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Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when highly emetogenic antineoplastic drugs are used. Uncontrolled emesis can profoundly impact on the patient's quality of life and ability to survive, by causing dehydration, electrolyte imbalance, malnutrition and treatment discontinuation. The ABVD regimen (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) is considered the standard of care for first-line treatment of Hodgkin's Lymphoma. Among these drugs, dacarbazine and adriamycin are the most emetogenic, being classified as highly and moderately emetogenic chemotherapy, respectively. NEPA is the first fixed antiemetic combination composed by the pharmacologically and clinically distinct 5HT3 receptor antagonist (5HT3-RA) palonosetron and the highly selective Neurokinin1/Substance P receptor antagonist (NK1-RA). A single dose of NEPA per chemotherapy cycle acts on the principal pathways involved in the mechanisms controlling nausea and vomiting in a synergistic way with an appropriate half-life to cover both the acute (0-24 hours from chemotherapy) and delayed (25-120 hours) phase. In this open label multicenter study, chemo-naïve Hodgkin's Lymphoma patients who were addressed to receive their first cycle of ABVD regimen (2 doses in 28 days, on days 1 and 15) were given a single administration of NEPA plus 4 mg dexamethasone. The primary endpoint was complete response (CR), defined as no emesis and no rescue medication during the overall phase (0-120 hours) on the first dose of the first ABVD cycle. A total of 77 patients were evaluated. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. Indeed, the number of the complete responders for the overall phase among the first 70 consecutive patients was 66, which is greater than the pre-determined cut-off of 46, representing the minimum frequency of responders for which the treatment is considered effective. In addition to the primary efficacy endpoint, several additional endpoints were evaluated. The CR values were 93.5% for the acute phase, 81.8% for the delayed phase and 80.5% for the overall phase, while Complete Control (CR with no more than mild nausea) were achieved in the 93.5%of patients in the acute phase, 76.6% in the delayed phase and 75.3% in the overall phase (Figure 1A). Also, levels of no significant nausea (no more than mild nausea) were 94.6% for the acute phase, 83.1% for the delayed phase and 81.8% for the overall phase (Figure 1B). This study demonstrated the efficacy of NEPA plus dexamethasone in preventing the nausea and vomiting induced by the highly emetogenic ABVD regimen. Disclosures Abruzzese: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Di Renzo:BerGenBio ASA: Research Funding. Flenghi:takeda: Consultancy; Roche: Consultancy; janssen-cilag: Consultancy; teva: Consultancy; Servier Italia: Consultancy. Cantonetti:Vifor: Consultancy; Mundipharma: Consultancy; Roche: Consultancy; Takeda: Consultancy.

Introduction Erythrocytosis is characterized by persistently raised hemoglobin (HB) and hematocrit (Ht) levels. Differential diagnosis includes Polycythemia Vera (PV), secondary, hereditary (HE) and idiopathic erythrocytosis (IE). Recently, Randi et al. (Br J Haematol, 2018) demonstrated the recurrence of HFE single nucleotide variants (SNVs) in patients with IE, postulating a possible link between Hemochromatosis genes and erythrocytosis. The most frequent HFE SNVs are C282Y and H63D, reported at allele frequencies of about 13% and 4% in Caucasian countries. HE has also been associated with mutations in genes members of the complex pathway of "oxygen sensing" (EPOR, VHL, HIF-2a and PHD2). To date, 30 mutations have been described in the PHD2 gene, all localized in the catalytic domain, which impair binding to HIF-2a. The PHD2p.C127S variant is frequently observed in Tibetans with D4E in cis (overall prevalence of this haplotype is 88.6% at altitudes above 3000m), in linkage disequilibrium with other missense mutations (in particular HIF-2a/EPAS1). Surprisingly, the combination of PHD2/HIF-2a variants result in a gain-of-function effect that blunts the hypoxic response, providing a molecular mechanism for the observed protection of Tibetans from erythrocytosis at high altitude. In normoxic conditions and in low-landers, the PHD2p.C127S variant may lead to increased erythropoiesis as reported in the literature. Patients and Methods Twenty-three patients with erythrocytosis (21 males and 2 females with a median age of 56 years, range 18-76, Table 1) negative for JAK2 mutations (both V617F and exon 12 variants), and with a bone marrow histology not suggestive of a myeloproliferative syndrome were studied for secondary causes of erythrocytosis using an appropriate algorithm (EPO levels, chest and abdomen imaging, spirometry, venous p50 of HB, arterial blood gas analysis). Since all tests were negative, HE genes mutation analysis was carried out, using Sanger sequencing of EPOR exon 8, the VHL coding region, PHD2 exon 1-3 and HIF-2a exon 12. HFE SNVs were studied using allele-specific real-time PCR. Results Sequencing of HE genes identified 4 carriers of PHD2 variants in 23 patients (17%). One patient had a novel missense heterozygous mutation (PHD2p.I269N). The study of his kindred showed that his sister and one daughter have HE and both carried the same heterozygous mutation of the propositus. Furthermore, his father had died with a diagnosis of PV in the pre-JAK2 era. In contrast, the patient's brother and the other daughter, both with normal Hb and Hct, had wild-type PHD2. Of note, the propositus and his two daughters were heterozygous for H63D in the HFE gene. The patient's pedigree is illustrated in Figure 1. Interestingly, three further patients tested positive for the PHD2 missense heterozygous variant (PHD2p.C127S) previously reported in the Tibetan population, and whose role in patients with erythrocytosis is still unclear. HFE SNVs real-time PCR revealed 7 carriers of the H63D, 1 of C282Y and 1 of S65C SNV in the HFE gene (about 40% of our cohort). Interestingly, two H63D heterozygous patients were a father and his son. They were all males with a median age of 48 years (range 18-64). The prevalence of HFE SNVs in our cohort of patients with erythrocytosis is higher than expected for H63D and S65C for Caucasians (30% vs 13% for H63D and 4.35 vs 1.5% for S65C), while the allele frequency of C282Y was similar to that of the general population. Finally, the patient with the S65C SNV also had the "Tibetan" PHD2 polymorphism. Conclusions In addition to previously known PHD2 gene alterations, we report here the occurrence in HE patients of a novel PHD2 mutation with an autosomal-dominant inheritance likely involved in disease pathogenesis. The milder phenotypic features of this patient's daughter and sister in terms of erythocytosis, may be explained by the childbearing age and the absence of H63D SNV, respectively. The increased prevalence of HFE SNVs in patients with IE may indicate an effect of impaired iron metabolism on erythropoiesis. Our data show that the inclusion of HFE SNVs and oxygen pathway mutational analysis in the diagnostic algorithm of erythrocytosis may help to better define the genetic basis of erythrocytosis. Further studies -including the analysis of molecules involved in iron storage pathway- in larger IE patient cohorts are warranted in order to clarify the link between HFE gene and IE. Disclosures Voso: Celgene: Research Funding, Speakers Bureau.

Introduction. Rituximab has been demonstrated to be effective either as intralesional or as systemic therapy in PCBCL, We report our experience in the treatment of PCBCL with intravenous Rituximab. P atients and Methods From February 1999 to February 2014 we treated 75 patients: 47 Follicle Center Lymphoma, 23 Marginal Zone Lymphoma, 5 Diffuse Large Lymphoma Leg type. The stage was T1 in 38 pts, T2 in 22 pts and T3 in 15 pts. In 24 patient prior treatment included: CHT (11), Radiotherapy (4), Surgery (4) or alpha2Interferon (IFN) (5). Rituximab at dosage of 375 mg/m2 for a minimum of 4 cycles, was administered alone (51 patients) or in association with CHT (13). RT (2) or IFN (3). Results. No patient presented adverse effects during the Rituximab infusion. A reduction of circulating B lymphocytes was observed for 11 months, on the average, without an increased risk of infections. No added toxicity was observed in patients treated with Rituximab plus CHT. Overall response rate was 97,3% (CR 82,6 %, PR 14,6 %). Five–years Overall Survival (OS) was 86,9% with Disease Free Survival of 57%. According to stage OS was in T1 94,3%, in T2 90,5%, in T3 73,6%. (T1+T2 vs T3: p Conclusions. Rituximab is effective and safe in the treatment of PCBCL even in heavily-treated or elderly patients. In our patients only the stage of disease was significant for the prognosis. A higher number of patients are necessary to indicate Rituximab in biological and clinical subsets of patients as a front-line therapy. Disclosures No relevant conflicts of interest to declare.

Although the therapy of acute myeloid leukemia (AML) has remarkably improved over the last 2-3 decades, two thirds of young adults still die of their disease. In elderly adults, who represent the majority of patients with AML, the results are even more unsatisfactory with less than 10% of patients being long-term survivors. Based on this, age is universally recognized as a critical prognosticator affecting outcome and therefore treatment choice. In consecutive series of adult patients with de novo AML, we have repeatedly demonstrated the prognostic role of minimal residual disease (MRD) as detected by flow cytometry. In particular, we have found that a level of MRD ≥ 3.5x10e-4 residual leukemic cells (RLC) at the end of consolidation is associated with a relapse rate of 70-80%. In the present study we evaluated whether the prognostic impact of MRD assessment after consolidation remained unaltered even in age-stratified (< 60 and > 60 years) populations of adult patients with de novo AML. To this end, we analyzed 149 young (median age 46, range 18-60) and 61 elderly adults (median age 67, range 61-78). All patients under study achieved complete remission after an induction therapy of the EORTC/GIMEMA protocols AML10, LAM99P and AML12 (for patients < 60 years) or AML13, AML15A and AML17 (for patients > 60 years). The two cohorts were well balanced in terms of frequency of FLT3-ITD and NPM1 mutated cases. A lower frequency of favorable-risk karyotypes was observed in elderly versus young patients (4% vs 19%, p=0.024). Of 149 younger patients, 105 (70%) underwent stem cell transplantation (SCT) (45 allogeneic, 60 autologous) as compared to 7 (11%) in the older age group (1 allogeneic, 6 autologous), (p= Disclosures: No relevant conflicts of interest to declare.