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The importance of assessing the financial distress risk of a company is a topic that has been of central value in many different economic fields and since a long time. Until the twenty-first century, most of the studies were concentrated primarily on using mathematical and statistical methods to assess the health of businesses. Many of these studies employed either accounting-based ratios or cash flow-based ratios; even if there is not a unique conclusion, the use of cash flows seems to improve the predictive capacity of the models significantly. Especially in the last twenty-five years, methods derived from different fields started to be applied in forecasting corporate failures, such as artificial neural networks, genetic algorithms, and fuzzy logic.The objective of this study was to test the goodness of the discriminatory power of ratios based only on cash flows using a model that employs genetic algorithms and fuzzy logic. Five countries (Germany, Spain, France, Great Britain, Italy) and five Nace macro sectors (Agriculture, Industry, Services, Construction, Commerce and Food) have been considered in the analysis for a total of around 719-thousand companies. The model has proven to be well-performing on most of the countries and sectors that have been tested. The results obtained are almost all adequate; in particular, in Germany and Spain, results have been particularly good.The main weaknesses of this work are the limited availability of financial data in some countries and the time delay from the reporting of financial statement to the availability of the data through web services. It means that a large-scale risk assessment requires – being useful for the public and the private sectors – greater and faster disclosure of information at European level, and standardization of financial information transparency among countries.

The knowledge of Langerhans Cell Histiocytosis (LCH) is based on pediatric studies. Adults with LCH are usually treated with pediatric protocols. In 2001, guidelines for adults with LCH (GIMEMA LCH 2001) were proposed, in order to standardize the diagnostic and therapeutic approaches for this category of patients. The aims of this retrospective study are: a) to evaluate the role of a multidisciplinary assessment in adults with LCH, according to the GIMEMA LCH 2001 guidelines, and b) to analyze the results obtained with the GIMEMA LCH 2001 guidelines and those obtained with pediatric protocols. Pts aged >18 years with a diagnosis of LCH (S-100+, CD1a+, CD207+) managed at our Institution since 1985 to 2018 were considered. As diagnostic and treatment approaches, two different strategies were used over time: the GIMEMA LCH 2001 guidelines and the pediatric protocols. The GIMEMA LCH 2001 guidelines included a multidisciplinary diagnostic work-up with complete odontostomatologic, pulmonary and endocrinologic assessments; treatment strategy consisted of: wait and see or local therapy in unifocal single system (SS), indomethacin in bone multifocal SS and vinblastine combined with low-dose prednisone (PDN) in multi-system (MS), PDN in pulmonary honey-combing disease (PHCD) and cladribine in central nervous system involvement. DAL-HX 83 and 90, LCH-I and LCH II were the pediatric protocols utilized over time. Response to treatment was defined as complete (CR) or intermediate (IR). Persistence of the symptoms and/or appearance of new lesions were defined no response (NR). Progression was considered the appearance of symptoms and/or new lesions after initial response. One-hundred-thirty-one LCH pts (females 72, males 59) with a median age at diagnosis of 36 years (range 18 - 71) were considered. Median follow up was 43 months (range 12 - 330). One-hundred-seven patients were managed according to the GIMEMA LCH 2001 guidelines, 16 of them previously treated with a pediatric protocol. Pulmonary and/or oral involvements were identified in 31/107 (29%) and 12/107 (11%) patients, respectively, 5/16 (31%) and 3/16 (19%), respectively, of previously treated asymptomatic patients. Ninety-one newly diagnosed patients (median age at diagnosis: 36 years) were treated according to the GIMEMA LCH 2001 guidelines and 40 (median age at diagnosis: 33 years) were managed with pediatric protocols. All patients treated with the GIMEMA LCH 2001 were evaluable for response. In particular, all patients with SS-LCH achieved a response (100%), that was complete in 20/26 (76.9%) unifocal-SS and in 10/14 (71.4%) multifocal-SS. All but one patient with MS-LCH reached a response that was complete in 22/45 (48.9%). Of 6 pts with PHCD, 5 had a IR and one a CR. No pt presented CNS involvement at initial diagnosis. Thirty-nine of 40 pts managed with pediatric protocols were evaluable for response. All 13 pts with SS-LCH had a response that was complete in 6 (46.1%). Among 26 patients with MS-LCH, 3 of them with organ risk involvement achieved a response, that was complete in 1, while among 23 patients without organ risk, 12 (52.2%), 8 (34.8%) and 3 (13%) had a CR, IR and NR, respectively. Overall, 12 patients were lost to follow-up. Disease progression was recorded in 47/95 pts (49.5%) after a median time of 19 months (range: 6-147 months). The progression-free survival at 43 months was significantly better for patients treated according to the GIMEMA LCH 2001 guidelines compared to those managed with pediatric protocols, 67% (IC95% 53.14 - 80.86%) vs 48% (IC95% 31.37 - 64.63%), respectively (p 0.005). Overall, 7 deaths were recorded, 5 in patients treated with the pediatric protocols. The overall survival at 43 months, was similar in patients managed with the GIMEMA LCH 2001 guidelines and in those treated with pediatric protocols (97.9%, CI 95%: 93.75% - 100% and 97.3%, (IC95% 91.96% - 100%). BRAF V600E mutation was found in 13/35 (37%) evaluable cases. No differences in response and outcome between BRAFV600E-mutated patients and those not-mutated were found. Our experience in a large cohort of LCH adults shows that a multidisciplinary approach is useful in identifying organ involvement in adults, including those asymptomatic. This is critical for an adequate treatment. Moreover, guidelines specific for adults with LCH proved efficacy in improving the outcome in this category of patients. Disclosures No relevant conflicts of interest to declare.

Imatinib mesylate (IM) has demonstrated to be highly effective in children with chronic myeloid leukemia (CML). The main issues remain the long-term side effects in pre-pubertal children and the poor compliance in adolescents. The aims of this study were: a) to evaluate the feasibility and efficacy of IM given intermittently to molecular responder (MR) CML children in chronic phase (CP), b) to reduce the long-term side effects of MR patients (pts) who started IM in pre-pubertal age, c) to improve compliance of poorly compliant adolescents in major MR (MMR). Among CP-CML pts aged Fifteen of 58 CP-CML pts diagnosed between March 2001 and June 2015 received IM given intermittently for a median of 40 months(range: 14-86). Before starting int-IM, 5 pts had been in persistent MR4.5-MR5 for a median of 39 months (Group I), 4 pts had been in MR for a median of 28.5 months and had been suffering from long-term side effects (Group II), and 6 pts had been in MMR and were poorly compliant to treatment (Group III). Features and outcome of the 15 pts are shown in Table 1. Group I: 3/5 pts in MR4.5-MR5 discontinued int-IM after 16, 34 and 36 months and remain in continuous MR after 89, 90 and 107 months; 2 pts are still receiving int-IM for 14 and 36 months, respectively. Group II: 2/4 pts achieved a deeper MR (1 from MR4 to MR4.5 and 1 from MR4.5 to MR5) while on int-IM. However, 3 pts lost the response after 24 (cytogenetic relapse), 40 and 77 (molecular) months from the beginning of int-IM; all of them were successfully treated with IM given continuously. One pt is still receiving int-IM. Group III: 2/6 pts achieved a deeper MR (1 from MR3 to MR4.5 and 1 from MR3 to MR4) while on int-IM. However, 5/6 patients lost their response after a median time of 69 months (57-74). Four of them were treated with IM given continuously and 1 received dasatinib; all obtained a response. One, who achieved a deeper MR (MR3 to MR4), is still on int-IM after 86 months. Overall, 4/15 (26.7%) pts improved their molecular response while on int-IM and 3/15 pts (20%) successfully discontinued treatment. On the other hand, 8/15 pts (53.3%) failed int-IM after a median of 63 months (range 24-77) from the beginning (6 pts lost MMR and 2 pts had a cytogenetic relapse). No pt underwent a stem cell transplantation. Long-term side effects (bone metabolism, growth rate and pubertal development) progressively improved during IM given intermittently. At the last follow-up, 6 pts (4 MR5, 1 MR4.5, 1 MR3) are still receiving int-IM, 5 (3 MR4, 2 MR2) are receiving continuous IM, 3 (MR4.5-MR5) are treatment-free and 1 (MR3) is being treated with dasatinib. All patients are alive at a median time from diagnosis of 151 months (range 52-266). Our experience suggests that an intermittent schedule of IM given 3 weeks a month could be an effective strategy before stopping IM in CP-CML children in persistent deep MR. Moreover, this approach is capable of improving the molecular response in poor compliant pts and is useful to reduce IM-related long-term side effects. The relatively high number of relapses in group III (5/6, 83%) is indicative of its poor efficacy in pts not compliant to IM given continuously. Based on these data, a prospective cooperative study has been planned. Disclosures Malaspina: Sapienza University, Rome: Other: Resident in Hematology. Rizzo:Sapienza University, Rome: Other: Resident in Hematology. Locatelli:bluebird bio: Consultancy; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Foà:CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; NOVARTIS: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau.