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[Resumen] Una de las principales preocupaciones sobre la regeneración de aguas municipales residuales es la eliminación de microcontaminantes, como plaguicidas o compuestos farmacéuticos, junto con microorganismos perjudiciales. Una metodología para llevar a cabo dicha eliminación es mediante la combinación de sistemas de nanofiltración apropiados con sistemas avanzados de oxidación. Este trabajo se centra en mejorar el proceso de nanofiltración desde el punto de vista del control automático, con el fin de contribuir a la posible industrialización del proceso para la aplicación de separación y pre-concentración de microcontaminantes de efluentes procedentes de plantas de tratamiento de aguas residuales municipales. Al tratarse de un sistema multivariable con interacción, se ha aplicado la técnica de desacoplamiento invertido en simulación, mejorando la calidad del control en un 18% frente al caso sin desacoplo. [Abstract] The removal of microcontaminants, such as pharmaceuticals compounds or pesticides, which is one of the main concerns in municipal wastewater regeneration jointly with harmful microorganisms, can be performed through the combination of appropriate nanofiltration (NF) systems with advanced oxidation post-treatments. This work analyzes the optimization of the NF process operation to contribute to the industrialization of this application for the separation and pre-concentration of microcontaminants from municipal wastewater treatment plant effluents. It consists in a multivariable system with coupling between its variables, applying the inverted decoupling method, the control perfomance has been improved 18% with respect to the case with no decoupler, in simulation. Este trabajo ha sido desarrollado en el marco del proyecto EU-H2020 SFERA-III (GA 823802).

The effect of different times of Fe:Ethylenediamine-N, N'-disuccinic acid (EDDS) dosing and H

Background Targeted therapy with Tyrosine-Kinase-Inhibitors (TKIs) totally modified the course of treatment of Chronic Myeloid Leukemia (CML). The objectives and the needs of treatment have been modified during the last years and the discontinuation of therapy is now a feasible aim. However, a lot of biological data acquired in the last twenty years, showed that degree and mechanisms of Leukemic Stem Cells (LSCs) clearance during TKI treatment are not clearly established as well as the predictive criteria for a stable and prolonged Treatment Free Remission (TFR). The multicentre, prospective, single-arm PhilosoPhi34 study (EudraCT: 2012-005062-34) was designed by the Rete Ematologica Lombarda (REL), to verify the in-vivo activity and time-course of first-line Nilotinib (NIL) therapy on Bone Marrow (BM) CD34+/lin-Ph+ cells clearance. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells at diagnosis and at 12 months (mos) of treatment, for the first 30 evaluable pts, was included. Preliminary GEP data suggested a correlation between different NFKBIA expression at diagnosis and at 12 mos and the achievement of a deeper Molecular Response (MR) (Pungolino et al, AJH 2018). We report here some results of GEP analysis on all enrolled evaluable pts and their possible correlation with clinical data. Methods BM cells were collected and stored at diagnosis and at 12 mos of treatment. CD34+/lin- cells were purified with a Diamond CD34 Isolation Kit Miltenyi (97% of purity). For GEP analysis we used Affymetrix HG-U133 Plus 2.0 microarray and Genechip platform (Affymetrix) and the Affymetrix GeneChip Scanner 3000. Data was pre-processed and normalized using the Robust Multi-array Average (RMA) algorithm. The Significant Analysis of Microarrays (SAM) was used to identify genes with statistically significant changes in expression. P-values were corrected for multiple testing using false discovery rate, for differentially expressed genes confirmation. We chose to analyse different expression of NFKBIA (the inhibitor of NF-kB onco-gene) in order to confirm the preliminary data reported on the first 30 analysed pts. Pts were monitored according to ELN-recommendation. Biological data were correlated with MR at 3, 12 and 36 mos of therapy. We use Fishers test to compare unbalanced group. Results Out of the 87 enrolled pts, 80 completed the first 12 mos of treatment and 78 (1 failure and 77 CCyR) were evaluable for GEP analysis. We observed 2726 genes symbol differentially expressed of which 1868 are coding genes. Among these, JAK-2 showed a down regulation at 12 mos (p: .024). JAK-2 expression ranged from 2.62 to 4.95 at diagnosis and from 1.48 to 5.58 at 12 mos. Only 26/78 pts increased JAK-2 expression that was > 4 in 1/26 pts, at diagnosis; 2/26 (7.69%) pts showed a H Sokal. Other 52/78 pts decreased JAK-2 expression that was ≥ 4 in 21/52 pts, at diagnosis; 10/52 (19.23%) pts and 6/21 (28,57%) pts showed a H Sokal. Similarly, when we compared low JAK-2 expression (< 3.5) vs vary high expression (≥ 4) 2/21 vs 6/22 pts had H Sokal (9.52% vs 27.27%; p: .0057). Considering the role of JAK-2 and NFKBIA in cell regulation and survival, we evaluated how the combination of their different expression impact on MR (i.e. NFKBIA increased expression/JAK-2 decreased expression vs NFKBIA decreased expression/JAK-2 increased expression). Data are reported in Table 1 and 2. Conclusion GEP analysis showed a down regulation of JAK-2 expression after 12 mos of first line NIL treatment, in 78 early chronic phase CML pts. Data suggest that high expression of JAK-2, at diagnosis, correlate with H Sokal score. However, H Sokal pts with a JAK-2 down regulation, obtain during treatment similar MR compared to L Sokal pts. Additionally, the study confirms our preliminary observation on 30 pts , concerning the role of NKBIA up - regulation in increasing percentage of earlier and deeper MR . The better condition of NFKBIA and JAK-2 expression (up regulation of NFKBIA and down regulation of JAK-2) is associated with a higher percentage of early MR3 and optimal responses over time, despite the higher number of H Sokal pts in this group. A study with NIL as first line treatment combined with low dose of JAK-2 inhibitor and a natural inhibitor of NF-kB (such as curcuma), during the first year of treatment, to increase the deeper MR rate and the probability of TFR is warrented. Disclosures Rossi: Sandoz: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Teva: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Novartis: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

BACKGROUND: In allogeneic hematopoietic stem cell (HSC) transplantation, the collection of an appropriate number of HSCs while maintaining a high level of safety for healthy donors is fundamental. Inadequate HSC mobilization can be seen with the standard use of granulocyte-colony-stimulating (G-CSF). Plerixafor (PL) is a chemokine receptor CXC Type 4-stromal-derived factor 1 inhibitor; its HSC-mobilizing properties are synergistic with G-CSF in poor mobilizing patients. The use of PL as adjuvant or alternative to G-CSF in healthy donors has shown a good safety profile but is so far off-label. STUDY DESIGN AND METHODS: We report 10 healthy HSC donors treated with PL because of insufficient response to G-CSF alone or contraindication to G-CSF. Eight donors did not mobilize enough CD34+ cells with G-CSF alone because poor mobilizers or because insufficient HSCs were harvested according to the clinical need of the patient; in two cases G-CSF administration and marrow harvest were unfeasible or contraindicated in the donor. RESULTS: The use of PL for mobilization increased the number of circulating CD34+ cells by 2.8-fold and the CD34+/kg collection by 3.0-fold. Only mild adverse events were reported (bone pain or discomfort) and not univocally attributable to PL. Rate of engraftment and graft-versus-host disease were similar to those seen in recipients of grafts from G-CSF only-mobilized donors. CONCLUSION: We exposed 10 allogeneic donors to mobilization with PL. PL was well tolerated in all cases and ensured procurement of an adequate graft for transplantation resulting in a normal hematopoietic engraftment.

The pilot-scale solar degradation of trimethoprim (TMP) in different water matrices (demineralized water: DW, simulated natural freshwater: SW; simulated wastewater: SWW; and real effluent: RE) was investigated in this study. DOC removal was lower in the case of SW compared to DW, which can be attributed to the presence of inorganic anions which may act as scavengers of the HO . Furthermore, the presence of organic carbon and higher salt content in SWW and RE led to lower mineralization per dose of hydrogen peroxide compared to DW and SW. Toxicity assays in SWW and RE were also performed indicating that toxicity is attributed to the compounds present in RE and their by-products formed during solar Fenton treatment and not to the intermediates formed by the oxidation of TMP. A large number of compounds generated by the photocatalytic transformation of TMP were identified by UPLC-QToF/MS. The degradation pathway revealed differences among the four matrices; however hydroxylation, demethylation and cleavage reactions were observed in all matrices. To the best of our knowledge this is the first time that TMP degradation products have been identified by adopting a solar Fenton process at a pilot-scale set-up, using four different aqueous matrices.

This work investigated the application of a solar driven advanced oxidation process (solar Fenton), for the degradation of the antibiotic ofloxacin (OFX) in various environmental matrices at a pilot-scale. All experiments were carried out in a compound parabolic collector pilot plant in the presence of doses of H2O2 (2.5mgL−1) and at an initial Fe2+ concentration of 2mgL−1. The water matrices used for the solar Fenton experiments were: demineralized water (DW), simulated natural freshwater (SW), simulated effluent from municipal wastewater treatment plant (SWW) and pre-treated real effluent from municipal wastewater treatment plant (RE) to which OFX had been spiked at 10mgL−1. Dissolved organic carbon removal was found to be dependent on the chemical composition of the water matrix. OFX mineralization was higher in DW (78.1%) than in SW (58.3%) at 12mgL−1 of H2O2 consumption, implying the complexation of iron or the scavenging of hydroxyl radicals by the inorganic ions present in SW. On the other hand, the presence of dissolved organic matter (DOM) in SWW and RE, led to lower mineralization per dose of H2O2 compared to DW and SW. The major transformation products (TPs) formed during the solar Fenton treatment of OFX, were elucidated using liquid chromatography–time of flight-mass spectrometry (LC–ToF-MS). The transformation of OFX proceeded through a defluorination reaction, accompanied by some degree of piperazine and quinolone substituent transformation while a hydroxylation mechanism occurred by attack of the hydroxyl radicals generated during the process leading to the formation of TPs in all the water matrices, seven of which were tentatively identified. The results obtained from the toxicity bioassays indicated that the toxicity originates from the DOM present in RE and its oxidation products formed during the photocatalytic treatment and not from the TPs resulted from the oxidation of OFX. •The pilot-scale solar Fenton degradation of ofloxacin was studied.•Mineralization was lower in the wastewater matrices due to the presence of organics.•Toxicity was found to originate from the oxidation of DOM present in the RE.•The transformation of OFX proceeded through the formation of seven intermediates.•The degradation pathway exhibited differences among the four matrices. 461-462 39 48

In this paper, we present pilot-scale solar Photo-Fenton and TiO2 treatment of a model compound (α-methylphenylglycine) dissolved in 500 mg/l concentration in water. Not only contaminant disappearance and mineralisation were evaluated, but also enhancement of biodegradability. The solar photoreactors, composed of 4.16 m2 of compound parabolic collectors, had a total volume of 82 l (44.6 l illuminated). Treatment was successful with both Advanced Oxidation Processes (AOPs) tested, but photo-Fenton was shown to be by far more efficient from the kinetic and practical point of view. To find out the conditions for biocompatibility using the AOPs as a pre-treatment, waste water after certain degradation time, unacclimated municipal sludge and mineral nutrients were placed together and evaluated by the Zahn-Wellens (Z-W) test. Biodegradability was enhanced (70% biodegradable) by both AOPs, but photo-Fenton was demonstrated to be more efficient, requiring a treatment time one order of magnitude shorter than TiO2. Hydrogen peroxide management for reduced consumption and elimination prior to discharging water to the biotreatment step is also discussed in detail.

Test results for a designed and installed hybrid photocatalytic–photovoltaic system (HPPS) are presented in this paper. The HPPS consists of one device with dual functions: The photocatalytic system uses UV radiation to promote degradation of organic pollutants, and beside it absorbs the IR radiation. The photovoltaic (PV) system converts the visible radiation into electricity, which can either be used directly by the recirculation pump or stored in a battery for other purposes. The suggested design aims to achieve an autonomous, environmentally friendly method for the treatment of biorecalcitrant pollutants. Two prototypes were erected: HPPSP, using Plexiglas and HPPSG using commercial glass. Both were tested outdoors to determine their impact on photovoltaic power production. Test results showed that PV power diminished to 14% and 22% for HPPSG and HPPSP respectively, compared to a PV panel alone.

This work aims to evaluate the applicability of EDDS (ethylenediamine-N,N'-disuccinic acid) as an iron chelating agent for photo-Fenton treatment of municipal wastewater spiked with organic contaminants at near-neutral pH. A series of laboratory scale experiments are conducted under simulated sunlight in accordance with a central composite experimental design in order to define the most favorable conditions in terms of initial iron concentration (maintaining a molar ratio 1:2 of Fe:EDDS), H2O2 and pH. The system is evaluated in terms of degradation efficiency, H2O2 consumption and iron availability. The simulated system has been compared in terms of degradation efficiency with a 60 L compound parabolic collector (CPC), and significant correlation has been observed. An approach for estimating near-optimal regions of operability is also demonstrated. (C) 2015 Elsevier B.V. All rights reserved.

This study evaluates the use of the Fe(III)-EDDS complexing agent as an alternative to conventional acidic pH photo-Fenton for the treatment of the pesticide imidacloprid in natural water. The main objective is to estimate whether Fe(III)-EDDS is a viable alternative when treating waters containing high concentrations of contaminants. To this end, the mode of action of Fe(III)-EDDS is examined in the presence of carbonates, at different aeration conditions and at different temperatures. The role of HO2 center dot/O-2(center dot-) radical species and some aspects of the Fe(III)-EDDS complexation mechanism are discussed. Degradation kinetics and toxicities of generated intermediates are compared between Fe(III)-EDDS and conventional photo-Fenton treatment. An overview of the benefits and limitations of the process is presented. (C) 2015 Elsevier B.V. All rights reserved.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.

Background Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder which molecular base is represented by the bcr-abl fusion gene, encoding for the constitutionally activated BCR-ABL tirosine-kinase. Three Tirosin-Kinase Inhibitors (TKI) are approved for first line treatment: Imatinib (IM) and the second generation (2G) TKI Nilotinib (NIL) and Dasatinib. 2G TKI are known to provide faster and deeper molecular responses (MR) compared to Imatinib, but serious toxicities may hamper long term treatment with these molecules. Furthermore, 2G TKI were usually employed as second line after IM failure, while the inverse sequence from second to first generation TKI (like an induction-maintenance model) has not been explored yet. We used this schedule in a small group of patients in the PhilosoPhi34 study (EudraCT: 2012-005062-34), a clinical trial designed by the REL (Rete Ematologica Lombarda) cooperative group. This study was composed by three consecutive phases: a Recruitment Phase, a Core Phase (CP) in which patients received NIL 300 mg BID for 12 month (mos), and an Observational Phase (OP), restricted for patients who obtained at least complete cytogenetic response at the end of the CP. During OP, treatment choice was up to the physician and any TKI approved for first line treatment could be used, including IM. In 2017 we presented preliminary data showing that a 12-mos-NIL treatment followed by IM appears as a safe and effective choice for first line therapy in chronic phase CML. Fluctuations in BCR/ABL ratio were similar between IM and NIL treated pts, and the probability of loss of MR4 or MR3 was the same in the two groups; furthermore, despite fluctuations, MR was maintained or improved over time in IM subgroup. Our purpose is to verify these data after 24 mos follow up (FU) at the end of OP. Methods We analyze PhilosoPhi34 database; MR is reported at 3, 6 and 12 mos during the CP and every 6 mos during the OP. The last pt completed the 24 mos of OP in June 2018. Database is still open, evaluations ongoing, and some data can be missing yet: our preliminary observations concern pts with available data of 24 mos OP. Results Seventy-nine pts started the OP. Fourteen pts switched to IM during the OP (Table 1) due to high cardiovascular risk or grade 1-2 chronic AEs . Only 11 pts started IM since the beginning of OP, and we consider these pts in our analysis. Sokal score was high in 2 pts (18%), intermediate in 5 (45.5%), low in 4 (36.5%). At the beginning of OP, 6 pts had a MR ≥ 4 (54.5%), 5 had MR3 (45.5%). At 12 mos of the OP, 7 had MR ≥ 4, 3 had MR3 and 1 had lost MR3 with PCR 0.192%IS (1/5, 20%). At 24 mos of the OP, 9 had MR ≥ 4 (81,8%), and 2 had MR3. Notably, none of pts lost MMR; 2/3 pts(66%) improved response from MR 3 to MR 4 and the pt who transiently lost MMR at 12 mos, recovered it at 24. Sixty-four pts maintained 2G TKI: 62 NIL, 2 other TKI (not considered for analysis). Of them, 4 were lost during this phase: 2 within the first year of OP, other 2 within 12 and 24 mos of OP. In the NIL group, Sokal score was high in 10 pts (16.6%), intermediate in 19 (31.6%) and low in 31 (51.6%). At the beginning of OP, 32 pts had MR ≥ 4 (51.6%), 21 had MR3 (33.8%) and 9 less than MR 3 (14.5%). Responses were improved over time: at 12 mos, 36 pts had MR ≥ 4 (60%), 20 had MR3 (33%) and 4 less than MR3 (6%). At 24 mos 46 pts had MR ≥ 4 (78%), 8 MR3 (13.5%) and 4 less than MR3 (8,5%), Among them, 1 pt experienced disease progression due to a mutation. In particular, during the second year of OP, 11 pts improved response from MR3 to MR ≥ 4(11/20, 55%). Discussion Our data show progressive MR improvement in both IM and NIL group. In particular, risk of loss of MMR is not increased in IM group. More data, more balanced groups and a longer FU are necessary to further confirmations, but after three years of FU, we consider this combination of NIL-followed-by-IM a possible strategy for first line treatment in chronic phase CML, in particular for pts with cardiovascular risk factors. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Chronic myeloid leukemia (CML) is a disease of stemming from genetic damage to a hematopoietic stem cell. Despite nilotinib being a very effective drug for the treatment of CML, drug resistance can emerge. In the contest of the REL-PhilosoPhi34 study on behalf of the Rete Ematologica Lombarda, we performed an exploratory study aimed to identify the gene expression signature of bone marrow (BM) CD34+/lin- cells of CML patients at diagnosis as well as after 12 months of nilotinib to investigate the genes and pathways responsible for the response or resistance to nilotinib. Microarray experiments were performed using the latest generation Affymetrix GeneChip HTA 2.0 to further investigate genomic complexity. The study was developed in two steps as follows: In the first step we analyzed 30 CML patients and from the comparison between the BM CD34+/lin- cell counts from each patient at diagnosis and after 3 and 6 months of nilotinib, patients were divided into 2 classes: class 1 (n=24) showed highly reduced levels of CD34+/lin- cells while class 2 (n=6) demonstrated increasing levels of CD34+/lin- cells after 3 and 6 months of nilotinib, respectively (Fig.1). The 30 patients can be divided into 6 groups showing different patterns of CD34+/lin- cellularity (Figure 1). Data was preprocessed and normalized using Robust Multi-array Average (RMA) algorithm. The Significant Analysis of Microarrays (SAM) was used to identify genes with statistically significant changes in expression in CML patients. P-values were corrected for multiple testing using false discovery rate. No transcripts were selected as differentially expressed using this threshold. However, if a nominal significance level alpha equal to 0.05 is adopted together with a fold-change threshold equal to 2 (absolute value), 56 transcripts were selected in the comparison between the 2 groups of CML patients. Among them, we focused on NFKBIAgene which was over expressed in class 1 compared to class 2.NFKBIA is involved in 68 pathways regulating apoptosis (PI3K,NF-kB) and encodes IkBα protein belonging to the NF-kB pathway which is a potential downstream target of BCR-ABL1 due to its role in regulating cell survival and proliferation. Of note, 31/56 transcripts are located on chromosome 15 suggesting that this region could be crucial for transcriptional regulation of CML correlated to nilotinib response. The second step analyzed the GEP of CD34+/lin- cells of 8 patients at diagnosis (class 1) vs. the same 8 patients after 12 months of nilotinib (class 2) to investigate the gene expression changes and the pathways induced by nilotinib treatment. Data was preprocessed and analyzed as described above. 247 probes (corresponding to 51 genes and 180 non-annotated transcripts) were selected with a p-value lower than 0.05 after multiple testing correction and using a fold-change threshold equal to 3 (absolute value). Functional enrichment analysis was performed using DAVID and highlighted the following pathways and genes: ¯ Defense response and immune system: CAMP, CRISP3, CYBB, RGS1, CEACAM8, LTF (cell growth and differentiation), MNDA and HP (positive regulation of apoptosis) were over expressed in class 2 with high fold changes of 7.65, 9.95, 4.40, 3.47, 4.28, 3.61, 3.60, 3.95, respectively ¯ Transcriptional regulation and cell cycle: MMP8was under expressed in class 1 with the high fold change of 8,94 ¯ S100A12, S100A8, S100A9 (regulation of the cell cycle and differentiation) were over expressed in class 2 with the FC of 8.68, 3.96, 4.49, respectively ¯ RNA5S-ribosomal pseudogenes 310-311-312-313-314-315-316-317-320-363 were downregulated in class 2 ¯ 10 small-nuclear-RNAs and 11 small-nucleolar RNA were differently deregulated between the 2 classes ¯ APOC1, PLBD1 (lipid metabolism) were overexpressed and underexpressed in class 1, respectively In conclusion, this is the first study of GEP of CD34+/lin- cells with HTA 2.0 which demonstrated that 51 genes mostly involved in immune system, transcriptional regulation and cell cycle were significantly differently expressed from the comparison between CML patients at diagnosis and after 12 month of nilotinib. Ongoing studies are focused on examining the genetic and biologic mechanisms underlying nilotinib response or resistance to predict response or failure providing new insights into the molecular mechanisms in CML. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract 2385 Background. Allogeneic haemopoietic stem cell transplantation (HSCT) is the best therapeutic option for high-risk hematological disease (HRHD), particularly acute myeloid and lymphoblastic leukemia (AML/ALL). A widely application of HSCT is limited by lack of availability of a suitable donor for every candidate patients (pts). In order to offer a donor to every candidate pts, several centers had developed in the last decade alternative strategy of HSCT, such as umbilical cord blood (UCB) or family haploidentical HSCT (haplo-HSCT). With the aim to treat high-risk leukemia in the ideal appropriate time by allogeneic HSCT, we adopted a policy relying upon HLA typing at entry of every pts diagnosed with HRHD, followed, in absence of a MRD, by the prompt activation of the MUD search. Patients lacking a MRD or a MUD at the appropriate timing are proposed for haplo-HSCT. Methods. Here we report an intention-to-treat analysis of alternative donor HSCT at our Institution for pts diagnosed with high risk AML or ALL. Data were obtained from local institutional database. Results. Between Jan-2004 and July-2010 241 pts (median age 48y, r 15–72) with diagnosis of ALL (60 pts; median age 33y, r 15–64; male 39) or AML (181 pts, median age 51y, r 19–72; male 83) were defined as “high risk status” and received an indication to HSCT according to EBMT (European Group for Blood and Marrow Transplantation) and Northern Italy Leukemia Group (NILG, www.nilg.it) recommendations. In the ALL group 3 pts died before proceed to HSCT, 5 pts are waiting for the identification of a donor. Overall, 52/60 (86%) pts underwent HSCT, the status of disease at transplant was of complete remission (CR) for 27 pts, persistence of disease (PD) for 25. In the AML group 6 pts died before proceed to HSCT, 15 pts are waiting for the identification of a donor. Overall, 160/181 (88%) pts underwent HSCT, the status of disease at transplant was of CR for 97 pts, PD 63. Overall 92 pts activated the research of a MUD, 42 proceed to transplant, 7 received a UCB, 26 received a haplo-HSCT due to absence of a suitable donor in the appropriate time frame or failure to met the criteria to engage a MUD donor. The median time from diagnosis to registry activation was 69 days (r 5–876), the median time from activation to transplant 84 days (r 28–348). In the group of pts in CR at transplant, 37 underwent HSCT from a MRD and 36 from a MUD, 4 pts received a UCB and 47 a haplo-HSCT. Seventy-two pts are alive and in CR at last follow-up, 3/72 after a second transplant from a different donor (haplo-HSCT) and 3/72 after chemotherapy and adoptive immunotherapy to treat hematological relapse. Fifty-two pts died and the causes of death were: relapse (27), infection-related (19), graft-versus-host-disease (GvHD; 5), acute myocardial infarction (1). In the group of pts in PD at transplant, 16 underwent HSCT from a MRD and 6 from a MUD, 3 pts received UCB and 63 a haplo-HSCT. Fifteen pts are alive, 14 in CR, 1 pts under adoptive immunotherapy; 1/14 pts received a second transplant from a different donor (haplo-HSCT) to treat hematological relapse. Seventy-three pts died and the causes of death were: relapse (43), infection (23), GvHD (7). Overall, the median survival is 382 days and the median follow-up for pts alive is 548 days. The 1-year overall survival (OS)/transplant related mortality (TRM)/relapse incidence (RI) are 50,76% 26,96% and 40% respectively. For pts transplanted in CR the 1y OS/TRM/RI are 77,2%, 20,01% and 25% respectively. The outcome analysis per donor source (MRD vs MUD vs haplo-HSCT) is comparable (p=ns). For pts transplanted in PD the 1y OS/TRM/RI are 19,7%, 41% and 67% respectively. The outcome analysis per donor source (MRD vs MUD vs haplo-HSCT) shows a trend of lower RI and TRM in the haplo-SCT vs MRD. Conclusion. The policy adopted provided an allogeneic HSCT in > 80% of candidate high-risk acute leukemia patients. No significant differences were registered in outcome for patients transplanted from matched-related, unrelated or family haploidentical donors. Further evaluation and a long-term follow-up will add important evaluation in term of long-term disease control and long-term toxicities. Disclosures: Bonini: MolMed: Consultancy. Bordignon: Molmed: Employment.

Abstract 2382 Background. Allogeneic transplantation of haemopoietic stem cells (allo-SCT) from an HLA- matched related (MRD) or unrelated donor (MUD) is a curative option for patients (pts) with high-risk haematological disease (HRHD). In the absence of a MRD or MUD, pts have been offered investigational transplant strategies such as umbilical cord blood (UCB) or family haploidentical SCT (haplo-SCT). In our Institution, all patients with HRHD are typed at entry; if a suitable MRD donor is missing a MUD search is promptly activated through the Bone Marrow Donors Worldwide Registry (BMDW). Our policy is to offer an haplo-SCT to adult pts lacking an MRD or MUD in order to adequately treat HRHD in the ideal appropriate time according to clinical indications for allo-SCT. This policy is based on our ongoing protocols for primary disease. Methods. Here we report the intention-to-treat (ITT) analysis of alternative donor transplantation at our Institution. Data were obtained from Institutional database; all HRHD patients were included in analysis. Results. Between Jan-2004 and July-2010, 410 pts (100% of the following ITT analysis; median age 48y, range 15–76, 91 pts over-60y; male 264) received indication to allo-SCT according to EBMT recommendations. The majority of pts presented with a diagnosis of acute leukaemia (15% lymphoblastic, 45% myeloid), while 12% presented with non Hodgkin lymphoma, 8% myelodysplastic syndrome, 6% Hodgkin disease, 5% multiple myeloma, 2% chronic myeloid leukaemia, 2% chronic lymphocytic leukaemia, 2% severe aplastic anaemia, 1% primary myelofibrosis, 2% others. Eighty-nine pts (22%) received a transplant from a MRD; 190 pts (46%) activated an MUD search in the BMDW registry; 84 pts (20% of total pts, 44% of MUD searching) received a MUD transplant; 42 pts (10%-21%) received an haplo-SCT due to lacking of a suitable MUD in the appropriate timing according to disease status, or absence of suitable criteria to engage a MUD donor; 11 pts (3%-6%) received a UCB if lacking a suitable haplo donor. Overall, 149 pts received an haplo-SCT (36%): 42 after BMDW research, 107 up-front. Twenty-one pts died before receiving a transplant (5%), 37 (9%) are still searching for a suitable donor and an eligible donor is under final evaluation for 19 pts (5%). One-hundred-fifty pts underwent transplant in complete remission (CR), 12 in early phase, 9 in very-good-partial remission (VGPR), 7 in partial response (PR), while 155 were in progression of disease (PD). The median time from diagnosis to transplant was 165 days, the median time from MUD search to transplant 103 days (range 28–824 days). The overall survival (OS) analysis in intention to treat is 51% at 1 year, 39% at 3y; the 1y and the 3y OS for pts transplanted in CR/early phase/VGPR are 74% and 57% respectively, for the pts transplanted in PR/PD 29% and 21% (p At last evaluation 149 pts are alive, with a median follow-up of 802,5 days (range 2–2315); 93/149 received transplant in CR, 10 in early phase, 6 in VGPR, 3 in PR, 37 in PD. Twenty out of 149 experienced disease relapse and were rescue with salvage treatment and adoptive immunotherapy in 15 cases, while 5 pts received a second transplant from a different donor. Up to 155 pts transplanted in PD, 37 (24%) are alive with a median follow-up of 499 days, of these 22 pts received a haplo-SCT, 8 MUD, 6 MRD, 1 UCB. The median follow-up for pts dead is of 118 days (range 2–2315), the cause of death were disease relapse (53,26%), graft-versus-host-disease (8,7%), infection (31,5%), multi organ failure (3,8%), cardiovascular disease (1,09%), haemorrhage (1,63%). Conclusion. In ITT analysis, 81% of overall pts candidate received an allo-SCT (59% from an alternative donor, 22% from a MRD) and the outcome achieved for pts transplanted in CR is comparable within the three major donor source (MRD – MUD – haplo-SCT). This result confirm the need to offer to every candidate pts a transplant option in the appropriate time, but also support the use of alternative donors, particularly haplo-SCT, in absence of an available MRD or MUD. The highly committed policy performed in the alternative-SCT setting and the implementation of an alternative donor option are essential prerequisite to obtain these results, offering to every candidate pts a concrete opportunity of treatment. Disclosures: Bordignon: Molmed: Employment.