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Chronic lymphocytic leukemia (CLL) is characterized by significant biologic and clinical heterogeneity. This study was designed to explore CLL B-cells’ proteomic profile in order to identify biologic processes affected at an early stage and during disease evolution as stable or progressive. Purified B cells from 11 untreated CLL patients were tested at two time points by liquid chromatography–tandem mass spectrometry. Patients included in the study evolved to either progressive (n = 6) or stable disease (n = 5). First, at an early stage of the disease (Binet stage A), based on the relative abundance levels of 389 differentially expressed proteins (DEPs), samples were separated into stable and progressive clusters with the main differentiating factor being the RNA splicing pathway. Next, in order to test how the DEPs affect RNA splicing, a RNA-Seq study was conducted showing 4217 differentially spliced genes between the two clusters. Distinct longitudinal evolutions were observed with predominantly proteomic modifications in the stable CLL group and spliced genes in the progressive CLL group. Splicing events were shown to be six times more frequent in the progressive CLL group. The main aberrant biologic processes controlled by DEPs and spliced genes in the progressive group were cytoskeletal organization, Wnt/β-catenin signaling, and mitochondrial and inositol phosphate metabolism with a downstream impact on CLL B-cell survival and migration. This study suggests that proteomic profiles at the early stage of CLL can discriminate progressive from stable disease and that RNA splicing dysregulation underlies CLL evolution, which opens new perspectives in terms of biomarkers and therapy.

Currently, prognostic models in diffuse large B-cell lymphoma (DLBCL) fail to closely reflect patients' biological, clinical, and survival heterogeneity. We, therefore, assessed the impact of clinical, biological, immunohistochemical (IHC), baseline (0), and interim (after 2 and 4 treatment cycles) PET (PET0, PET2, and PET4) data not yet included in any scoring system on DLBCL outcome. The analysis was conducted on 89 previously untreated adult patients of the Finistere Observatory Cohort (O.Ly.Fin) with documented DLBCL, recruited between January 2010 and December 2017, with progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints, respectively. Seventy-eight patients were treated with rituximab, cyclophosphamide, hydroxyadriamycin, vincristine, and prednisone (R-CHOP), while 11 received R-dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and hydroxyadriamycin (EPOCH). Patients were followed up until June 20, 2020. On multivariate analysis, Ki67 ≥ 70% on IHC (K), bulky presentation ≥7.5 cm (B), meningeal lymphomatosis (M), and PET0–PET4 ΔSUVmax de novo DLBCL patients.

Richter syndrome (RS) is an aggressive lymphoma arising on the back of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and is the most common B-cell malignancy in the Western world. In the majority of cases, RS presents an activated B cell (ABC) phenotype of diffuse large B-cell lymphoma (DLBCL). From the therapeutic point of view, selective inhibition of PI3Kδ with idelalisib represents a valuable addition to available treatment options for patients with CLL/SLL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. However, to our knowledge, there have been no prospective studies evaluating idelalisib efficacy in a DLBCL-ABC form of RS. Here, we present a case of a DLBCL-ABC form of RS achieving a complete response at 3 weeks after initiating idelalisib and rituximab therapy for six cycles. This response was maintained during the idelalisib monotherapy, but the patient relapsed rapidly after treatment was withdrawn, because of a grade three immune colitis that developed at 10 months of treatment. This report demonstrates that idelalisib is highly effective in RS and provides an attractive option in this aggressive disease. This agent could meet an unmet need by providing a treatment option with a tolerable safety profile for elderly patients with RS.

The solar energy is the most available, non-polluting and free source of energy. Solar photovoltaic energy is the fastest growing energy resource and it will someday become the dominant source of energy. Iraq is located 290N-370N latitude so, it has a good possibility of solar energy, which could be invested to generate the electrical power by the photovoltaic modules. The used databases in this study are hourly data of irradiance were obtained from Photovoltaic Geographical Information System (PVGIS) while air temperature and wind speed were obtained from the European Centre for Medium-Range Weather (ECMWF) for the period 1/1/2001-31/12/2012. Mathematical MATLAB program has been created to estimate the cell temperature and electrical power of a monocrystalline module for 200 sites in Iraqi areas. This study states the effects of environmental parameters on both the cell temperature and the electrical power of a monocrystalline PV module. Irradiance on tilt surface, ambient temperature, and wind speed are the key environmental factors in this study. By using Arc GIS, maps of electrical power and cell temperature distributions of a monocrystalline were drawn based on NOCT model.It has found that the effect of solar radiation on the output electrical power from the PV module is greater than the effect of ambient air temperature. Also, it has found that the monthly electrical power received from the module is varied throughout the months for the study area where the highest electrical power was recorded in June and the lowest electrical power recorded in December. Also, it varies in different sites, the southern part of Al- Qadisyah, western part of Dhi-Qar, northern part of Al-Muthannia and southwestern part of Al-Anbar provinces recorded the highest values of electrical power while the lowest value in the eastern part of Dihok.

The general administration of pharmaceutical care started potential pharmacy practice program. The program is part of accreditation professional’s process of national and international regulations. The adult’s parenteral nutrition was one of the critical programs. The most healthcare professionals are not familiar with the new system. The new initiatives system adult’s standardized concentration formulation of total parental nutrition as complementary to the previous one. The new formulation consisted of all parental nutrition requirements based on national and international standards. The new system can be converted as computerized physician orders. The new initiatives may implement as project management model over one year or less than that’s. The new system prevents nutrition-related problems, and medication errors, and improve clinical outcomes of the adults’ population in the Kingdom of Saudi Arabia.

The national total parental nutrition program with an emphasis on pediatrics started before several ago at Ministry of health hospitals In Kingdom of Saudi Arabia. The program covered several regions and consisted from the foundation of Intravenous Admixture and preparation of pediatric parenteral nutrition to administration and follow up of patients outcomes. In addition to the prior system, the new initiative project with the standardized formulation of pediatric’s parenteral nutrition is the complementary project of the parental nutrition for pediatrics. The project initiated to prevent drug-related problems of parental nutrition, improve patient clinical outcome and reduce the unnecessary economic burden on the healthcare system. It is the new system in the Middle East and Gulf counties in additional to Saudi Arabia. The initiatives are the systemic implementation of standardized pediatrics formulation using management project tools of starting new idea until finding in the ground.

The total parental nutrition considered as high alert medications for neonates population and others. Several medications safety institutions and international with national accreditation organization recommended setting prevention measure of medical error events. The new medications safety project initiative was neonates standardized parental nutrition formulation. The formulation contained all requirements of American Parenteral and Enteral Nutrition and European Parental and Enteral Nutrition standard. Also, to the United State Pharmacopeia 797 stranded. The formulation is suitable for neonates with formal renal and hepatic functions with common neonate’s requirements Parenteral Nutrition in Saudi Arabia. The new initiative’s project may implement through explored project management tools with close measurements of performance indicators outcome. The neonate’s standardized formulation of parental nutrition new programs at Ministry of Health hospitals in the Kingdom of Saudi Arabia with Gulf and Middle East counties.

Background: Pharmacy practice residency program (PPRG) is one of a major professional degree in Saudi Arabia. The residency is very high demand in the pharmacy market. The clinical pharmacist required to visit hospitals to improve the services and start the program. Objective: The goal of this study to explore the value of clinical pharmacist consultation visit with emphasis on clinical pharmacy services (CPS) and pharmacy education and training (PET) at Ministry of Health hospitals in Riyadh, Saudi Arabia. Methods: It is a twelve months cohort study of a regular visit to three major hospitals included public, pediatrics with maternity and emergency specialties at Riyadh region. The assessment used based on Saudi hospital pharmacy standards, MOH pharmacy strategic plan, and the 6-points Likert assessment scale system before the study and by the end of the study. The total number of finished projects were eighteen projects divided between CPS (twelve projects) and PET (six projects). Results: The improvements range changes in CPS from 16.7% to 100% with average positive improvement 48%. In the PET the improvements range changes were 32.8% to 100% with average positive changes was 85%. The highest score of the projects of CPS was an assessment of pharmacy services, assessment of emergency pharmacy services, and assessment of critical pharmacy services. The maximum score of the projects of PET was doing an interview with hiring a new pharmacist, train drug Information for staff pharmacist, and apply on the job training for the new pharmacist. Conclusion: The pharmacist showed practical significance impact on the clinical pharmacy services and pharmacy education and training in Riyadh city, Saudi Arabia. The increasing number of consultation visit with regular evaluation is necessary to keep continues pharmacy improvement at all hospital pharmacies. Key words: Impact, Clinical Pharmacist, Hospital Pharmacy, Ministry of Health, Saudi Arabia.

Chronic lymphocytic leukemia (CLL) is associated with abnormal T-cell responses responsible for defective anti-tumor activities. Intriguingly, CLL B cells share phenotypical characteristics with regulatory B (Breg) cells suggesting that they might negatively control the T-cell activation and immune responses. We elaborated an in vitro co-culture system with T cells to evaluate the Breg capacities of CLL B cells following innate Toll-like receptor 9 (TLR9) engagement. We demonstrated that B cells from half of the patients exhibited regulatory capacities, whilst B cells from the remaining patients were unable to develop a Breg function. The T cell sensitivities of all patients were normal suggesting that defective Breg activities were due to intrinsic CLL B cell deficiencies. Thus, TLR-dedicated gene assays highlighted differential signature of the TLR9 negative regulation pathway between the two groups of patients. Furthermore, correlations of the doubling time of lymphocytosis, the time to first treatment, the mutational status of IgVH and the Breg functions indicate that patients with efficient Breg activities have more aggressive CLL than patients with defective Breg cells. Our in vitro observations may open new approaches for adjusting therapeutic strategies targeting the Breg along with the evolution of the disease.

Background Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]). The two 5-cytosine derivatives, 5-methylcytosine (5-mCyt) and 5-hydroxymethylcytosine (5-hmCyt), were tested by ELISA (n = 60), while real-time quantitative PCR was used for determining transcriptional expression levels of DNMT and TET (n = 24). Results By using global DNA methylation/demethylation levels, in the low-risk disease group, two subgroups with significantly different clinical outcomes have been identified (median treatment-free survival [TFS] 45 versus > 120 months for 5-mCyt, p = 0.0008, and 63 versus > 120 months for 5-hmCyt, p = 0.04). A defective 5-mCyt status was further associated with a higher percentage of 13q deleted nuclei (> 80%), thus suggesting an acquired process. When considering the cytogenetic intermediate/high-risk disease groups, an association of 5-mCyt status with lymphocytosis (p = 0.0008) and the lymphocyte doubling time (p = 0.04) but not with TFS was observed, as well as a reduction of DNMT3A, TET1, and TET2 transcripts. Conclusions Combining cytogenetic studies with 5-mCyt assessment adds accuracy to CLL patients’ prognoses and particularly for those with 13q deletion as a sole cytogenetic abnormality.

// Cristina Bagacean 1, 2, 3 , Adrian Tempescul 1, 4 , Christelle Le Dantec 1 , Anne Bordron 1 , Audrey Mohr 1 , Hussam Saad 4 , Valerie Olivier 2 , Mihnea Zdrenghea 3, 5 , Victor Cristea 3 , Pierre-Francois Cartron 6 , Nathalie Douet-Guilbert 7 , Christian Berthou 1, 4 and Yves Renaudineau 1, 2 1 U1227 B Lymphocytes and Autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, Networks IC-CGO and REpiCGO from Canceropole Grand Ouest, Brest, France 2 Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, France 3 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania 4 Department of Hematology, Brest University Medical School Hospital, Brest, France 5 Department of Hematology, ‘Ion Chiricuta’ Oncology Institute, Cluj-Napoca, Romania 6 Inserm, U892, Epigenetics Network from Canceropole Grand Ouest, Nantes, France 7 Laboratory of Cytogenetics, Brest University Medical School Hospital, Brest, France Correspondence to: Yves Renaudineau, email: yves.renaudineau@univ-brest.fr Keywords: chronic lymphocytic leukemia, methylation, hydroxymethylation, TET, SAT1 Received: June 08, 2017 Accepted: July 26, 2017 Published: August 09, 2017 ABSTRACT Cytosine derivative dysregulations represent important epigenetic modifications whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5-hydroxymethyluracil were tested in purified B cells from CLL patients ( n = 55) and controls ( n = 17). The DNA methylation ‘writers’ (DNA methyltransferases [ DNMT1/3A/3B ]), ‘readers’ (methyl-CpG-binding domain [ MBD2/4 ]), ‘editors’ (ten-eleven translocation [ TET1/2/3 ]) and ‘modulators’ ( SAT1 ) were also evaluated. Accordingly, patients were stratified into three subgroups. First, a subgroup with a global deficit in cytosine derivatives characterized by hyperlymphocytosis, reduced median progression free survival (PFS = 52 months) and shorter treatment free survival (TFS = 112 months) was identified. In this subgroup, major epigenetic modifications were highlighted including a reduction of 5-mCyt, 5-hmCyt, 5-CaCyt associated with DNMT3A , MBD2/4 and TET1/2 downregulation. Second, the cytosine derivative analysis revealed a subgroup with a partial deficit (PFS = 84, TFS = 120 months), mainly affecting DNA demethylation (5-hmCyt reduction, SAT1 induction). Third, a subgroup epigenetically similar to controls was identified (PFS and TFS > 120 months). The prognostic impact of stratifying CLL patients within three epigenetic subgroups was confirmed in a validation cohort. In conclusion, our results suggest that dysregulations of cytosine derivative regulators represent major events acquired during CLL progression and are independent from IGHV mutational status.

La traduction des ARNm est une etape regulatrice importante de l'expression des genes au cours de differents mecanismes physiologiques et physiopathologiques, incluant la proliferation cellulaire et l'apoptose. Parmi les maladies du cycle cellulaire, la leucemie lymphoide chronique B-CD5 + (LLC) est caracterisee par une perte de l'apoptose. Les proteines eIF4E (eukaryotic Initiation Factor 4E) et 4E-BPs (eIF4E Binding Proteins), qui jouent un role important dans la regulation traductionnelle, ont recemment ete impliquees dans les mecanismes de survie et d'apoptose. Nos etudes ciblant ces acteurs au cours du developpement embryonnaire precoce de l'oursin nous ont permis de souligner leur importance pour l'entree dans le cycle cellulaire en reponse a la fecondation. Dans ce modele, la degradation de 4E-BP represente un nouveau mecanisme de controle de la traduction et doit etre pris en compte dans d'autres mecanismes physiologiques et physiopathologiques. L'ensemble des donnees permet de proposer les facteurs eIF4 comme cible potentielle pour de nouvelles approches therapeutiques contre le cancer en general et contre la LLC en particulier. Cette revue met en evidence l'apport du modele biologique du developpement precoce de l'oursin dans cet axe de recherche qui associe de facon originale une equipe de recherche de biologie cellulaire et une equipe medicale specialisee dans la cancerologie de la leucemie lymphoide chronique B-CD5 + .

BACKGROUND Acute leukemia (AL) requiring cytotoxic treatment occurring during pregnancy poses a very difficult therapeutic dilemma. METHODS By means of a mail questionnaire, information on a series of 37 patients with a diagnosis of AL during pregnancy was collected from 13 French centers between December, 1988 and November, 2003. RESULTS Thirty-one patients had acute myeloid leukemia (AML), and 6 patients had acute lymphoblastic leukemia (ALL). Nine patients were diagnosed during the first trimester, 10 patients were diagnosed during the second trimester, and 18 patients were diagnosed during the third trimester. Fifteen pregnancies ended with therapeutic or spontaneous abortion. There were 13 normal deliveries, including 1 gemellary pregnancy, and 9 Cesarean sections. Twenty-three healthy babies survived from the 37 pregnancies, of whom 15 babies had been exposed to chemotherapeutic agents. A complete remission was achieved in 34 patients. Eleven women had severe extrahematologic complications during the induction remission course. The median disease-free survival (DFS) was not reached, with a 5-year DFS of 54%. Ten patients developed recurrent disease. Overall, 12 of 37 pregnant women died from leukemia. CONCLUSIONS Pregnancy does not affect the course of AL. In the first trimester, termination of pregnancy should be discussed because of the potential fetal consequences of chemotherapy. Chemotherapy treatment during the second or third trimester may not require termination of pregnancy, because as remission of AL and delivery of a normal infant are likely to be obtained. Cancer 2005. © 2005 American Cancer Society.

Introduction: For relapsed or refractory (R/R) CLL patients (pts), combination of bendamustine and rituximab appears safe and effective (Fischer 2011). Ofatumumab monotherapy gives 58% ORR in heavily pre-treated (median 4 prior lines) R/R CLL pts (Wierda JCO 2010). High doses (HD) steroids are also active in poor prognosis pts with bulky nodal involvement or p53 impairment (Castro 2008, Xu 2010). We report a planned interim analysis of the ICLL01-BOMP phase II trial evaluating the association of Bendamustine, Ofatumumab and high-dose MethylPrednisolone for fit R/R CLL pts after 1-3 previous lines (NCT01612988). Patients and Methods: Primary endpoint was CR rate after 6 cycles (cy) of the BOMP regimen [i.e. bendamustine (70 mg/m2 d1, d2), ofatumumab (1000 mg d1;15 on cy#1-2 and d1 on cy#3-6) and HD methylprednisolone (1 g/m2 d1-3)]. The c#1 was preceded by an ofatumumab (300 mg) prephase. Response evaluation (IWCLL 2008) was done 3 months (m) after the last cy along with blood and bone marrow 10-color flow MRD analysis. Results: Among the 55 pts of this analysis, median age was 64 years (44-76). CIRS-G comorbidity score was 2-6 in 61% and pts had received 2-3 lines in 37% of the cases. Prior FCR-like regimens (50 (91%) patients) had been followed by relapse within 2y in 22/55 and 5/55 pts were fludarabine-refractory (FR). IGVH was unmutated (UM) in (47/52) 90.4%. Karyotypes were complex in 18/46 (39%) cases. Distribution according to FISH hierarchical model was: del(17p) in 15 (27%), del(11q) in 14 (26%), trisomy 12 in 4 (7%), del(13q) in 17 (31%) and normal in 5 (9%). Mutations on the TP53, SF3B1 and NOTCH1 genes occurred in 17 (31%), 14 (26%) and 5 (9%) pts, respectively. According to published risk stratification (Zenz, 2012), 34/55 pts (62%) belonged to the “highest-risk” group with either TP53 disruption (deletion and/or mutation) (n=19) and/or early relapse within 2 years post-FCR (n=22). The remaining patients belonged to either the “high-risk” group (UM-IGVH and/or Highb2mic and/or del11q) accounting for 17 pts (31%) or to the “low-risk” group (or non evaluable) accounting for 4 (7%) pts. Overall, 292 BOMP cy (mean 5.3 cy/pts) were delivered. Safety analysis recorded 158 grade 3-4 adverse events (G3-4/AE) with according to cy: neutropenia: 20.8%, thrombocytopenia: 11.3%, anemia: 2.4%, infection: 5,8%, hyperglycemia: 7,5%, liver enzyme elevation: 1,4%, cutaneous reaction: 1,4%, ofatumumab infusion related reaction: 0,3% and other AE: 3,4%. Overall 43 out of 55 pts (78.2%) had at least one G3-4/AE. Twenty-eight severe adverse events were reported in 20 pts. Treatment interruption before planned 6 cy occurred for pts' decision (n=3), excessive toxicity (n=5) or early progressive disease (PD) (n = 4). Response in the ITT population was 76.4% ORR with 20% CR (n=11), 56.4% PR (n=31 including 5 nPR and 1 CRi), 9.1% stable disease (n=5), 10.9% PD (n=6) and 3.6% (n=3) non evaluable. Blood MRD obtained in 45 pts was negative ( With median follow-up of 16.2 (5.1-23.6) months (m) we observed 9 deaths, related to PD (n=5), EBV-induced lymphoproliferation (n=1), PML encephalitis (n=1), sepsis/pancytopenia (n=1) or unknown origin (n=1). We recorded 22 relapses (including 4 Richter Syndromes) resulting in treatment in 17 cases, with a BTK inhibitor in 8 cases. The median OS has not been reached (estimation 84% at 18 m) (Fig 1B). The median PFS was 18.4 m (95%CI, 14.6-22.2) and the median time to next treatment 17.6 m (95%CI, 12.9-22.4). With 5 cases censored at time of RIC-Allo, the PFS (censored analysis) was 17.5 m (95%CI, 13.2-21.8). (Fig 1A) After univariate analysis, ORR was lower in the “highest-risk” (64,6%, p=0.01), del(17p) (40%, p=0.003), TP53 mutation (47.1%, p=0.01) and complex karyotype (61.2%, p=0.024) groups. PFS was shorter in the “highest-risk” (14 m, p=0.046), FR (4.96 m, p Conclusion: Relapse treatment of CLL is a challenge especially after prior FCR-like treatments, accounting for >90% of this trial population. These results in terms of response and survival appear noteworthy considering that >60% are “highest-risk” pts. This study provides important information for forthcoming comparison with next emerging CLL therapies. Figure 1 Figure 1. Disclosures de Guibert: Roche: Honoraria. Feugier:Roche: Honoraria. Schuh:Roche, Gilead, GSK, NAPP, Celgene: Honoraria. Leblond:Roche: Honoraria, Speakers Bureau. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding.

Abstract 3066 Introduction: Advanced stage III/IV or relapsed/refractory follicular lymphoma (FL) can hardly be cured with conventional chemotherapy and patients, even after autologous stem cell transplantation (ASCT), experience innumerable relapse events occurring at decreasing progression-free intervals. Important progress was made since the introduction of RITUXIMAB as part of frontline chemoimmunotherapy or as maintenance after frontline treatment with or without ASCT. But, whatever the policy applied, no plateau is observed regarding overall survival (OS) and progression-free survival (PFS). Disease relapse, even in patients with documented complete remission (CR), is thought to be induced both by resistant minimal residual tumor cells and the lack of immunocompetent mechanisms to contain or eliminate them. Thus, it has been postulated that post-ASCT consolidative immunotherapy might eradicate minimal residual disease, based on antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism, and have a favorable impact on relapse rate and even OS. This view has led to a considerable interest in immunotherapy as a promising therapeutic line to restore and enhance the impaired anti-tumor immune surveillance in the context of post-ASCT low tumor burden. Purpose: We conducted a phase II study to compare OS and PFS between patients with advanced or relapsed/refractory FL receiving consolidative immunotherapy combining recombinant interleukine-2 (rIL-2), recombinant interferon- α-2b (rINF- α-2b) and RITUXIMAB after ASCT, with the aim of controlling minimal residual disease, and other counterparts with FL receiving no further treatment after ASCT. Patients and Methods: From August, 1995, to October, 2009, 139 patients with FL were autografted in complete remission ≥1 or partial remission. Of these patients, 66 were considered eligible for immunotherapy. On adequate post-ASCT hematologic reconstitution, they received 4 weekly IV injections of RITUXIMAB administered on an outpatient fashion. This was followed by a home-based program of subcutaneous injections of rIL2 (6 million UI × 3 / week in 1st cycle; 9 million × 3 / week in 2d) and rINF- α-2b (1.5 million UI × 3 / week in 1st cycle; 3 million × 3 / week in 2d) administered over two 7-week cycles. These two cycles were separated by a two-week free interval. The other 73 patients did not receive any additional treatment after ASCT and served as controls. Results: The two groups were comparable regarding demographic characteristics, disease profile and treatment course, except that the control group had significantly less transformed FL (p =0.0156) and a higher mean treatment line number (p =0.018). Median OS and PFS were not reached in either the study group or the control group. OS, initially not different between the 2 groups (p =0.21), was found significantly higher in the study group after a cut-off follow-up time point of 86.6 months (p =0.017). A significantly higher PFS was also noted in favor of the study group over the control group (p =0.0131). With a median follow-up of 60 months (10 to 136) in the study group and of 82 months (0.7 to 174) in the control group, survival rate was 90.9% and 71.2%, respectively (p= 0.0034) and the overall relapse rate was 19.7% (13 patients) and 41.1% (30 patients), respectively (p= 0.0064). Adverse events were generally mild, consisting essentially of fever and chills with the rIL-2 and rINF- α-2b subcutaneous injections (rapidly controlled with PARACETAMOL), fatigue, grade 2 abnormal liver function tests in one third of patients and grade 2 or 3 cytopenias (anemia or neutropenia) in 40% of patients. Conclusion: These results confirm that post-ASCT immunotherapy with rIL2, rINF- α-2b and RITUXIMAB has a statistically significant impact on OS and PFS. In view of its tolerability, it appears to be quite feasible and safe and might be seen as a promising line of treatment designed for eradicating post-ASCT minimal residual disease and worth being tested within the frame of a randomized trial for validation as an essential step in the treatment algorithm of FL. Disclosures: No relevant conflicts of interest to declare.

Abstract 3558 Introduction: A minority of patients with diffuse large B cell lymphoma (DLBCL) can really be cured and the early or late relapse rate remains a subject of major concern. The occurrence of disease relapse, even in patients with documented complete remission (CR), is thought to be induced both by resistant minimal residual tumor cells and the lack of immunocompetent mechanisms to eradicate them. Thus, it has been postulated that post-autologous stem cell transplantation (ASCT) consolidative immunotherapy might eradicate minimal residual disease and, therefore, reduce relapse rate and even improve overall survival (OS). This view has led to a considerable interest in immunotherapy as a promising therapeutic line to restore and enhance the impaired anti-tumor immune surveillance in the setting of post-ASCT low tumor burden. Purpose: We conducted a phase II study to compare OS, relapse-free survival (RFS), death rate and overall relapse rate between patients with poor-risk DLBCL receiving consolidative immunotherapy combining recombinant interleukine-2 (rIL-2), recombinant interferon-α-2b (rINF-α-2b) and Rituximab after ASCT, with the aim of controlling minimal residual disease, and other patients with poor-risk DLBCL treated with ASCT alone. Patients and Methods: On 180 patients, 27 with DLBCL from Brest, autografted in complete remission (CR) ≥ 1 or partial remission (PR), were considered eligible for the study. They received, on adequate post-ASCT hematologic reconstitution, 4 weekly IV injections of Rituximab administered on an outpatient fashion. This was followed by a home-based program of subcutaneous injections of rIL2 (6 million UI × 3/week in 1st cycle; 9 million × 3/week in 2d) and rINF-α-2b (1.5 million UI × 3/week in 1st cycle; 3 million × 3/week in 2d) administered over two 7-week cycles. These two cycles were separated by a two-week free interval. One hundred and fifty three patients from Brest, Lille and Tours did not receive any additional treatment after ASCT and served as controls. Results: The two groups were comparable, except for age, which was older in the study group (p=0.018) and for pre-ASCT response pattern, which was better in the control group. There was no influence of recruitment center, sex, disease Ann Arbor stage, IPI score, RITUXIMAB administration before ASCT, graft source or ASCT conditioning regimen on the final results. Median OS and RFS were not reached in any group and are still under study. The median follow-up was 54.9 months in the study group and 48.8 months in the control group. In univariate analysis, the prevalence of death rate was 7.4% and 26.2% in the study group and the control group, respectively (OR = 0.23, 95%CI [0.05-0.99], p=0.03), and the overall relapse rate was 11.1% (3 patients) and 22.9% (35 patients), respectively (OR=0.42, 95%CI [0.12-1.48], p=0.17). In multivariate analysis, the risk of death was significantly decreased (OR 0.196; 95%CI [0.046-0.827] p=0.027) and there was a trend toward a decreased relapse rate (OR 0.348; 95%CI [0.104-1.168], p=0.088) in the study group compared to the control group. In addition, older age was independently associated with an increased risk of death (OR=1.053, 95%CI [1.02-1.09], p=0.002). Adverse events were generally mild, consisting essentially of fever and chills with the rIL-2 and rINF-α-2b subcutaneous injections responding well to PARACETAMOL, fatigue, grade 2 abnormal liver function tests in one third of patients, grade 3 neutropenia in 45% of patients and hypothyroidism in one patient. Conclusion: We found that post-ASCT immunotherapy with rIL2, rINF-α-2b and RITUXIMAB has a statistically significant favorable impact on death rate and a positive, although not statistically significant, effect relapse rate. In view of its toxicity profile, it appears to be quite feasible and safe and might be considered as a promising line of treatment designed for post-ASCT minimal residual disease and worth being evaluated within the frame of a prospective randomized trial. Disclosures: No relevant conflicts of interest to declare.