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In myelodysplastic syndromes (MDS), the 20q deletion [del(20q)] may cause deletion of the ASXL1 gene. We studied 153 patients with MDS and del(20q) to assess the incidence, prognostic value and impact on response to azacitidine (AZA) of ASXL1 chromosomal alterations and genetic mutations. Additionally, in vitro assay of the response to AZA in HAP1 (HAP1(WT)) and HAP1 ASXL1 knockout (HAP1(KN)) cells was performed. ASXL1 chromosomal alterations were detected in 44 patients (28 center dot 5%): 34 patients (22%) with a gene deletion (ASXL1(DEL)) and 10 patients (6 center dot 5%) with additional gene copies. ASXL1(DEL) was associated with a lower platelet count. The most frequently mutated genes were U2AF1 (16%), ASXL1 (14%), SF3B1 (11%), TP53 (7%) and SRSF2 (6%). ASXL1 alteration due to chromosomal deletion or genetic mutation (ASXL1(DEL)/ASXL1(MUT)) was linked by multivariable analysis with shorter overall survival [hazard ratio, (HR) 1 center dot 84; 95% confidence interval, (CI): 1 center dot 11-3 center dot 04; P = 0 center dot 018] and a higher rate for acute myeloid leukaemia progression (HR 2 center dot 47; 95% CI: 1 center dot 07-5 center dot 70, P = 0 center dot 034). ASXL1(DEL)/ASXL1(MUT) patients were correlated by univariable analysis with a worse response to AZA. HAP1(KN) cells showed more resistance to AZA compared to HAP1(WT) cells. In conclusion, ASXL1 alteration exerts a negative impact on MDS with del(20q) and could become useful for prognostic risk stratification and treatment decisions.

Introduction : The 20q deletion [del(20q)] is a recurrent chromosomal aberration in myelodysplastic syndromes (MDS) and, as a single abnormality, is associated according to the Revised International Prognostic Scoring System (IPSS-R) with a favorable outcome. However, the breakpoint of del(20q) is very heterogeneous and may cause deletion of the ASXL1 gene (20q11.21). This gene is an important epigenetic regulator of hematopoiesis and its mutations have been associated in MDS with a shorter overall survival (OS) and a lower response to azacitidine (AZA). Aim: To assess the incidence, prognostic value and impact on response to AZA of ASXL1 chromosomal alterations and genetic mutations in MDS patients with del(20q). Methods: We studied 153 patients diagnosed with MDS and del(20q) as a sole abnormality (n=93), with an additional chromosomal abnormality (n=27) or in a complex karyotype (n=33). Response to AZA therapy was assessed using the 2006 International Working Group (IWG) criteria. Analysis of ASXL1 chromosome alterations was performed by FISH (Empire Genomics probe). Samples with ASXL1 alterations by FISH were analyzed using the Agilent SurePrint G3 Human CGH 8x60K Microarray. Mutations of ASXL1 were detected by Sanger sequencing. SF3B1, SRSF2, U2AF1, DNMT3A, IDH1, IDH2, TP53, RUNX1, and SETBP1 mutations were screened by high-resolution melting and positives were confirmed by Sanger sequencing. An in vitro assay of the response to AZA in HAP1 and HAP1 ASXL1 knockout cell lines (Horizon) was also performed. The association of the clinical characteristics with the molecular findings was analyzed with the SPSS statistical program (v.20.0) and P values Results: Main patient characteristics are shown in Table 1.ASXL1 chromosomal alterations were detected by FISH in 44 patients (29%; Fig. 1): 34 patients (22%) with gene deletion (ASXL1DEL) and 10 cases (6.5%) with additional gene copies (ASXL1GAIN). All 44 cases were analyzed by microarray, and alterations in centromeric KIF3B gene (20q11.21) were also identified in 24 patients (16%). Patients with ASXL1DEL showed a lower platelet count (median, 68x109/L vs. 103x109/L, P=0.046), a poorer response to AZA (response, 9% vs. 43%, P= 0.040) and a trend towards a lower OS (34 vs. 65 months, P=0.057). ASXL1 and KIF3B chromosomal gains were associated with complex karyotypes (ASXL1GAIN, 80% vs. 23%, P Conclusion: In MDS patients with del(20q), the alteration of ASXL1 by chromosome deletion or somatic mutation was associated with adverse clinical features and a poorer response to AZA. Its detection at diagnosis would allow the rapid identification of a subgroup of MDS patients with a poor prognosis that could benefit of earlier and more effective therapies. Disclosures Sanz: Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; LaHoffman Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Ltd.: Membership on an entity's Board of Directors or advisory committees. Tormo:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees.

This work analyzes the efficiency of the ground penetrating radar (GPR) technique for the evaluation of strength grading of structural sawn timber. For this end, tests were performed on pinus radiata timber samples using GPR and other common evaluation techniques: visual grading and ultrasound-based evaluation. In order to determine the level of reliability of the different grading methods for timber structures, the results obtained with each method are compared to the results obtained from experimental bending-strength tests undertaken in accordance with standard EN408. Finally, the level of reliability of the GPR technique is compared to that of the other methods analyzed in this paper. The results obtained in this work show that GPR can be a valuable tool for the evaluation of structural timber, since it is a non-destructive technique, fast and easy to use, and what is more important, more reliable than other current evaluation methods used for timber grading.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is one of the most common malignant neoplasms in elderly patients, potentially curable when optimum treatment is administered. The combination of rituximab with CHOP chemotherapy (R-CHOP) is considered standard for these patients, but randomized studies published to date are limited to the range of age from 60 to 80 years, so that in patients over this age treatment election is not so clear, usually opting for palliative treatment or a "full" treatment at a reduced dose. This retrospective study is primarily aimed to analyze the influence of the type of treatment and comorbidity scales in overall survival (OS) of a large series of patients >80 years with aggressive B-cell lymphoma. Methods: Eligible patients were aged ≥ 80 years, diagnosed of DLBCL, follicular lymphoma grade 3B or transformed lymphoma. The main patient characteristics were obtained retrospectively from the medical records, including a complete geriatric assessment (CGA, "comprehensive geriatric assessment") and the Charlson comorbidity index. The Ethics Committee of the University Hospital of Salamanca approved the study. Results: 288 patients from 19 GELTAMO hospitals were registered in the study, of which 234 (60% women) were evaluable and have been included in this preliminary analysis. The median age was 84 years (80-94) and the vast majority (94%) were DLBCL. According to the Charlson index, 65% of patients were low-intermediate risk, and according to CGA, 63% of patients were considered "fit". A higher proportion (60% v 44%, p = 0.03) of patients with low or intermediate comorbidity index were treated with a curative intent (CHOP +/- rituximab), as compared with patients with high or very high index. With a median follow up of 41 (range 9-142) months, the median OS was 11.5 months (33% estimated at 3 years). The median OS for patients treated with R-CHOP-like (N=96) was 35.3 months, significantly better (p Conclusions: In patients over 80 years with DLBCL, treatment with R-CHOP-like was associated with the best results in terms of OS. Therefore, its administration must be considered whenever possible. Disclosures Sancho: CELLTRION, Inc.: Research Funding.