticoagulation in patients with low-risk atrial fibrillation (AF) needing interruption of treatment prior to a scheduled invasive procedure. Although not recommended, bridging therapy is widely used, resulting in avoidable costs and increased workload. Methods Observational retrospective study. We recorded demographic and clinical data including age, sex, type of procedure, use of bridging therapy with low molecular weight heparin (LMWH), and haemorrhagic complications within 30 days of acenocoumarol withdrawal. Results Acenocoumarol was stopped in 161 patients, 97 (60%) were male and 64 (40%) female. Average age was 76,11 ± 8,45 years. Procedures included: minor surgical intervention 58 (36%), colonoscopy 61 (38%), gastroscopy 11 (7%), breast biopsy 4 (2.5%), prostate biopsy 4 (2.5%), infiltration 5 (3%), and other 18 (11%). All patients received bridging anticoagulation with LMWH (40 mg enoxaparin per day) 3 days before and 3 days after the procedure (6 doses). We used a total of 966 doses, at €4.5 per unit, resulted in €4347 of total cost. No complications occurred in 156 patients (97%). Haemorrhage was observed in 5 cases: 1 major haemorrhage needing 6 days of hospital stay and transfusion, and 4 minor haemorrhages (2 patients needed emergency attendance and 2 required hospital admission for 3 and 2 days, respectively). The cost of emergency care was €237.36, and the cost of hospital stay was €6860.81 (€623.71 per day, for 11 days). The total cost of the incorrect application of the protocol was €11,445.17. Conclusion Guidelines about bridging anticoagulation in low risk AF patients undergoing scheduled invasive procedures were not followed. This practice increments the complications and supposes an increase in costs besides to an inadequate use of the human resources.

Creative thinking is necessary to generate novel ideas and solve problems. "EstuPlan" is a methodology in which knowledge and creativity converge for the resolution of scientific problems with social projection. It is a training programme that integrates teachers, laboratory technicians and PhD students, master and undergraduate students which form working groups for the development of projects. Projects have a broad and essential scope and projection in terms of environmental problems, sustainable use of natural resources, food, health, biotechnology or biomedicine. The results show the success of this significant learning methodology using tools to develop creativity in responding to scientific and social demand for problem-solving to transfer academic knowledge to different professional environments. Bioplastics, Second Life of Coffee, LimBio, Algae oils, Ecomers, Caring for the life of your crop and Hate to Deforestate are currently being developed.

Background and objective. Idelalisib is an oral inhibitor of the p110δ isoform of PI3K (phosphoinositide 3-kinase) approved in Europe and USA as monotherapy in relapsed/refractory follicular lymphoma (FL) after 2 previous lines of therapy based on a phase 2 study (Gopal et al, N Eng J Med 2014). However, there are scarce data on the use of idelalisib in clinical practice (Eyre et al, Br J Haematol 2017). The objective of this study was to analyze the efficacy and toxicity of idelalisib in relapsed/refractory FL patients in clinical practice in Spanish hospitals of GELTAMO group (GELT-IDE-2018-02 Study). Patients and Methods. Retrospective study of relapsed/refractory FL patients treated with idelalisib as salvage therapy in clinical practice. Demographic and clinical and biological variables were analyzed at FL diagnosis and at the time of idelalisib therapy, as well as its efficacy and toxicity. Results. A total of 43 patients from 20 hospitals were included. At time of idelalisib therapy, median age was 63 years (range 44-83), number of previous lines of therapy was 3 (2-7), 42% (n=18) were refractory to last previous treatment and 42% (n=18) had received an autologous stem cell transplantation (SCT); 56% (n=24) had progressed in the first 24 months after FL diagnosis (POD24). Median duration of treatment with idelalisib at time of analysis was 8.1 months (1.1-37.4) and 28/43 patients (65%) discontinued therapy, 13 due to progression, 12 due to adverse events (AE) and 3 due to physician's decision. Overall response rate (ORR) was 73% (32% CR) and median PFS 14.6 months (95% CI 0-32.2), with a trend to be higher in non-POD24 group (median PFS of 9.4 months [95% CI 1.7-16.9] in POD24 vs. 27 months [95% CI NA] in non-PO24 patients, p=0.082); median duration of response to idelalisib was 25.1 months (95% CI 13.1-37.6). Median overall survival (OS) was not reached at the time of analysis, with a 2-year OS of 74% (95% CI 58%-90%) (Figure). In 4 patients, an allogeneic SCT was performed after idelalisib. A total of 86% (n=37) of patients showed any AE, being in 56% (n=24) of grade ≥3 AE. Toxicities of grade ≥3 more frequent were: neutropenia (23% of patients), diarrhea (23%), infections (23%: pneumonia in 4 patients, CMV infection in 2, febrile neutropenia in 1 and other infections in 3 [1 of them died due to Aspergillus infection]), and increased transaminases (9%). Conclusions. In this series of patients with relapsed/refractory FL, several previous lines of therapies and factors associated with poor prognosis, the treatment with idelalisib was associated with efficacy and toxicity similar to published studies. These results support the use of idelalisib as an option for FL patients with multiple or poor risk relapses. Financial support: Gilead Figure. Progression-free survival (PFS) and overall survival (OS) for patients with follicular lymphoma treated with idelalisib. Figure Disclosures Sancho: SERVIER: Honoraria; SANOFI: Honoraria; Novartis: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; JANSSEN: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ROCHE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GILEAD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CELLTRION: Consultancy; Kern-Pharma: Honoraria; Sandoz: Consultancy. Lopez Jimenez:GILEAD SCIENCES: Honoraria, Other: Education funding. Ramirez Payer:GILEAD SCIENCES: Research Funding. Cordoba:Janssen: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Kyowa-Kirin: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Roche: Honoraria, Speakers Bureau; FUNDACION JIMENEZ DIAZ UNIVERSITY HOSPITAL: Employment; Celgene: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy. Martín:Kiowa Kirin: Consultancy; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; iQone: Consultancy; Teva: Research Funding; Janssen: Honoraria, Other: Travel Expenses, Research Funding; Roche: Consultancy, Honoraria, Other: Travel Expenses; Servier: Honoraria, Other: Travel Expenses. Armando:Roche: Consultancy, Research Funding; Janssen: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Long-term starvation provokes a metabolic response in the brain to adapt to the lack of nutrient intake and to maintain the physiology of this organ. Here, we study the changes in the global proteomic profile of the rat brain after a seven-day period of food deprivation, to further our understanding of the biochemical and cellular mechanisms underlying the situations without food. We have used two-dimensional electrophoresis followed by mass spectrometry (2D-MS) in order to identify proteins differentially expressed during prolonged food deprivation. After the comparison of the protein profiles, 22 brain proteins were found with altered expression. Analysis by peptide mass fingerprinting and MS/MS (matrix-assisted laser desorption-ionization-time of flight mass spectrometer, MALDI-TOF/TOF) enabled the identification of 14 proteins differentially expressed that were divided into 3 categories: (1) energy catabolism and mitochondrial proteins, (2) chaperone proteins, and (3) cytoskeleton, exocytosis, and calcium. Changes in the expression of six proteins, identified by the 2D-MS proteomics procedure, were corroborated by a nanoliquid chromatography-mass spectrometry proteomics procedure (nLC-MS). Our results show that long-term starvation compromises essential functions of the brain related with energetic metabolism, synapsis, and the transmission of nervous impulse.

Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9–163) months, and median duration on bosutinib was 9 months (1–30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients’ cohort. Pleural effusions and diarrhea were the most frequent grade II–IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.