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Abstract 3010FN2 Background: There is a need to improve the conditioning regimens for allogeneic HSCT, both reducing the regimen related toxicity and improving the anti-leukemic effect. The myeloablative (MA) regimen consisting in intravenous (iv) busulfan (BU) with fludarabine (F) might be a better option than the conventional BU-CY (Cyclophosphamide) combination, since BU and F act synergistically against leukemia cell lines and previous studies with iv BU-F conditioning have reported an improved safety profile over BU-CY. Objective: We aimed to evaluate the efficacy and safety of the MA BU-F regimen, delivering iv BU in a one-daily dose after F infusion, since previous pharmacologic and clinical data supported its safety compared with the standard four-daily doses in the HLA identical sibling allogeneic HSCT setting. Patients: One hundred thirty seven consecutive adult patients with myeloid malignancies from nine Spanish institutions were recruited from 2005 to 2011. They had a median age of 47 years (range 19–74) and 60% were males. Diagnosis were AML: 80 (58.4%), AML secondary to MDS: 24 (17.5%), MDS: 23 (16.8%) and MPD: 10 (7.3%). At HSCT, the disease stage was 1st CR or untreated in 85 (62%) and more advanced stage in 52 (38%) cases. Patients having Karnofsky < 90% and Sorror CI >1 accounted for 11.7% and 38.3%. The conditioning regimen consisted in F, 40 mg/m2 daily for 4 days (total dose 160 mg/m2) followed by BU, one-daily IV 3.2 mg/kg infusion (total dose 12.8 mg/kg). GVHD prophylaxis consisted in cyclosporine and methotrexate. HSC infusion and post-transplant supportive measures and follow-up were made according each institution policies. Results: Donor graft source was peripheral blood (PB) in 93 (67.9%) and bone marrow (BM) in 44 (32.1%) cases. Median CD34+ cells infused were 4.5 millions/kg (range 0.6–17.8). All but one patient engrafted, with a median of 15 days (range 8–49) to >0.5 ×10E9 PMN/L and 13 days (range 7–149) to >20 ×10E9 platelets/L. The most frequent toxicity was mucositis, which was grade >1, in 68.8% cases. Three patients had hepatic SOS grade >1, and all of them resolved. Median hospitalization time was 30 days (range 17–114). Acute GVHD grade 2–4 incidence was 25% with a median of 32 days (range 12–87) to GVHD onset. The day-100 mortality was 4.8%. The chronic GVHD incidence in 114 patients at risk is 61.4%, with 37.7% of cases in extended form. At the time of this analysis, the median follow-up is 12 months (range 1–74). Crude survival data showed 106 (77.4%) patients remaining alive and 106 (77.4%) relapse free. Overall, 31 patients have died, 19 relapse-related (13.9%) and 12 (8.8%) due to transplant related mortality. Actuarial survival at 12 months is 79.4% and disease free survival is 71.3% in the whole series. Kaplan-Meier analysis showed that advanced age, comorbidities or advanced disease status at HSCT did not predict an inferior outcome. In conclusion, in the HLA identical sibling allogeneic HSCT setting, the BU-F regimen provides an adequate control of myeloid malignancies, with low regimen related toxicity and both reduced day-100 and non-relapse related mortality. Disclosures: Lahuerta: Janssen: Honoraria; Celgene: Honoraria.

Although oil-immersed power transformers generally use mineral oil as insulation and cooling fluid, this liquid does not meet the new technical requirements of dielectric fluids such as high biodegradability, non-toxicity and high safety. For these reasons, natural and synthetic esters as alternative to mineral oil have increased their utilization in some transformers installations. Despite the fact that there are several works that have demonstrated the suitability of these insulation fluids from the point of view of their stability, dielectric and thermal properties, there are very few works focused on the study of the effects of these liquids on impregnation process. The aim of this work is provide information about the behavior of different rigid insulation materials, not studied until now, during the impregnation process in a synthetic ester compared with a mineral oil. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 823969-BIOTRAFO

Background: Adults with high risk ALL features at diagnosis, slow responders or with recurrent disease have a poor outcome with standard chemotherapy and are considered for unrelated transplants in most centers if a matched sibling donor is not available. Unrelated cord blood (UCB) has emerged as an option for unrelated transplant in adult patients. Aim of the study: to compare the outcome of adult patients with unrelated transplant for poor prognosis ALL based on the hematopoietic source used for transplant. Patients and Methods: One hundred and forty- nine adult patients (median 29 years [15–59], 90M/59F) with poor prognosis ALL received an unrelated transplant in 13 Spanish institutions from 2000 to 2007. Patients in 1st CR at transplant met at least one adverse prognostic factor (adverse cytogenetics, hyperleukocytosis or a slow-responder). ALL was of precursor B lineage in 111 (74%), T-cell lineage in 28 (19%) and undetermined lineage in 10 (7%) patients. ALL was in 1st CR in 81 (54%) patients, in 2nd CR in 37 (25%), in 3rd CR in 11 (7%) and overt disease in 20 (13 %) patients. Both groups were comparable for the main clinical and biologic ALL features except for patients with more overt disease in UCB transplant group. Conditioning therapy consisted on TBI-CY in 68 (46%), BU-CY in 9 (6%), Thiotepa- BU-CY/FLU in 60 (40%) patients (all of them UCB transplants) and other regimens in 12 (8%) patients (6 of them were non-myeloablative). The source of hematopoietic progenitors was UCB in 62 (41%), mobilized PB in 41 (28%) and BM in 46 (31%) patients. HLA compatibility requirements for selecting unrelated donors (BM and mobilized PB) were 7–8 out of 8 allelic identities, and for UCB were 4–6 out of 6 A / B antigenic and DR allelic identities. Results: Acute GVHD was most frequent after PBSCT and BMT thanin UCBT. There was no significant difference for limited and extensive chronic GVHD between UCBT and PBSCT/BMT. The median follow-up was 16 months (0.3–101.4). DFS estimated at 5 years for patients transplanted with any source was not significantly better in transplants in 1st CR versus 2nd CR or more advanced disease (median 12 [2–22] vs 5 [2–9], p=0.106). There was no statistical difference in OS or DFS at 5 years between UCB and PBSCT/BMT). TRM was significantly lower in UCB transplants (p=0.021). The relapse probability was 17% for the PBSCT/BMT versus 29% for UCBT (p=0.088). The use of TBI as conditioning therapy was not associated with a lower relapse rate. 5y-OS (95%CI) Median OS (month, 95%CI) 5y-DFS (95%CI) Median DFS (month, 95%CI) 5y-TRM (95%CI) *p=0.021 Whole series 26% (17–35) 10 (4–17) 21% (13–29) 7 (3–11) 54% (44–64) PBSCT/BMT 22% (11–33) 9 (2–17) 21% (11–31) 5 (2–9) 63% (50–76)* UCBT 33% (18–48) 15 (7–22) 22% (8–36) 9 (1–17) 39% (25–53)* 1st CR ALL 30% (16–44) 12 (0–29) 24% (11–37) 12 (2–22) 57% (43–71) PBSCT/BMT 27% (9–45) 27 (2–51) 24% (8–40) 12 (2–22) 63% (44–82) UCBT 35% (14–56) 10 (0–23) 24% (4–44) 10 (0–26) 50% (31–69) GVHD was the main cause of death for unrelated PBSCT/BMT in contrast with infection and relapse for UCBT (p=0.001). Conclusions: UCB transplant and unrelated PBSCT/ BMT are equivalent options for poor prognosis adult ALL patients without a sibling donor. However, all modalities are associated with high transplant related mortality.

INTRODUCTION: Death is as a common cause of remission induction failure in patients with acute myeloid leukemia (AML), mainly due to hemorrhage and infection. The relative incidence and chronology of each of these categories of induction failure, as well as their prognostic factors, have been investigated critically and in detail in rare studies only. OBJECTIVES: We report the incidence, chronology, and prognostic factors for induction death, analyzing separately hemorrhagic and infectious death, in a large series of 946 patients with AML who received induction therapy in a single institution over the last 30 years. PATIENTS AND METHODS: Adult patients were consecutively diagnosed of AML and started first induction chemotherapy in our institution. AML was classified according to the FAB criteria. Induction therapy consisted of the classic combination of cytarabine and anthracyclines (with or without a third agent) in 50% of patients, cytarabine plus adriamicine and thioguanine or vincristine in 17%, ATRA with chemotherapy in 9%, monochemotherapy with anthracycline in 7%, high dose cytarabine in 7%, and other regimens in 10%. Causes of induction death include the following categories: Infection, when death was due to a clinical, radiological or microbiologically documented infection, Hemorrhage, when a major bleeding occured in a vital organ (central nervous system, lungs). Gastrointestinal hemorrhage required massive melena or hematemesis accompanied by fall in blood pressure, and Other, i.e., any other cause not classified as infection or hemorrhage. RESULTS: From 1977 to 2007, 946 consecutive patients with diagnosis of AML received induction chemotherapy, 24% in the period 1 (1977–1986), 28% in the period 2 (1987–1993), 28% in the period 3 (1994–2000), and 20% in the period 4 (2001–2007). Median age was 55 years (range 13–83 years). One hundred and sixty-seven patients (18%) had antecedents of myelodysplastic/myeloprolipherative disease (10%) or other neoplasia (8%). Two hundred and thirty-seven patients (25%) died during induction therapy, 13% due to infection, 7% due to hemorrhage, 2% due to hemorrhage and infection, and 3% due to other causes. The induction mortality rates decreased gradually over the 4 periods (31% vs 24% vs 18% vs 18%), due to reduction of both hemorrhagic and non-hemorrhagic deaths. Overall, 42% of hemorrhagic deaths occurred within the first 10 days of induction therapy, whereas 86% of infectious deaths occurred after 10 days. In multivariate analysis, the following characteristics had an unfavorable impact on overall induction mortality: age >60 years, WBC >50x109/L, Quick index 1, and albumin serum levels 50 years, AML secondary to neoplasia, ECOG >1, and fever at presentation. The following factors were associated with hemorrhagic mortality: WBC >50x109/L, FAB-M3, age >60 years, de novo AML, and ECOG >1. CONCLUSIONS: The main causes of induction death in AML patients, infection and hemorrhage, shows a different chronologic pattern and can be separately predicted by their own specific prognostic factors.