ALBERT

Description: The main purpose of this study is to propose a visitor centric perspective that can support museums towards sustainability. The main premise of this study is due to a concept of economic and social sustainability of museums, defined as the possession of sufficient resources to maintain the existence of an organization, and achieve their goals in the future, ensuring a certain flow of visitors. A great number of museums are characterized by a low number of visits; therefore, in order to become sustainable, museums should pay attention to audience and its internal diversity. In this way, a cultural site can plan tailored strategies to increase the number of visits and re-visits and to achieve community support. For this reason it is necessary to understand the cultural needs of visitors, acquiring appropriate monitoring tools, such as qualitative and quantitative ones. Generally, quantitative analyses are more reliable and complete, even if they require a considerable number of observations for the reliability of the results. Moreover, qualitative analysis provides more in depth information, even if their data do not allow us to make generalizations. The qualitative and quantitative methods for the detection of satisfaction are usually used separately, but their integration may bring significant added value in terms of the wealth of information. This study follows the analysis of the potential of the integration of qualitative and quantitative analysis techniques customized with respect to different types of targets. The results of the experimentation performed on ethnographic museums shows a consistency of the results obtained by the two different tools that increase the capacity information of survey instruments.

Description: Energies, Vol. 11, Pages 155: Thermal and Electrical Characterization of a Semi-Transparent Dye-Sensitized Photovoltaic Module under Real Operating Conditions Energies doi: 10.3390/en11010155 Authors: Cristina Cornaro Ludovica Renzi Marco Pierro Aldo Di Carlo Alessandro Guglielmotti Dye-sensitized solar cell technology is having an important role in renewable energy research due to its features and low-cost manufacturing processes. Devices based on this technology appear very well suited for integration into glazing systems due to their characteristics of transparency, color tuning and manufacturing directly on glass substrates. Field data of thermal and electrical characteristics of dye-sensitized solar modules (DSM) are important since they can be used as input of building simulation models for the evaluation of their energy saving potential when integrated into buildings. However, still few studies in the literature provide this information. The study presented here aims to contribute to fill this lack providing a thermal and electrical characterization of a DSM in real operating conditions using a method developed in house. This method uses experimental data coming from test boxes exposed outdoor and dynamic simulation to provide thermal transmittance (U-value) and solar heat gain coefficient (SHGC) of a DSM prototype. The device exhibits a U-value of 3.6 W/m2·K, confirmed by an additional measurement carried on in the lab using a heat flux meter, and a SHGC of 0.2, value compliant with literature results. Electrical characterization shows an increase of module power with respect to temperature resulting DSM being suitable for integration in building facades.

Description: Despite the large prevalence in the population, possible factors responsible for the induction of atrial fibrillation (AF) events in susceptible individuals remain incompletely understood. We investigated the association between air pollution levels and emergency department admissions for AF in Rome. We conducted a 14 years’ time-series study to evaluate the association between the daily levels of air pollution (particulate matter, PM10 and PM2.5, and nitrogen dioxide, NO2) and the daily count of emergency accesses for AF (ICD-9 code: 427.31). We applied an over-dispersed conditional Poisson model to analyze the associations at different lags after controlling for time, influenza epidemics, holiday periods, temperature, and relative humidity. Additionally, we evaluated bi-pollutant models by including the other pollutant and the influence of several effect modifiers such as personal characteristics and pre-existing medical conditions. In the period of study, 79,892 individuals were admitted to the emergency departments of Rome hospitals because of AF (on average, 15.6 patients per day: min = 1, max = 36). Air pollution levels were associated with increased AF emergency visits within 24 h of exposure. Effect estimates ranged between 1.4% (0.7–2.3) for a 10 µg/m3 increase of PM10 to 3% (1.4–4.7) for a 10 µg/m3 increase of PM2.5 at lag 0–1 day. Those effects were higher in patients ≥75 years for all pollutants, male patients for PM10, and female patients for NO2. The presence of previous cardiovascular conditions, but not other effect modifiers, increase the pollution effects by 5–8% depending on the lag. This study found evidence that air pollution is associated with AF emergency visits in the short term.

Description: Introduction: Busulfan (Bu) is used in the conditioning regimen for hematopoietic stem cell transplantation (HSCT). Therapeutic drug monitoring (TDM) of Bu with subsequents adjustments doses based on a “target” therapeutic concentration may reduce toxicity after HSCT. Objectives: To evaluatethe impact of TDM of Bu and clinical outcomes in patients with acute leukemia that underwent to allogeneic matched related donor (MRD) and allogeneic matched unrelated donor (MUD) HSCT. Patients and methods: From January 2009 to January 2014, we prospectively analyzed 42 patients with diagnosis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) who underwent TDM of Bu (IV or oral) before transplantation (test dose) and TDM on 1st day of conditioning regimen. Samples were collected at 0, 30’, 60’ and subsequently every hour until 6 hours after administration of busulfan. The plasma was extracted by HPLC (High Performance Liquid Chromatography). All the patients that were submitted to TDM had a test dose 15 days to 48 hours before transplantion. The dose of Bu was adjusted during the first day of the conditioning regimen based on test dose. At the same time we analyzed 21 patients in the retrospective group who did not underwent TDM (from 2004 to 2010). Results: In the retrospective group (n=21), all of them underwent to MRD transplantation. Six (46.2%) were in first complete remission (CR1), 18(85.7%) patients received Bu and cyclophosphamide (BuCy) and the mean of age was 38 years (18-55 Yo). The median of CD34+ cells was 5.4 x 106/kg. The second group consisted by patients that received oral Bu (n= 21): 7 (33.3%) underwent to MUD transplantation, 14 (66.6%) to MRD transplantation, 8 (44.4%) patients were second complete remission (CR2), 4 (22.2%) had active disease status with a mean age of 32.7 years (14-58 Yo). Fifteen (71.4%) received BuCy and 16 (76.2%) received cells from peripheral blood. The median of CD34+ cells was 5.8 x106/kg. The median area under the curve (AUC) in 24 hours was 4950 μMol.min (3196.6- 8212 μMol.min). The third group was IV Bu (n= 21): 7 (33.3%) patients underwent MRD and 14 (66.6%) MUD transplantation, 7 (33.3%) patients were CR1, 7 (33.3%) had active disease or prior HSCT with a mean of age 52.7 years (20-74 Yo). The majority of patients received fludarabine and Bu (n=18; 85.7%) as conditioning and bone marrow was the main source. Immunosuppression was based on FK-506 and methotrexate (90.5% of patients). The median of AUC in 24 hours was 5690 μMol.min (3539.6- 8881.8 μMol.min). The cumulative incidence (CI) of sinusoidal obstructive syndrome (SOS) in the retrospective group and IV Bu were 9.5% for both, while in the group oral Bu it was at 19% (p = 0.566). The median AUC of Bu received during conditioning for those who died of SOS was lower in oral Bu than IV Bu (4872 uMol.min vs 5732 uMol.min respectively). The CI of acute graft-versus-host disease (aGVHD) at D+100 was 38.1% in the retrospective group, 40.6% in oral Bu and 42.9% in IV Bu. Chronic GVHD was 13.6% in oral Bu, 34% in IV Bu and 42.9% in the retrospective group (p = 0.142). The CI of relapse at D+100 was 19% in IV Bu, 4.8% in the retrospective group and oral Bu did not have this event. The IC of death at D+100 was 34.9% in group oral Bu, 9.5% in IV Bu and 14.3% in the retrospective (p = 0.102). The CI of relapse at 1.5 years was 35.8% in the IV Bu, 34.8% in oral Bu and 14.3% in the retrospective group. The CI of death at 1.5 years was 9.5% in group IV Bu, 53.5% in oral Bu and 34.3% in the retrospective (p = 0.015). Among patients who died until D+100, the median of AUC was 5732 μMol.min (5578.5-6818.5 μMol.min) during the conditioning for IV Bu and 4872 μMol.min (3448-8212 μMol.min) for oral Bu. The range between the AUC was large and there was no correlation with patients who died. Conclusion: In acute leukemia SOS had an impact on mortality at D+100 after HSCT (p

Description: After the introduction of tirosine-kinase inhibitor in chronic myeloid leukemia (CML) treatment, the quantification of the level BCR/ABL positive cells has become essential. Since 1993, our lab has been using a sensitivity qualitative nested RT-PCR assay. Due to the need of tumor cells quantification in CML, we developed, in 2004, a quantitative test by real time PCR. The question was to define whether the relative or absolute quantification was the best strategy. To answer this question our lab team standardized both methods and compared them. The real time PCR (RQ-PCR) was performed in Applied Biosystems® 7500 plataform with TaqMan® probes towards b2a2, b3a2 BCR-ABL transcript and BCR reference gene, in a non multiplex assay. Two separate RQ-PCR reactions were prepared for the BCR-ABL standard and BCR standard. 129 peripheral blood samples of CML patients were tested by both relative and absolute methods. Quality control samples were analyzed in every RQ-PCR run to monitor assay performance: NTC, positive and negative control. Relative Quantification is based on the expression levels of a target gene (BCR-ABL) versus a reference gene (BCR). This method determines the mRNA level of BCR-ABL gene across mutiple samples and expresses it relative to the levels of an internal control. A pool of c-DNA of 30 patients with untreated CML in chronic phase was used as an internal control (N Engl J Med, 2003, oct 9, 349–15). This method does not require standards with known concentrations and we used Pfaffl mathematical model to calculate the expression of a target gene in relation to a reference gene (Nucl Acid Res.2001; 29:2002–7). The relative expression ratio is calculated from the real time PCR efficiencies and the crossing point of an unknown sample versus a control: Ratio= E(target) ΔCt target (controlsample)/E(reference) ΔCt reference (control-sample) Absolute Quantification determines the input copy number of the BCR-ABL transcript, usually by relating the PCR signal to a standard curve. The standard curve was constructed using plasmids. Plasmids contaning a cDNA fragment of genes under analysis (b2a2, b3a2 BCR-ABL transcript and BCR gene) were prepared by PCR cloning (Branford S, Br J Haematol, 1999; 107:508–99). A 10-fold diluition series in the range of 106 to 10 copies was prepared for the BCR-ABL transcripts and BCR gene. The results were reported as a ratio of BCR-ABL/BCR % and were expressed relative to the median of BCR-ABL transcripts in the blood of 30 patients with untreated CML in chronic phase (baseline). Results: We performmed 129 blood samples of CML patients by both the relative and the absolute RQ-PCR. The results showed a positive correlation between relative and absolute values (r = 0.969 and p =0.000). Conclusion: The results of relative and absolute RQ-PCR methods were equivalent. Although the absolute method is more frequent in literature, the relative quantification presents more simply standardization, low contamination risk since it does not work with plasmids and results as safe as the absolute RQ-PCR.

Description: Abstract 1211 Poster Board I-233 Umbilical cord blood transplantation (UCBT) has extended the availability of allogeneic hematopoietic stem cell transplantation to patients without HLA identical donors, mainly for groups of patients with high frequency of rare haplotypes such as the Brazilian population. We evaluated 173 patients who received a single first UCBT in Brazil between with 1993 and 2009 for hematological malignancies from 13 transplant centers. Median age was 8 years (range 1-60) and 58% were male. Sixty-nine patients (40%) had acute lymphoblastic leukemia, 57 (33%) acute myelogenous leukemia, 23 (13%) myelodysplastic syndrome, 18 (10%) chronic myelogenous leukemia and 6 (4%) chronic lymphoid diseases (4 Hodgkin's lymphoma, 1 non-Hodgkin lymphoma and 1 chronic lymphocytic leukemia). Most patients (55%) were transplanted in advanced phases of their diseases. Based on antigen-level HLA-A and -B and allele-level HLA-DRB1 typing, 64 patients (52%) received a cord blood unit with 2 mismatches, 54 (44%) with one mismatch and 5 (4%) received matched units. Conditioning regimen varied according to the disease and the center. Cord blood (CB) units came from CB banks from the USA (n=86), Europe (n=64), and Brazil (n=23). Most patients (94%) received a myeloablative regimen; TBI was used in 86% of cases and ATG/ALG in 82%. Median number of total nucleated cells infused was 4.4×107/kg of recipient weight and the median number of CD34+ cells infused was 1.7×105/kg. Median follow-up time of survivors was 30 months. The cumulative incidence (CI) of neutrophil engraftment at day 60 was 61%, after a median time of 22 days (range 12-55 days) and the CI of platelet engraftment at day 60 was 42%, after a median time of 41 days (range 16-125 days). CI of neutrophil engraftment was only 39% for patients with CML. Nucleated or CD34+ cell dose, number of HLA disparities, bank origin or other patient, disease or transplant-related factors were not associated with engraftment. Techniques of CB thawing, CB unit transportation or cell viability were not analyzed. Only experience of centers (more than 30 UCBT performed) was associated with improved engraftment rate (p=0.05). CI of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 19% and of chronic GVHD only 5% at 3 years. CI of non-relapse related mortality (NRM) was 41%. In a multivariate analysis, factors significantly associated with a higher NRM were patients older than the median age (51% vs. 32% for younger patients, p=0.05), and CD34+ cell dose lower than 1×105/kg (54% vs. 25% P=0.002). At 3 years, the CI of relapse or progression was 20%, and the estimated progression-free survival (PFS) was 36%. In a multivariate analysis, the most important factors associated with a decreased PFS rate were advanced disease status (28% vs. 46% for patients in remission, p=0.001), and a CD34+ cell dose lower than 1×105/kg (21% vs. 42%, p=0.04). At 3 years, estimated overall survival was 41%. In conclusion, UCBT in Brazil seems to be associated with lower engraftment rates as compared to the published experience from other countries. Other factors such as CB unit transportation, CB thawing and cell viability may be analyzed in order to explain the lower engraftment rates. Nevertheless, use of HLA-mismatched UCBT is a valuable alternative for patients with hematologic malignancies in Brazil who lack an HLA-matched related or unrelated donor. UCB units with a higher CD34+ cell count and transplants performed for patients in remission may improve outcomes. Disclosures: No relevant conflicts of interest to declare.

Description: The current experience in the use of multiparametric flow-cytometry for immunological detection of MRD in AML, indicates that the method is feasible, rapid and relatively sensitive. In our previous studies of AML patients with aberrant phenotype (Blood 2000, Leukemia 2003 & 2006), we found that the level of MRD after consolidation therapy was the best predictor of outcome. In fact, a MRD level higher than 3.5x10−4 residual leukemic cells after consolidation was significantly correlated with a poor outcome. The major problem with using an empirically established cut-off to define thresholds is that it may not be reproducible over different populations of patients. In order to confirm the prognostic value of the threshold of 3.5x10−4 residual leukemic cells, previously selected, we used the Maximally Selected Rank Statistic analysis to determine optimal cutpoint, yielding the best separation of AML patients into two groups with different OS and/or RFS probabilities. To do this, we evaluated the trend of standardized log-rank statistics using RFS (Fig. 1, upper panels) and OS (Fig. 1, lower panels) as dependent variables, and the values of residual leukemic cells, determined both at the post-Induction (post-Ind) and post-consolidation (post-Cons) checkpoints, as independent variable (Fig. 1A and 1B, respectively). The experimental cut-off points, identified as the absolute peak in standardized log-rank statistics plots (vertical dotted lines in Fig. 1), were 3.7x10−4 and 3.4x10−4 residual leukemic cells for post-Ind and post-Cons values, respectively. According to this data we decided to utilize the 3.5x10−4 residual leukemic cells cut-off value to discriminate MRD− from MRD+ cases both after induction and consolidation. Therefore, patients with a residual leukemic cells values below the cutoff of 3.5×10−4 will be referred to as MRD−, while those with residual leukemic cells equal or exceeding the 3.5×10−4 level will be classified as MRD+. Post-Cons MRD− patients had a superior outcome in terms of relapse rate (27% vs. 78%, P

Description: Although bone marrow (BM) and peripheral blood mobilized hematopoietic stem cells (PBSC) are widely used as graft sources in patients undergoing hematopoietic stem cell transplantation (HSCT), the graft of choice for each subset of patients remains to be determined. Several studies have, prospectively and retrospectively, addressed this question with inconsistent results. While the increased incidence of chronic graft versus host disease (cGVHD) in PBSC recipients has been unanimously found, data regarding disease free survival (DFS), overall survival (OS) and acute graft versus host disease (aGVHD) incidence have been controversial, mainly for patients with high risk disease. We retrospectively compared the clinical outcomes of 334 patients with acute leukemia and chronic myeloid malignancies receiving related BMT or PBSCT after myeloablative conditioning regimen, treated at seven transplantation centers in Brazil from 2008 to 2009. Median OS was 2.85 and 2.39 years (HR 1.19; 95% CI, 0.84 to 1.68, p=0.34), and DFS was 2.48 and 2.18 years for BM and PBSC recipients respectively (HR 1.07; 95% CI, 0.77 to 1.48, p=0.70). For patients with high risk disease, median OS was 2.1 and 1.72 years (HR 1.18; 95% CI, 0.73 to 1.91, p=0.50) and DFS was 0.46 and 0.58 years (HR 1.04; 95% CI, 0.66 to 1.64, p=0.86) for BMT and PBSCT respectively. Additionally, in agreement with previous reports, the cumulative incidence of chronic GVHD at three years was 53.7% and 79.8% (HR 1.93; 95% CI 1.38 to 2.69, p〈 0.001) for BM and PBSC respectively (Figure 1). On the other hand, aGVHD incidence / severity, cumulative incidence of relapse and non relapse mortality (NRM) were not different between BM or PBSC recipients. The same being true when only patients with high risk disease were evaluated. Figure 1 Major outcomes after transplant according to bone marrow (dark line) and peripheral blood (gray line) as the graft sources. Overall survival for the whole cohort (panel A), high risk (panel B), cumulative incidences of: and standard risk (panel C) patients; disease free survival for the whole cohort (panel D), high risk (panel E) and standard risk (panel F) patients, and relapse (panel G), grades III-IV aGVHD (panel H) and cGVHD (panel I) for the whole cohort. The only outcome that was statistically different was the cumulative incidence of cGVHD – (item I) Figure 1. Major outcomes after transplant according to bone marrow (dark line) and peripheral blood (gray line) as the graft sources. Overall survival for the whole cohort (panel A), high risk (panel B), cumulative incidences of: and standard risk (panel C) patients; disease free survival for the whole cohort (panel D), high risk (panel E) and standard risk (panel F) patients, and relapse (panel G), grades III-IV aGVHD (panel H) and cGVHD (panel I) for the whole cohort. The only outcome that was statistically different was the cumulative incidence of cGVHD – (item I) In conclusion, in our cohort, there was no OS or DFS benefit for patients receiving PBSC when compared to BM recipients, even when only high risk patients were analyzed. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction. Elderly patients with chronic lymphocytic leukemia (CLL) are often treated with chemoimmunotherapeutic regimens. Because of ineligibility for Fludarabine-based protocol, Bendamustine plus Rituximab (B-R) or Chlorambucil plus Rituximab (Chl-R) are the common preferred schemes, chosen in fit or unfit elderly patients, which can obtain good response and less toxicity. In literature overall response rates (ORR) between 66% to 84% and complete responses (CR)ranging from 8% to 26% have been reported Chl-R; for B-R, the ORR ranged between 88% and 98% with CRbetween 25% to 38%. Aim and methods. We compared these two regimens in a multicentre group to understand why and how physicians could choose among these schemes and to establish the advantages and disadvantages of each one in terms of safety and efficacy. To this end, we performed a subgroup analysis: high-risk group (HR) included patients with 17p or 11q and/or unmutated IGHV, standard-risk group (SR) patients without 11q or 17p but with mutated IGHV. We conducted a retrospective analysis on the experience, in clinical practice, of B-R and Chl-R as frontline treatment for elderly (≥65 years) CLL patients treated at 8 haematological centres in the Lazio region. Results. One hundred and ninety-two patients who underwent treatment between 2009 and 2016 were enrolled into the study: 111 patients with B-R and 81 with Chl-R. Patients' characteristics are summarized in Table 1. The median number of B-R cycles was 6 (range 1-6); B dose was 90 mg/m2 (administered at baseline 70 mg/m2 in 19 patients, 17%). The median number of Chl cycles was 6 (range 3-10) and of R was 6 (range 1-8). The two main schedules used for Chl were 1 mg/kg for each cycle every 28 days, given at a fixed daily dose of 10 mg starting from day 1 and repeated for 8 cycles, and 8 mg/m2/day for seven days of each of eight 28-day-cycles. R was administered in both the 2 schemes on day 1 of each cycle at a dose of 375 mg/m2 during the first administration and 500 mg/m2 for the subsequent cycles. On an intention to treat basis, the ORR was 93.6% in B-R (54.9% complete response, CR, and 38.7% partial response, PR) and 86.5% in Chl-R (30.9% CR and 55.6% PR). In B-R group 45 patients (40.5%) progressed with a median progression-free survival (PFS) of 46 months (CI 95%, 40-59), 38 (34.2%) required re-treatment with a median time to retreatment (TTR) of 53 months (CI 95%, 43-63), 10 (9.0%) died but median overall survival (OS) was not reached; we registered 47.8% of haematological toxicity (36.0% grade III-IV) and 46% of extra-haematological toxicity (13.5% grade III-IV); the most frequent serious adverse events were neutropenia and cutaneous reactions, respectively. Thirty-eight (34.2%) patients had to reduce B dose, 13 (11.7%) were hospitalized. In Chl-R group 45 patients (55.6%) progressed with a median PFS of 37 months (CI 95%, 30-39), 39 (48.2%) required re-treatment with a median TTR of 46 months (CI 95%, 36-58), 18 (22.2%) died with a median OS greater than 100 months; we registered 28.4% of haematological toxicity (22.2% grade III-IV) and 27.2% of extra-haematological toxicity (11.1% grade III-IV); the most frequent serious adverse events were neutropenia, R infusion reactions and respiratory events, respectively. Fifteen (18.5%) patients had to reduce Chl dose, 7 (8.6%) were hospitalized. We found a statistical difference among the schemes in terms of ORR (better response in B-R, p=0.002, but it was not significant when analysed considering B cycles, 6 cycles vs less than 6 cycles, and dose reduction) and in terms of haematological and extra-haematological toxicity (more toxicities in B-R than Chl-R, p=0.007 and p=0.010 respectively, but it was not different if considered the type and the grade). When comparing Kaplan-Meier curves of PFS, TTR and OS we did not find any statistical difference. Subgroup analysis of the HR and SR showed that no differences were found in the outcome curves for both PFS, TTR and OS in B-R group and Chl-R group. Conclusions. ORR are very good in both groups, confirming the role of Chl and of B in association with R in elderly patients. The high rate of ORR in comparison with other published study was also due to the main dose of B and Chl used. Our study focused on elderly (≥65 years) untreated CLL patients, in whom B-R regimen is associated with better response but also higher toxicity in comparison to Chl-R. In the real life, the physician seems to apply the Chl-R protocol to very elderly or unfit CLL patients. Disclosures Del Principe: Gilead: Membership on an entity's Board of Directors or advisory committees. Mauro:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Introduction Limited stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), although different approaches are currently carried out, ranging from watch and wait to combined treatment. RT on involved lymph nodes allows eradication of the disease only in 40-50% of patients. Anti-CD20 monoclonal antibodies (MoAb), widely used in advanced stage FL, are likely to be effective in reducing the relapse risk, although no scientific evidence of their role has been provided. The aim of this multicenter phase II prospective study was to evaluate the role of MRD in identifying patients unlikely to be cured by RT, for whom an immunotherapy-based consolidation could improve outcome. Methods 110 patients with stage I/II FL were enrolled. IFRT was administered to all patients at a dose of 24 Gy. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the Italian FIL (Federazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories: the presence of a BCL2/IGH rearrangement was investigated at baseline in all patients by nested PCR (NEST) and RQ-PCR (RQ), the latter according to the EuroMRD guidelines. In patients BCL2/IGH+ at baseline by both NEST and RQ in BM and/or PB, MRD was analyzed in both tissues after IFRT and every 6 months over a three-year follow-up period. Patients with positive MRD by both NEST and RQ in BM and/or PB after IFRT or who became positive during the follow-up were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab. The primary objective of the study was to define the efficacy of immunotherapy in obtaining the disappearance of BCL2/IGH rearranged cells. Results Preliminary data are available for 107 patients, 57 males, 50 females. Median age was 55 years (29-83). 17% had G1 FL, 32% G2, 40% G3A, 11% NOS. The FLIPI score was 0 in 59% of patients, 1 in 35%, 2 in 6%. 69% of patients had inguinal site involvement. Despite a negative BM biopsy, at baseline 30% of patients (n=32) had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in the BM and/or PB; the concordance between compartments was 90%, with 10% of negative PB showing a positive BM. No significant differences were observed in relapse probability between patients with or without a molecular marker. All patients were submitted to IFRT and all obtained a clinical response, which was complete in 79 of the 101 evaluated patients (78%) and partial in 22 (22%). MRD evaluation after treatment revealed the persistence of BCL2/IGH rearranged cells in the PB and/or BM in 60% of patients. According to the design of the protocol, MRD-positive patients, either after IFRT (n=18) or in case of conversion to a positive signal during the follow-up (n=7), received 8 weekly administration of ofatumumab. A conversion to MRD negativity, evaluated in 23 treated patients, was obtained in 20 (87% - CI 65.1-97.1). This result was significantly superior to the expected 50%. One death occurred after IFRT, due to ischemic stroke. Adverse events likely correlated to ofatumumab occurred in 7/25 treated patients, consisting of infusion reactions in 5, leading to a permanent interruption of immunotherapy in 3. After a median follow-up of 18 months, all patients who achieved a MRD negativity with ofatumumab underwent a regular molecular follow-up and are still MRD-negative. Overall, clinical relapse or progression were observed in 17 patients: 13 (18%) among the 73 "no marker" patients; 2 relapses (16%) were observed among the 12 MRD-negative patients after IFRT and 2 relapses were observed among the 23 patients treated with the anti-CD20 MoAb (8.7%), 1 having achieved a MRD negativity and 1 not. No significant differences in event-free survival have so far been observed between the three groups. Conclusions The MRD data of this phase II trial for early stage FL indicate that RT alone is often insufficient to eradicate the disease, being capable of inducing a negative MRD only in 40% of evaluable cases, with a long-lasting effect only in half of them. The primary objective of this study - MRD negativity after immunotherapy - was achieved, obtaining the disappearance of BCL2/IGH rearranged cells in the majority of patients treated with ofatumumab. The strategy of an immunotherapy consolidation after IFRT in MRD-positive patients allowed to increase molecular responses. A longer follow-up and further studies on larger patient populations will allow to conclusively define the impact of this MRD-driven strategy also on clinical outcome. Disclosures Pulsoni: Roche: Consultancy, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy; Sandoz: Consultancy; Gilead: Speakers Bureau; Merk: Consultancy; Bristol Meyer Squibb: Speakers Bureau. Ferrero:Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Liberati:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Celgene: Honoraria, Other: Clinical trial support; Bristol-Myers Squibb: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Roche: Other: Clinical trial support; Novartis: Other: Clinical trial support. Ferreri:Roche: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Kite: Consultancy. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Corradini:Roche: Honoraria; Novartis: Honoraria; kite: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria. Mannina:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Arcaini:Celgene: Speakers Bureau; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses. Galimberti:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Ladetto:AbbVie: Honoraria; Roche: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; J&J: Honoraria; Celgene: Honoraria. Foà:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: The anti-CD20 MoAb Ofatumomab is employed to eradicate Minimal Residual Disease in early stage Follicular Lymphoma(FL). The drug is registered for Chronic Lymphocytic Leukemia, not for FL.