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Long-term safety and efficacy of eltrombopag in adults with persitent/chronic primary immune thrombocytopenia (ITP) evaluated in EXTEND study, showed a high response rate (80%) but, in the clinical safety study, it was observed that 6% of the patients presented venous and arterial thrombotic events. In addition, in the course of the disease, autoimmune hemolytic anemia (Evans syndrome, ES) may occur and could increase the risk of thrombosis. We report an interesting case of splenic rupture due to massive intrasplenic arterial thrombosis in the course of ES in a patient with chronic ITP treated with eltrombopag. The purpose of this case report is to highlight the potential increase in thrombotic risk that may involve the use of eltrombopag in hemolysis situations in patients with ITP.

Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3-4 >= 5 and abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a moderate agreement was observed between methods when focusing on individual cases (kappa=0.507; P

Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020; Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects. Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts. CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies; univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx). Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98); 31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2). Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L; 27% vs. 21%), and lymphocytopenia (ALC < 1.0 x 109/L; 18% vs. 28%), while others varied between Co1 and Co2 (p Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including therapeutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts; COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented. Disclosures Roeker: American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Scarfo: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; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Eyre:AbbVie: Consultancy, Honoraria, Other: travel support; Gilead: Consultancy, Honoraria, Other: travel support; Janssen: Consultancy, Honoraria, Other: travel support; KITE, AZ, Loxo Oncology at Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Muntañola Prat:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp & Dohme: Honoraria. Leslie:AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Speakers Bureau; Karyopharm: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allan:Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria. Furman:Incyte: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; Oncotarget: Consultancy; Janssen: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Verastem: Consultancy. Pagel:BeiGene, Astrazeneca, Loxo Oncology, Gilead: Consultancy. Hernandez-Rivas:Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Patel:Genentech: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Motta:Roche: Honoraria; Janssen: Honoraria. Lamanna:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Verastem: Research Funding; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Vitale:Janssen: Honoraria. Kamdar:Roche: Research Funding. Österborg:BeiGene: Research Funding; Kancera: Current equity holder in publicly-traded company, Research Funding; Sanofi: Consultancy; Karolinska Univeristy Hospital, Stockholm, Sweden: Current Employment. Hanson:Janssen-Cilag: Research Funding; Gilead: Research Funding; AbbVie: Honoraria. Eichhorst:ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Varettoni:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses; AbbVie: Other: Travel/accommodations/expenses; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Marchetti:Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Takeda: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Munir:F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alexion: Honoraria. Zabalza:Janssen: Honoraria, Other: travel grants; Roche: Other: travel grants; Novartis: Other: travel grants. Janssens:Amgen: Consultancy, Other: travel grants; speaker fees; Abbvie: Consultancy, Other: travel grants; speaker fees; Celgene: Consultancy, Other: travel grants; speaker fees; Janssen: Consultancy, Other: travel grants; speaker fees; Gilead: Consultancy, Other: travel grants; speaker fees; Novartis: Consultancy, Other: travel grants; speaker fees; Sanofi-Genzyme: Consultancy, Other: travel grants; speaker fees; Roche: Consultancy, Other: travel grants; speaker fees. Niemann:AstraZeneca: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Sunesis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Danish Cancer Society: Honoraria, Research Funding; Novo Nordisk Foundation: Honoraria, Research Funding. Perini:Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Abbvie: Speakers Bureau. Patten:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Honoraria. Marasca:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Honoraria. Iyengar:Janssen: Honoraria; Gilead: Honoraria. Ferrari:Abbvie: Honoraria. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Itchaki:Abbvie Inc: Consultancy, Research Funding. Ma:Novartis: Research Funding; Juno: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Bioverativ: Consultancy, Honoraria; BeiGene: Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; TG Therapeutics: Research Funding. Van Der Spek:AMGEN: Other: Teaching activities. Seymour:Seattle Genetics: Research Funding; Merck: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding. Rigolin:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mauro:Roche: Other; Octopharma: Other; Takeda-Shire: Other; Gilead: Other; Janssen: Other; Abbvie: Other. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Levin:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation. Špaček:Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Walewska:AbbVie: Other: sponsored for educational meetings, Speakers Bureau; Janssen: Other: sponsored for educational meetings, Speakers Bureau; Gilead: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Wiestner:Pharmacyclics LLC, an AbbVie Company; Acerta, Merck, Nurix, Verastem, and Genmab: Research Funding; National Institutes of Health: Patents & Royalties: and other intellectual property. Broom:Gilead: Other: Travel support, Speakers Bureau. Kater:Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Ujjani:AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Verastem Oncology: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Atara: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Gilead: Other: travel grants, Research Funding; Abbvie: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Chong:Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Pu:Takeda Pharmaceuticals: Consultancy. Brown:Janssen, Teva: Speakers Bureau; Gilead, Loxo, Sun, Verastem: Research Funding; Abbvie, Acerta, AstraZeneca, Beigene, Invectys, Juno/Celgene, Kite, Morphosys, Novartis, Octapharma, Pharmacyclics, Sunesis, TG Therapeutics, Verastem: Consultancy. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Shadman:Abbvie, Genentech, Astra Zeneca, Sound Biologics , Pharmacyclics, Verastem, ADC therapeutics, Beigene, Cellectar, BMS, Morphosys and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Pharmacyclics, Gilead, Genentech, Abbvie, TG therapeutics, Beigene, Astra Zeneca, Sunesis, Beigene: Research Funding. Foglietta:Janssen: Honoraria; Gilead: Honoraria. Jaksic:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Sportoletti:AbbVie: Honoraria; Janssen: Honoraria. Barr:Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Verastem: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy; Janssen: Consultancy. Ruchlemer:Abbvie Inc: Consultancy, Research Funding. Kersting:Celgene: Other: travel grant; Janssen: Research Funding; Abbvie: Research Funding. Huntington:Pharmacyclics: Honoraria; AbbVie: Consultancy; Novartis: Consultancy; Genentech: Consultancy; DTRM: Research Funding; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; TG Therapeutics: Research Funding. Herishanu:Roche: Honoraria; Sanofi: Honoraria; Medison: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria. Jacobs:TG Therapeutics, Inc.: Research Funding; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; Seattle Genetics: Consultancy; Verastem: Consultancy; Janssen: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Sanofi Genzyme: Speakers Bureau. Portell:BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding; Bayer: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; AbbVie: Research Funding. Rambaldi:Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Astellas: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); University of Milan: Current Employment; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Received travel support., Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support from Gilead.; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Research grant from Amgen Inc.; Omeros: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Advisory board and speaker fees from Pfizer.. Brander:Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding. Rossi:Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Coscia:Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coombs:Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; MEI Pharma: Honoraria; LOXO Oncology: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo:Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bosch:Jansen: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Roche: Honoraria. Stamatopoulos:AstraZeneca: Honoraria; Janssen, Gilead, Abbvie: Honoraria, Research Funding. Ghia:Adaptive, Dynamo: Consultancy, Honoraria; Novartis: Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene/Juno: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Research Funding; ArQule: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria. Mato:Adaptive: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding.

Key Points Patients with FL anti-HBc+ present with worse 10-year PFS and OS.Patients with anti-HBc+ present with a higher frequency of ARID1A mutations and lack of EP300 mutations., Epidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non–Hodgkin lymphoma (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 patients with FL for HBV infection status, clinical features, and gene mutational profile. Anti-HBc was detectable in 16 patients (13.2%), although all had undetectable HBV DNA. Anti-HBcore+ (anti-HBc+) cases presented with older age at diagnosis than anti-HBc− cases (68.1 vs 57.2 years; P = .007) and higher β2-microglobulin (56.3% vs 28.9%; P = .04). All patients included in the study fulfilled criteria for treatment and received therapy with rituximab or rituximab-containing chemotherapy. There were no episodes of HBV reactivation or HBV hepatitis during treatment and/or maintenance. Remarkably, anti-HBc+ patients had significantly lower 10-year progression-free survival (PFS; 12.9% vs 58.3%; P < .0001) and overall survival (OS; 22.0% vs 86.2%; P < .0001), that remained at multivariate analysis. Gene mutational profiling of all cases showed that anti-HBc+ cases had higher incidence of ARID1A mutations and absence of EP300 mutations, 2 key epigenetic regulators in FL. Overall, our study shows that FL patients with resolved HBV infection have a worse outcome independently of other well-known clinical risk factors and a distinct gene mutational profile.

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p

The use of non‐pegylated liposomal doxorubicin (Myocet®) in diffuse large B‐cell lymphoma (DLBCL) has been investigated in retrospective and single‐arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R‐CHOP or investigational R‐COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to, The use of non‐pegylated liposomal doxorubicin (Myocet®) in diffuse large B‐cell lymphoma (DLBCL) has been investigated in retrospective and single‐arm prospective studies. This prospective randomized phase 2 trial of RCOMP versus RCHOP in DLBCL patients ≥60 years and normal cardiac function demonstrated that R‐COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R‐CHOP. However, the use of non‐pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed.

MYC rearrangements (MYC-R) confer unfavorable prognosis to large B-cell lymphomas (LBCL). Because of the low incidence of such genetic alteration, surrogates to screen MYC-R may be useful in daily practice. Previous studies suggested that clone 1A9-1 of LMO2 loss may be a good predictor for the presence of MYC-R in LBCL. The present study examines the utility of LMO2 clone SP51. For this purpose, we have analyzed 20 Burkitt lymphomas and 325 LBCL. Among them, 245 cases were studied prospectively using whole tissue sections, and 100 retrospectively by tissue microarrays. The cohort of CD10-positive prospective cases achieved the best results. Lack of LMO2 SP51 expression predicted the presence of MYC-R with high specificity, accuracy, positive and negative predictive value (PPV/NPV), and positive and negative likelihood ratios (PLR/NLR). Compared with MYC protein expression, LMO2 SP51 obtained significantly higher specificity, accuracy, PPV, and PLR (94%, 91%, 85%, and 14.33 vs 73%, 77%, 56%, and 3.26, respectively), and similar NPV and NLR (92% and 0.22 vs 95% and 0.12). Compared with LMO2 clone 1A9-1, the sensitivity of LMO2 SP51 was lower (79% vs 89%). We conclude that LMO2 SP51 may be a useful marker to screen MYC-R in CD10-positive LBCL.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

We aimed to study the association between occupational exposure to pesticides and chronic lymphocytic leukemia (CLL) in Spain. Occupational exposure to pesticides (four insecticides, four herbicides and two fungicides) was evaluated using a job-exposure matrix for the Spanish population (MatEmESp) among 302 CLL cases and 1567 population controls in five regions of Spain, 2010–2013. Cumulative exposure scores (CES) were obtained by summing across the exposed jobs the product of prevalence, intensity and duration of exposure to each active substance. Principal components analysis (PCA) and logistic regression models adjusted for age, sex, region, education and occupational exposure to solvents were used. Around 20% of controls and 29% of cases were exposed to one or more pesticides. Compared to non-exposed, subjects in the highest tertile (3rd tertile) of CES of insecticides, herbicides, fungicides were more likely to have CLL [OR (95% CI), P-trend; 2.10 (1.38; 3.19), 0.002; 1.77 (1.12; 2.80), 0.12; and 1.67 (1.06; 2.64), 0.10, respectively). Following PCA, the first component (PC1, explaining 70% of the variation) equally led by seven active substances (the insecticide pyrethrin, all herbicides, all fungicides) was associated with a 26% higher odds of having CLL for 1-standard deviation increase in PC1 (95% CI: 1.14 to 1.40). These results confirm previous associations between CLL and exposure to pesticides and provide additional evidence by application groups and active substance. However, more research is needed to disentangle independent effects of individual active substances., Spanish Ministry of Economy and Competitiveness-Carlos III Institute of Health, European Union (EU) PI08/1770 PI08/0533 PI08/1359 PS09/00773 PI11/01403 PI11/02213 PI14/1219 PI15/00966 PI17/01280 RTIC RD06/0020/0095 RD12/0036/0036 SV-09-CLINIC-1, Instituto de Salud Carlos III IJCI-2016-29502, Instituto de Salud Carlos III API 10/09, Obra Social CAJASTUR (SV-CAJASTUR-1), La Caixa Foundation 2010ACUP 00310, Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia 2017SGR1085, Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) PMP15/00007, CIBERONC del ISCIII

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a “real-world” setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a “real-world” setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Insulin‐like growth factor levels and chronic lymphocytic leukaemia Spanish Ministry of Economy and Competitiveness–CarlosIII Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF)–a way to build Europe (PI17/01280, PI11/01810, PI14/01219, PI11/02213, PI15/00966, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, Rio Hortega CM13/00232, SV-09-CLINIC-1, CIBERESP and SAF2016-79347-R) and the Agència de Gestió d’Ajuts Universitaris i de Recerca AGAUR(2017SGR1085, 2014SGR756). The ICGC CLL-Genome Project was funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud CarlosIII (ISCIII), PMP15/00007 and CIBERONC

Introduction Preventable risk factors for chronic lymphocytic leukemia (CLL) remain largely unknown. The aim of this study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and CLL, in the MCC-Spain case–control study. Methods A total of 318 CLL cases and 1293 population-based controls were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on the 2018 recommendations for cancer prevention (on body fatness, physical activity, and diet) was constructed. We used logistic regression analysis adjusting for potential confounders. Results Individuals in the highest tertile of the WCRF/AICR score had an odds ratio for CLL of 1.25 (95 % CI 0.91; 1.73) compared with individuals with low adherence (p-trend = 0.172). Each point increment in the score was associated with an OR for CLL of 1.06 (95 % CI 0.91; 1.23). Analyses by severity of disease did not show significant heterogeneity of effects. Conclusion Overall, our results do not support an association between the WCRF/AICR score and CLL, yet we might have been limited by statistical power and study design to detect modest associations. Further research, ideally with a prospective design, long follow-up, and including additional lymphoma subtypes, is warranted to confirm the impact of composite healthy lifestyle behaviors on lymphoma risk.

Chronic inflammation plays a role in the development of chronic lymphocytic leukaemia (CLL), and diet might modulate chronic inflammation. This study aims to evaluate the association between the dietary inflammatory index (DII&reg, ) and CLL. A total of 366 CLL cases and 1643 controls of the Spanish multicase-control (MCC) Spain study were included. The inflammatory potential of the diet was assessed using the energy-adjusted dietary inflammatory index (E-DII) based on 30 items from a validated semi-quantitative food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for potential confounders. Overall, a modest, non-statistically significant, positive association was observed between CLL and E-DII scores (OR for a one-unit increase in E-DII: 1.05 (CI 95%: 0.99, 1.12), p-value = 0.09 and by tertiles: ORT2vsT1: 1.20 (CI 95%: 0.90, 1.59), OR T3vsT1: 1.21 (CI 95%: 0.90, 1.62), p trend = 0.21). These results were independent from disease severity (p-het: 0.70), time from diagnosis (p-het: 0.67) and CLL treatment received (p-het: 0.56). No interactions were detected. In conclusion, the consumption of a diet with high pro-inflammatory components was not significantly associated with CLL. Changes towards a more pro-inflammatory dietary pattern in younger generations not included here warrant future research.

OBJECTIVE: To evaluate the role of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and a cardiovascular (CV) risk score named FRESCO for predicting anthracycline-induced cardiotoxicity (AIC) in diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 130 consecutive DLBCL patients treated in first-line with anthracycline-containing immunochemotherapy. Competitive risk between NT-proBNP, FRESCO, and time to AIC was considered. RESULTS: Cumulative incidence of AIC was 12.2% and 17.5% at 1 and 5 years, respectively. Median time to development cardiotoxicity was 6.4 months, with half of the cases showing heart failure and the other half silent AIC. Both NT-proBNP levels and FRESCO score were independently associated with higher risk of AIC (P = 0.001 and P = 0.03, respectively). Patients with NT-proBNP ≥600 pg/mL or those with FRESCO ≥4.5% had 3.97 or 2.54 times higher risk of AIC than those with lower values (P = 0.001 and P = 0.048, respectively). According to the previous cutoffs, three groups of patients with a significantly different risk of AIC could be identified (P < 0.0001). CONCLUSIONS: Doxorubicin-containing chemotherapy is associated with increased risk of silent and overt AIC. Baseline NT-proBNP levels and FRESCO CV risk score are accurate predictors of AIC and can identify groups of patients at different risk, in which personalized cardiologic evaluation should be offered.

Chronic lymphocytic leukemia (CLL) has few known modifiable risk factors. Recently, circadian disruption has been proposed as a potential contributor to lymphoid neoplasms' etiology. Serum melatonin levels have been found to be significantly lower in CLL subjects compared with healthy controls, and also, CLL prognosis has been related to alterations in the circadian molecular signaling. We performed the first investigation of an association between night shift work and CLL in 321 incident CLL cases and 1728 population-based controls in five areas of Spain. Participants were interviewed face-to-face by trained interviewers to collect information on sociodemographic factors, familial, medical and occupational history, including work shifts and other lifestyle factors. We used logistic regression models adjusted for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). Seventy-nine cases (25%) and 339 controls (20%) had performed night work. Overall, working in night shifts was not associated with CLL (OR = 1.06; 95% CI = 0.78-1.45, compared with day work). However, long-term night shift (>20 years) was positively associated with CLL (OR(tertile 3 vs . day-work) = 1.77; 95% = 1.14-2.74), although no linear trend was observed (P trend = 0.18). This association was observed among those with rotating (OR(tertile 3 vs . day-work) = 2.29; 95% CI = 1.33-3.92; P trend = 0.07), but not permanent night shifts (OR(tertile 3 vs . day-work) = 1.16; 95% CI = 0.60-2.25; P trend = 0.86). The association between CLL and long-term rotating night shift warrants further investigation.

On behalf of Grupo Español de Leucemia Linfática Crónica (GELLC) and Grupo Cooperativo Español de Citogenética Hematológica (GCECGH)., We analyzed the features of chronic lymphocytic leukemia (CLL) with multiple abnormalities (MA) detected by FISH. A local database including 2095 CLL cases was used and 323 with MA (15.4%) were selected. MA was defined by the presence of two or more alterations (deletions of 13q14 (13q-), 11q22 (11q-), 17p13 (17p-) or trisomy 12 (+12)). The combination of 13q- with 11q- and 13q- with 17p-, accounted for 58.2% of the series, in contrast to 11q- with 17p- (3.7%). Patients carrying MA since diagnosis presented a short time to first therapy(TTFT) (27 months) and overall survival (OS) (76 months). The combinations including 17p- had a shorter OS (58 months) than the ones without 17p- (not reached, p =.002). Patients with a complex-FISH were the ones with worse OS (34 months). MA imply poor prognosis when they emerge at diagnosis, probably due to the high incidence of bad prognosis markers, which may be a reflection of a more complex karyotype.

Predoctoral contract to MS (CIBERESP), Spanish Ministry of Economy and Competitiveness Juan de la Cierva de Incorporación grant IJCI-2014-20900. Spanish Ministry of Economy and Competitiveness - Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) - a way to build Europe [(grants PI17/01280, PI11/01810, PI14/01219, PI11/02213, PI09/1662, PI15/00966, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, Rio Hortega CM13/00232, SV-09-CLINIC-1 and Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP))] and the Agència de Gestió d'Ajuts Universitaris i de Recerca AGAUR (2017SGR1085, 2014SGR756). The ICGC CLL-Genome Project was funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII), PMP15/00007 and Centro de Investigación Biomédica en Red: Oncología (CIBERONC)., Solans, M., Castelló, A., Benavente, Y., Marcos-Gragera, R., Amiano, P., Gracia-Lavedan, E., Costas, L., Robles, C., Gonzalez-Barca, E., Banda, E.L., Alonso, E., Aymerich, M., Campo, E., Dierssen-Sotos, T., Fernández-Tardón, G., Olmedo-Requena, R., Gimeno, E., Castaño-Vinyals, G., Aragonés, N., Kogevinas, M., Sanjose, S., Pollán, M., Casabonne, D.

Introduction Chronic Lymphocytic Leukemia (CLL/SLL) is the most common adult leukemia in Western countries. Although it is mostly an indolent disease it is still incurable and with limited knowledge in relation to its etiology. We aim to confirm and quantify established risk factors for CLL/SLL using a multi-center epidemiological population-based case-control study on CLL/SLL as well as to explore new exposures inconclusively associated with CLL/SLL Methods Using the framework provided by the large MCC-Spain case-control study, we explored established and suggested risk factors associated with CLL/SLL using data collected through a face-to-face interview. We estimated odds ratios (OR) and confidence intervals (CI) adjusted by basic confounders, in 1,845 controls from the general population and 560 CLL/SLL from 5 different Spanish regions. Results Among the established risk factors, CLL/SLL cases were 3 times more likely to report first degree relatives with an hematological cancer (OR = 3.11, 95% CI 2.10 to 4.61) and nearly twice likely to have ever worked in agriculture (OR = 1.70, 95% CI = 1.34 to 2.16). New findings suggest that women with CLL/SLL were more likely to have central obesity (OR = 1.67 95% CI = 1.12 to 2.48). An inverse association was found for current alcohol consumption (p-trend Conclusion We confirmed previous established risk factors for CLL/SLL. Among the new findings, further research of central obesity as preventable exposure and the treatment for type II diabetes are warranted.

Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations [t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G-banding cytogenetics (CGC) [i-del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) [F-del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i-del(13q) and F-del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q-deleted nuclei did not differ from i-del(13q) patients (73% vs. 64%), but both were significantly higher than F-del(13q) (52%, P

INTRODUCTION. Chromosome banding analysis (CBA) is the gold standard to identify complex karyotypes (CK; ≥3 chromosomal aberrations in the same clone). CK are predictors of poor prognosis and treatment refractoriness in patients with chronic lymphocytic leukemia (CLL). Patients with CK (15% at diagnosis) constitute a heterogeneous subgroup with highly variable clinical course. Recent studies that aim to refine CK definition in CLL suggest that ≥5 is the number of anomalies detected by CBA that better predicts an impaired outcome (Baliakas et al, 2019). Molecular techniques as genomic microarrays also detect genomic complexity (GC). A recent multicentric ERIC study (Leeksma et al, ASH 2017) identified that patients with ≥5 copy number alterations (CNA) detected by microarrays are associated with an adverse outcome. However, risk stratification regarding genomic complexity assessed by CBA and microarrays has not been compared. OBJECTIVES. 1. To compare genomic complexity in CLL defined by CBA vs microarrays; 2. To compare risk stratification based on genomic complexity measured by both techniques. METHODS. The study cohort included 293 CLL patients from 16 European institutions (67% males) with available CBA result at diagnosis or prior to first treatment. The cohort was enriched in patients with CK (n=153, 52%). Tumor DNA extracted from peripheral blood (n=254) or bone marrow samples (n=39) obtained at the time of CBA was hybridized to CGH-arrays (n=12) and SNP-arrays (n=281) platforms. Clinically relevant aberrations [11q-, +12, 13q-, 17p-] and CNA ≥5Mb were considered for the anomaly count. Three risk groups were defined using previously suggested cut-off points for CBA and microarrays [non-CK/low-GC: 0-2; low/intermediate-CK/GC: 3-4; high-CK/GC: ≥5 (Baliakas et al, Leeksma et al)]. Groups obtained by both methods were compared and correlated with other clinical and biological data. Time to first treatment (TTT) of patients categorized according to the number of alterations detected by CBA and microarrays was analyzed. RESULTS. Median number of abnormalities detected was 3 (range: 0-19) by CBA and 2 (range: 0-18) by microarrays. When stratified according to previously defined criteria, a moderate agreement was observed between both techniques (κ=0.483, p Regarding the prognostic value of genomic complexity and considering the number of abnormalities detected as a continuous variable, CBA and microarrays showed a similar concordance index (C-index) for TTT (0.615 vs 0.609, respectively). When considering all the abnormalities independently of their size or when lowering the cutoff to 1Mb for those non-CLL abnormalities, similar impact on TTT was observed (C-index=0.593 vs 0.616). The three risk groups defined by each method showed significant differences on TTT (Figure 1, p CONCLUSIONS. 1. CBA and microarrays are helpful techniques for assessing genomic complexity in CLL patients; 2. Risk categories established by both methods have a significant impact on TTT although they show a moderate agreement; 3. Discordant cases are being investigated to refine genomic complexity criteria equivalent by both techniques. ACKNOWLEDGEMENTS. 17SGR437, GLD17/00282, FPU17/00361 Disclosures Rigolin: AbbVie: Speakers Bureau; Gilead: Speakers Bureau; Gilead: Research Funding. Gimeno:JANSSEN: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Bosch:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Cuneo:Amgen: Honoraria; Abbvie: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Background:The isolation of cell-free DNA (cfDNA) evolved the concept of liquid biopsy. Several works have analyzed the presence of cfDNA in lymphomas, especially in diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), however there is limited information regarding the detection of cfDNA in other types of lymphomas or the role of cfDNA detection to monitor disease outcome. Objectives:1.- To analyze the presence of cfDNA at diagnosis of patients with lymphoproliferative malignancies. 2.- To evaluate the change in concentration of cfDNA ([cfDNA]) after treatment in DLBCL patients. Material and Methods:A retrospective study in a single center was performed including 221 adult patients since January 2015 to February 2019 with: DLBCL, HL, marginal zone lymphoma (MZL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma (LPL) and peripheral T-cell lymphomas (TCL). All patients had plasma samples collected at diagnosis that were stored in the institutional biobank (MarBiobank). The cfDNA were obtained from 1 mL of -80°C frozen stored plasma using the MagMax Cell Free DNA isolation kit (Thermo Fisher Scientific). The cfDNA quantification was performed using the Qubit system with the dsDNA high sensitivitykit (Thermo Fisher) and is expressed as ng/mL of plasma. In addition, patients with DLBCL who were treated with rituximab-CHOP/CHOP-like regimens were evaluated for [cfDNA] analysis, pre and post-treatment, and results were compared with PET-CT scan findings. Results: Stored plasma samples at diagnosis were available in 221 patients: DLBCL 82, HL 22, CLL/LPL 13, FL 36, MZL 37, MCL: 11, TCL 10 and others 10 (B-cell lymphoma unclassified, hairy cell leukemia, Burkitt lymphoma). Successful identification of cfDNA was obtained in 95.9% (212/221) of samples. DLBCL patients showed higher [cfDNA] globally and, DLBCL, HL and FL patients showed a higher concentration than MZL who exhibited the lower concentration of all groups (p=0.009; p=0.013 and p=0.002); see table 1. 50 DLBCL patients with a median follow-up since diagnosis of 25.5 (5-51) months were analyzed. Median age was 67 (19-79) years, males 56% (28). IPI distribution: low-risk 28% (14), low-intermediate 26% (13), high-intermediate 24% (12) and high risk 22% (11) cases. Detection of cfDNA was successful in 100% at diagnosis and in 98% (49) cases post-therapy. The mean [cfDNA] at diagnosis was 2.21 (standard deviation- SD: 1.60) ng/mL with a correlation with LDH concentration (p After therapy 86% (43) of patients achieved at least PR (41 complete response), and the mean [cfDNA] for these patients was 1.58 (SD 1.96); patients who showed no response or progressive disease after therapy exhibited higher [cfDNA] 21.25 ng/mL (SD 41.91)(p Conclusions:Isolation of cfDNA was feasible in >95% of lymphoma patients independently of histology or disease stage. Patients with DLBCL exhibited the higher cfDNA concentration which were also correlated with LDH concentrations and high-risk IPI. Kinetics of [cfDNA] is related to response to therapy in DLBCL and also might detect relapse. Even though additional studies are necessary, monitoring of cfDNA may help in management of patients with DLBCL. Disclosures Salar: Roche: Research Funding, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy. Sanchez-Gonzalez:Takeda: Consultancy, Speakers Bureau; Alexion: Speakers Bureau; Gilead: Speakers Bureau; Shire: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Gimeno:JANSSEN: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Bellosillo:Qiagen: Consultancy, Speakers Bureau; TermoFisher Scientific: Consultancy, Speakers Bureau.

Doxorubicin-containing chemotherapy is the standard regimen for elderly patients with aggressive lymphoma. However, many of them cannot receive it due to severe associated comorbidities. Toxicity and efficacy of intermediate doses of nonpegylated liposomal doxorubicin (NPLD) in modified-CHOP regimen ± Rituximab were prospectively analyzed in 35 frail elderly patients (median age: 76 years) with previously untreated aggressive lymphoma with one or more severe comorbidities. NPLD at intermediate doses (30 mg/m 2 ) is effective and well tolerated in these patients. In addition, NT-proBNP levels > 900 ng/ml at diagnosis have demonstrated to be a good predictor for OS and PFS in this cohort of patients.

DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions.

Introduction: Anthracyclines are cytotoxic antibiotics used in the treatment of lymphomas. Myocardiopathy is a well-known toxicity of anthracyclines, and both acute/subacute and late-onset presentations have been described. Early detection of asymptomatic cardiac dysfunction and identification of biomarkers for anthracycline cardiotoxicity risk may be important to prevent irreversible heart damage. Objective: To prospectively evaluate the incidence, time of appearance and clinico-biological variables associated with the development of myocardiotoxicity in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP/R-CHOP-like regimens. Patients and Methods: one hundred and sixty six patients with DLBCL from 05/2004 to 05/2014. Excluded: HIV infection (10), treatment without anthracyclines (21) and other causes (5) (Table 1). Left ventricular ejection fraction (LVEF) determined by high resolution echocardiography and the N-terminal brain natriuretic peptide (NT-proBNP) fragment were done prior initiation of treatment, at the end and every 6-12 months thereafter. Myocardiotoxicity was defined as: LVEF 15% if prior LVEF Results: median age 68 years (IQR: 54-75), 51% male, median NT-proBNP 251.8 pg/mL (IQR: 76.2-560.1), median LVEF 64% (IQR: 60-69%) and median FRESCO scale 4.5 (IQR 2.1-7.2). NT-proBNP was correlated with FRESCO scale, but not with LVEF. With a median follow-up of 64.7 months (95% CI 56.4-73.6) 24 cardiac events were observed (5 clinical CHF + normal LVEF, 7 clinical CHF + LVEF low and 12 low LVEF without clinical CHF). Cumulative incidence of myocardiotoxicity was 8.8% at 6 months (95% CI 5.0 to 15.3), 12.3% at 12 months (95% CI 7.6 to 19.6), 14.2% at 24 months (95% CI 9.1 to 21.9) and 17.6% at 5 years (95% CI 11.6 to 26.1). C statistic for myocardiotoxicity was: FRESCO scale 0.7192 (95%CI: 0.6284- 0.8099) and FRESCO scale+NT-proBNP 0.807 (95%CI: 0.7309-0.8832). Competing risks analysis showed a significantly increased cumulative incidence of myocardiotoxicity in patients with NT-proBNP >600 +/- FRESCO >4.5 (Figure 1). Finally, we performed a computational modeling using 12 Bayesian networks to analyze the connections between demographic characteristics, cardiovascular risk factors, treatment, occurrence of cardiotoxicity and death (Figure 2 illustrates one of the networks). Conclusions: myocardiotoxicity induced by anthracyclines remains an important problem in the daily practice. The FRESCO cardiovascular risk function is useful for predictingmyocardiotoxicity and levels of NT-proBNP improved accuracy myocardiotoxicity risk. We propose that patients with NT-proBNP >600 pg/mL or FRESCO > 4.5 should have a specific cardiologic surveillance and follow-up in cardio-oncology units from the start of their anthracyclin-containing chemotherapy. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION Chemotherapy-induced hepatitis B virus (HBV) reactivation is a well-recognized complication and is a potentially life-threatening condition in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg]-positive). Rituximab has been associated with an increase in HBV reactivation in chronic HBV patients (45%) and even in patients with resolved infection (HBsAg negative and hepatitis B core antibody [anti-HBc]-positive (22%); however, the reported frequency varies among different studies. Current guidelines for management of chronic HBV recommend routine antiviral HBV prophylaxis with lymphoma before starting chemotherapy. In contrast, there is little evidence-based consensus regarding patients with resolved HBV infection. Aim: To analyze the incidence of HBV reactivation and the role of antiviral HBV prophylaxis in lymphoma patients with chronic HBV or resolved HBV treated with chemotherapy, immunotherapy or immunochemotherapy managed according to our institutional HBV guidelines. Secondary endpoints were to analyze the incidence of HBV in this population and HBV guidelines adherence. PATIENTS AND METHODS Lymphoma patients with chronic HBV or resolved HBV in a single center. HBV viral status definitions: Active Chronic HBV infection: HBsAg positive, anti-HBc positive and HBV DNA >2000 IU/mL; Inactive Carriers: HBsAg positive, Anti-HBc positive, HBV DNA undetectable or HBV reactivation was defined as increased serum HBV DNA (≥1 log10), regardless of liver biochemistry or HBsAg status. Institutional HBV guidelines: serum samples were collected at baseline for HBsAg and anti-HBc testing in all lymphoma patients. Patients were evaluated by a hepatologist if any of them fulfilled HBV viral status definition. Baseline at screening and monitoring every 3 months during therapy and up to 24 months after completing therapy (assessment of liver biochemistry, serum HBV DNA, HBsAg and anti-HBs levels). Specific prophylaxis strategies according to HBV status: Group A (Active chronic HBV): treatment for HBV; Group B (Inactive carriers): antiviral HBV prophylaxis; Group C (Resolved HBV): antiviral HBV prophylaxis if rituximab containing-therapy or follow-up only if rituximab-free therapy. HBV antiviral prophylaxis was started before therapy and finished 12 months after completing therapy. RESULTS From January 2012 to January 2015, 227 lymphoma patients received chemotherapy or immunochemotherapy. 142 (63%) patients received rituximab-containing therapy. 43 (19%) patients were anti-HBc positive. Group A: 2 (1%) patients; Group B: 2 (1%) patients; Group C: 39 (17%) patients. 14 (6%) patients have coinfection with hepatitis C virus and 12 (5%) patients co-infection with human immunodeficiency virus (HIV). Adherence to HBV guidelines was 90%. Patients in Group A (n=2) and B (n=2) received antiviral treatment/prophylaxis before starting therapy. In the Group C, 16 (41%) patients underwent only follow-up and 23 (59%) patients received HBV antiviral prophylaxis (lamivudine in 4, entecavir in 8 and tenofovir in 11). Median duration of HBV prophylaxis was 18 months (95% CI: 16-19 months). After a median follow-up of 21 months, 2 patients developed HBV reactivation during lymphoma treatment: 1 from group B (reactivation rate of 50%) and 1 from group C (reactivation rate of 3%). Both patients had received rituximab-containing treatment and both developed HBV reactivation (without hepatitis flare) within the first 6 months after finishing antiviral HBV prophylaxis (delayed HBV reactivation). Outcome was favorable in both patients. Characteristics of HBV reactivation patients are shown in table I. Cumulative incidence of HBV reactivation at 12 and 24 months were 0% and 8%, respectively. CONCLUSION Our strategy of close monitoring patients with chronic HBV or resolved HBV that receive chemotherapy and adding antiviral HBV prophylaxis only in selected patients clearly decrease HBV reactivation. Nevertheless, this strategy may not fully protect patients from late HBV reactivations. Larger validation studies are needed to confirm our data and to establish the best cost-effective strategy in this lymphoma population, especially in the new era of inmunomodulatory drugs of their real involvement in HBV reactivation is unknown. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

Background and objective The optimal treatment of aggressive non-Hodgkin lymphoma (NHL) in elderly patients remains controversial. We aimed to evaluate the impact of age and use of anthracyclines. Patients and method Retrospective analysis of patients with aggressive NHL aged over 70 years old. Results One hundred and twenty-eight patients with a median age of 76 years (70–91). Eighty-eight percent received chemotherapy, and 72% received anthracyclines. The overall response rate was 70%, 51% with a complete response (CR)/uncertain complete response and 19% with a partial response (PR). Overall survival (OS) was 28 months (95% confidence interval 18–78). In the diffuse large B-cell lymphoma group, progression-free survival (PFS) and OS were significantly better in patients who achieved CR versus PR. The use of anthracyclines was associated with CR, the international prognostic index (IPI) was associated with both survival and response, and age showed no association. Conclusions In patients aged ≥70 years with aggressive lymphoma who received chemotherapy, the IPI but not age and the use of anthracyclines showed a prognostic impact. Therefore, in elderly patients with aggressive lymphomas, the use of anthracyclines should be considered and therapeutic decisions should not be based on age exclusively.

Background and objective: To evaluate the relationship between the degree of glycemic control and the features of the disease and glucose-lowering treatment in patients with type 2 diabetes mellitus in Spain. Patients and methods: Cross-sectional epidemiological study in Spain with consecutive sampling. We recorded demographic and clinical variables of patients who were followed up in the center for > 12 months. Results: We analyzed data from 6,801 patients enrolled by 734 specialist and 965 primary care physicians: 97.8% received pharmacological treatment (30.3% monotherapy, 51,4% dual therapy, 16.1% triple therapy and 26.6% insulin). HbA 1c was 7.3 (1.2) % and 40.4% of patients had HbA 1c 15 years) and the type of treatment (52.9% monotherapy, 35.6% dual therapy, 28.0% triple therapy and 25.2% insulin). In the multivariate analysis, insulin therapy (odds ratio [OR] 0.329; IC 95% 0,267-0,405) and the presence of components of metabolic syndrome (hypertriglyceridemia and/or low HDL and/or abdominal obesity (OR 0.728; IC 95% 0,595-0,890) were associated with poor glycemic control. Conclusions: We observed an impairment of glycemic control with the progression of the disease and the complexity of the process and treatment, which in part may be related to the inadequate treatment selection and intensification. © 2011 Elsevier Espana, S.L. All rights reserved.

Gastrointestinal (GI) complications are common side effects related to non-steroidal anti-inflammatory drugs (NSAID) and low-dose aspirin (LDA) use. The guidelines to prevent GI complications establish that patients at high risk should receive gastroprotection. However, different reports have suggested that these strategies are not greatly executed. To determine the prevalence of use of preventive strategies to reduce GI complications in NSAID and/or LDA users in primary care in Spain, we performed an observational, cross-sectional, multicentre study in which primary care physicians from Spain participated. From January 2009 to May 2009, physicians collected demographic, clinical and treatment data from the last visit in 2008 of the first 5 consecutive patients who met the selection criteria. A multivariate logistic regression was carried out to identify independent predictors of the preventive strategies used. A total of 713 primary care physicians included 3357 patients: 68% NSAID users, 19.1% LDA users and 12.9% NSAID/LDA users. 31.5% of patients did not have a risk factor for GI complications, 25.6% had one risk factor and 42.9% had 2 or more risk factors. The overall prevalence of preventive strategy use was 75.8%. The prevalence of gastroprotection use increased with the number of risk factors. The underutilization of gastroprotection in at-risk patients treated with NSAIDs is low and not as marked as those previously reported at the primary care level in other countries. We also found high rates of gastroprotection use in LDA users.

NT-proBNP provides diagnostic and prognostic information in heart syndromes but its role in cancer has not yet been established. The prognostic value of NT-proBNP was prospectively studied in 104 non-Hodgkin lymphoma (NHL) patients treated with chemotherapy. Echocardiography and NT-proBNP were determined prior to treatment. In multivariate analysis, NT-proBNP ≥ 900 pg/ml was the variable with higher risk of death (adjusted hazard ratio 11.1; 95% CI 3.8-32.9; P0.001). The C statistic for NT-proBNP ≥ 900 pg/ml was significantly better than IPI score for prediction of survival. These findings suggest that NT-proBNP ≥ 900 pg/ml could be considered a useful marker for risk assessment in NHL patients treated with chemotherapy.

Background Follicular lymphomas are currently subdivided into grades I, II, IIIa and IIIb. This distinction is, however, questioned.Design and Methods We studied the gene expression profile of 43 follicular lymphomas, 50 B-cell non-Hodgkin’s lymphomas of different histotype, and 20 samples of normal B-lymphocytes in order to assess: (i) the relationship of follicular lymphoma with normal B cells and other B-cell non-Hodgkin’s lymphomas; (ii) whether follicular lymphoma is a unique disease; and (iii) whether follicular lymphoma grade IIIb is closer to follicular lymphoma or diffuse large B-cell lymphoma of the germinal center B-cell type.Results First, we found that the molecular profile of follicular lymphoma is intimately related to that of normal germinal center B cells, irrespectively of the histological grade. Secondly, we observed that follicular lymphoma has a relatively homogeneous gene expresion profile that is distinct from that of other B-cell non-Hodgkin’s lymphoma and does not include discrete molecular subgroups. However, by further clustering samples according to signatures differentially expressed among follicular lymphomas or in follicular lymphomas versus diffuse large B-cell lymphoma, we showed that grade I–IIIa tumors tend to cluster together, while grade IIIb follicular lymphoma constitutes a distinct subgroup, whose molecular signature is closer to that of the remaining follicular lymphomas than to that of diffuse large B-cell lymphoma of the germinal center B-cell type.Conclusions These data support the hypothesis that grade IIIb follicular lymphoma does indeed belong to the group of follicular lymphomas rather than diffuse large B-cell lymphomas, and also suggests a possible revision of the histological grading of follicular lymphomas, with their simple distinction into follicular lymphoma (grade I–IIIa) and follicular lymphoma/large cell (grade IIIb).

Introduction: DLBCL is the more common non Hodgkin lymphoma. This is an aggressive lymphoma that is treated with a standard chemotherapy regimen: R-CHOP. In the last years attempts have been done to improve the outcome both increasing dose-density (CHOP14) or intensity (CHOEP, ACVBP, autologous stem cell transplantation) without obtaining benefit in terms of survival. This has allowed setting R-CHOP administered every 21 days (R-CHOP21) as the standard treatment for DLBCL patients. RDI is an important issue to consider when treating malignancies. Although this a well-known prognostic factor in Hodgkin lymphoma, scarce information has been published in DLBCL. Objective: The purpose of this study is further analyzing the prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14, to evaluate its differential impact when increasing dose density. Material and methods: All patients diagnosed of DLBCL from January-1999 to June-2013 at University Hospital Son Espases were retrospectively identified from Pathology Department registry to avoid selection bias. Only patients treated with R-CHOP21 or R-CHOP14 +/- radiotherapy were included (N=115). To increase the R-CHOP14 cohort we added also all patients treated with R-CHOP14 in the same time period in two additional hospitals (Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona) identified from their Pharmacy registries to avoid selection bias (N=42). Other regimes, consolidations or maintenance were excluded. Table 1 shows main characteristics of the global series (N=157). RDI represents the ratio of the amount of a drug actually administered to the amount planned for a fixed time period. RDI was calculated as previously described. Briefly, RDI of each drug was obtained followed by an average of RDI in CHOP consisting in the sume of RDI of the 3 drugs divided by 3. Main prognostic factors at diagnosis in DLBCL were obtained, including international prognostic index (IPI) factors. Evaluations were carried out following standard guidelines. Results: Overall response and complete response rates were similar in both groups:86% and 76% for R-CHOP21 and 94% and 74% for R-CHOP14(p=0.17 and p=0.85, respectively). Median follow-up for alive patients was 68 months (4-156). There were no differences between the two cohorts in terms of either OS or PFS (Figure 1). In the R-CHOP21, both a reduction higher than 15% in RDI [RR 7.41 (2.51-21.83); (p Conclusions: Overall in our series there were no differences in terms of response or survival between patients treated with R-CHOP21 or R-CHOP14. A higher rate of RDI reduction was observed in the R-CHOP14 group. However, the impact of RDI reductions on response and survival was only observed in the R-CHOP21 group but not in patients treated with R-CHOP14. We can conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions. Table 1. Main clinical characteristics of the patients. R-CHOP21 group(n=74) R-CHOP14 group(n=83) P Age (median & range) 65 (25-88) 55 (15-79) 0.005 Sex (M/F) 34 (46%) / 40 (54%) 51 (61%) / 32 (39%) 0.056 ECOG PS > 1 17 (23%) 18 (22%) 0.85 Ann Arbor stage III-IV 40 (54%) 48 (58%) 0.75 B-symptoms 25 (34%) 26 (31%) 0.86 Elevated LDH 33 (46%) 40 (49%) 0.75 > 1 extranodal site 8 (11%) 19 (23%) 0.057 Bulky disease 23 (31%) 34 (41%) 0.24 R-IPI unfavorable 24 (32%) 26 (32%) 1 NCCN-IPI: - Low - Low-intermediate - High-intermediate - High 9 (13%) 27 (39%) 26 (38%) 7 (10%) 17 (21%) 35 (44%) 24 (30%) 4 (5%) 0.31 Elevated Beta-2-microglobulin 32 (49%) 31 (39%) 0.24 Radiotherapy 27 (36%) 27 (32%) 0.62 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

BACKGROUND Somatic mutations in the myeloid differentiation primary response gene 88 (MYD88) have been described in B-cell lymphomas, including DLBCL. Our group has confirmed the remarkable site-specific occurrence of MYD88 mutations at some immune-privileged locations and, in addition, has described that DLBCL patients are at high risk of progression and death after first-line treatment, with independence of other well-known clinical prognostic factors (Leukemia 2014). AIMS To further analyze the clinical responsiveness and outcome after second-line treatment in DLBCL patients carrying MYD88 L265P. METHODS A series of 175 patients with DLBCL diagnosed at our institution between 2000 and 2013 were included. Inclusion criteria were: full clinical data available, treatment with remission intention, enough material for DNA extraction and absence of HIV infection. The presence of MYD88 L265P mutation was assessed by allele-specific oligonucleotides (ASO)-PCR in DNA samples extracted from FFPE tissue. RESULTS In 129 patients (74%) treatment consisted on rituximab plus CHOP or CHOP-like schedules, while the remaining cases received other treatments depending on their clinical requirements. With a median follow-up time of 57 months, progression free survival (PFS) at 5 years after first-line treatment was 57%. Twelve of these patients (9.3%) had MYD88 L265P mutation, and these patients had a significantly worse PFS that patients who did not (18% vs 59%, p=0.018). Overall survival (OS) at 5 years after first line treatment was 65% (17% vs 72%, with vs without MYD88 mutation, respectively; p=0.001). We further analyzed the outcome after second-line treatment in 32 cases: 6 patients had refractory disease (0 with MYD88 mutation) and 26 patients were in first relapse. Three out of 5 patients carrying MYD88 mutation and 25 out of 27 patients without MYD88 mutation were treated with chemotherapy. Only one out of 5 cases (20%) with MYD88 mutation responded to second-line therapy whereas response was observed in 16 out of 27 cases (59%) without MYD88 mutation(p=0.106). PFS at 4 years from starting second-line therapy was 0 % in cases with MYD88 DLBCL and 34% in those without MYD88 mutation (p=0.092). Moreover, OS at 4 years from starting second-line therapy was 0 % in cases with MYD88 DLBCL and 37% in those without MYD88 mutation (p=0.019)(Figure 1). CONCLUSION Our study shows that MYD88 L265P in DLBCL patients is not only associated to worse respond after first -line therapy, but also to a very poor response to second-line therapy, and consequently to a dismal outcome. New treatments are urgently needed for these patients. Acknowledgments: This study was supported in part by 2014SGR567 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

A higher JAK2 V617F-mutated clone is observed in platelets than in granulocytes from essential thrombocythemia patients, but not in patients with polycythemia vera and primary myelofibrosis

9033 Background: The rapid microbiologic diagnosis in the course of fever of unknown origin plays an important role for the appropriate treatment in neutropenic patients. Blood culture helps identi...

Abstract 2003 Background: Tumor microenvironment has been shown to play a critical role in the biology and treatment response of some types of non Hodgkin's lymphomas. The significance of the presence of Treg cells (FOXP3+) in MALT lymphomas of the stomach remains unknown. The main aim of this study was to analyze by immunohistochemistry the presence of Treg cells in the microenviroment of gastric MALT (gMALT) lymphomas at the time of diagnosis and during follow-up after treatment, and to evaluate their possible impact in outcome. Methods: Patients were included in the study if they had gMALT lymphoma diagnosed according to the 2008 WHO criteria and diagnostic paraffin-embedded blocks were available for review. Thirty-three patients met the criteria for inclusion in the study. Sections were immunostained for CD20, CD3, CD4, CD8, CD68, FOXP3, PD-1, bcl-10 and Ki67. t(11;18) was studied by FISH and/or PCR and t(1;14) by FISH. Clonality study of the B cell receptor was done according to the BIOMED-2 protocol. The number of CD20+ tumor cells and FOXP3+ infiltrating cells was quantified using a micrometric ocular (WPK 10 × mn) that has a 10 mm linear scale divided to 100 parts. Results: The median age was 63 y (range 32–83) with 52% being male. Stage: I in 66%, II in 25% and IV in 9%; B-symptoms in 6%. Translocation t(11;18) was present in 9 (27%) pts and 2 additional cases had strong nuclear expression of BCL-10 without t(11;18) or t(1;14). At diagnosis, the mean (± standard deviation) number of CD20+ tumor cells and FOXP3+ infiltrating cells was 680±232 cells/cm2 and 30±29 cells/cm2, respectively. The mean number of CD20+ tumor cells and FOXP3+ infiltrating cells was similar between gMALT with or without t(11;18). Number of treatments analyzed was 37 (treatment not available in 2 pts and 5 pts received more than 1 treatment). Treatment regimens included: eradication therapy (n=11); interferon+ribavirin (n=1); single or combined agent chemotherapy without rituximab (n=5); rituximab alone or CHOP-like with rituximab (n=4); fludarabine (n=8); fludarabine or bendamustine with rituximab (n=8). The first response evaluation showed an overall clinical response rate of 84% (CR 76%) with persistence of residual disease by histology or molecular (IGHV) studies in 31% and 56%, respectively. Overall, the mean (±SD) CD20+ tumor cells and FOXP3+ infiltrating cells was significantly reduced after treatment (730±208 vs 285±343, p Conclusion: Based on these preliminary findings, there is a significant change of CD20+ cells and moderate reduction of Treg cells in responding patients after treatment for gastric MALT lymphoma. Interestingly, regimens with fludarabine or bendamustine with or without rituximab result in quicker and deeper reduction of CD20+ tumor cells while infiltrating FOXP3+ cells are only moderately reduced. Disclosures: No relevant conflicts of interest to declare.

Abstract 4752 BACKGROUND CHOP ± Rituximab ( R) is the standard regimen for elderly patients (pts) with aggressive lymphoma but many of them are not suitable for it due to severe associated comorbidities. The aim was to evaluate retrospectively the efficacy and safety of a modified-CHOP (with reduced dose non-pegylated liposomal doxorubicin (NPLD) ± R in elderly pts with clinically aggressive lymphoma not tributary to standard anthracycline-containing chemotherapy. PATIENTS AND METHODS Retrospective analysis of 30 pts (16M/14W). Median age 76 years (60-88). Stage III-IV: 19 pts (58%). IPI 3-5: 16 pts (49%). Median baseline left ventricular ejection fraction (LVEF): 63% (33-80). Median NT-proBNP determination: 1431 ng/L (60-9120), 14 patients had NT-proBNP>900. All patients had one or more severe comorbidities. Schedule: NPLD 30mg/m2 (d1), cyclophosphamide 750mg/m2 (d1), vincristine 1.4mg/m2 (d1), prednisone 100mg/d (d1-5) ± R 375mg/m2 (d1) + Pegfilgrastim (d2) every 21 days. RESULTS Median follow-up time was 18 months. Median number of cycles was 4 (range 1-6). Complete response (CR/uCR): 24 pts (73%), Partial response: 4 pts (12%). Two pts progressed during chemotherapy and 10 pts relapsed during follow-up (5 of them dying with active disease). Overall Survival (OS) at 12 and 24 months was 76% (95%CI 61-91) and 70% (95%CI 49-91), respectively. Progression-free survival (PFS) at 12 and 24 months was 65% (95%CI 49-81) and 55% (95%CI 32-78), respectively. A total of 154 cycles were administered. 52% of patients showed grade III-IV neutropenia and 33% of them required hospital admission for febrile neutropenia. LVEF neither NT-proBNP value was significantly different before and after treatment with one patient showing an important improvement in his LVEF. Multivariate analysis recognized NT-proBNP determination >900ng/L as the most negative important factor in OS and PFD. CONCLUSION Disclosures: No relevant conflicts of interest to declare.

9569 Background: NT-Pro BNP provides diagnostic and prognostic information in many heart syndromes, but its role in oncologic patients is not established. Methods: We studied the association between NT-ProBNP levels and the risk of major toxicity associated with chemotherapy and death from all causes in 116 consecutive patients with lymphoma treated with curative intent. High resolution ultrasound echocardiography and serum NT-ProBNP levels were prospectively done previous the start of chemotherapy. Charlson Comorbidity Index was retrospectively calculated. A major toxicity event was defined as: when chemotherapy had to be discontinued, when chemotherapy had to be changed to a less intensive regimen, and treatment-related death. Results: High blood levels of NT-proBNP were associated with previous cardiologic history but not with left ventricular ejection fraction. With a median follow-up of 16 moths (0–49 months), 25 patients had a major toxic event with first line chemotherapy and 16 had died at last follow-up. The threshold of NT-ProBNP with better predictive accuracy for major toxicity-free and overall survival was 900 pg/mL. Patients with levels of NT-proBNP greater of 900 pg/mL had an adjusted hazard ratio (HR) for major toxicity after first-line chemotherapy for lymphoma of 6.4 (95%CI, 2.7–15.1). Two additional independent factors predicting higher major toxicity associated with chemotherapy were albumin < 3.5 g/mL (HR 3.5, P=0.008) and number of extranodal sites ≥ 2 (HR 3.1, P No significant financial relationships to disclose.

Introduction: High blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a sensitive indicator of cardiac abnormalities, have been associated with poor outcome in patients with amyloidosis. However, its clinical value in lymphoma is unknown. Aim: To assess the value of NT-proBNP as a prognostic variable for survival in patients with lymphoma treated with chemotherapy with curative intent. Patients and methods: Clinical heart examination, evaluation of cardiovascular risk factors, determination of NT-proBNP (ECLIA; Roche) blood levels and high resolution ultrasound echocardiography were done at diagnosis. Clinical variables related with patient characteristics, lymphoma risk and cardiovascular risk were analyzed. Results: 117 consecutive pts have been analyzed: median age: 63 years (range: 18–88); male: 56%; NHL: 80%; HL: 20%; ECOG/PS ≥2: 29%; III–IV: 56%; B-symptoms: 16%; LDH >1 nv: 34%; b2-microglobulin >1 nv: 57%; albumin 900, ECOG/PS ≥2, LDH >1 nv, b2-microglobulin >1 nv, albumin < 35 g/L, haemoglobin 60. In multivariate analysis, factors predicting for survival were NT-proBNP >900 (HR 15, 95%CI: 3.9–57.8) (p Conclusions: NT-proBNP >900 pg/mL is the strongest prognostic factor for survival in patients with lymphoma following treatment with curative intent. NT-proBNP is an easy, fast, widely available and well-standardized parameter that could be useful in addition to other well-established prognostic indexes.

BACKGROUND: CHOP± Rituximab regimen is the standard regimen for elderly patients with aggressive lymphoma. However, many of these patients present formal contraindication for this type of treatment due to severe associated comorbidities. The aim of the study is to retrospectively evaluate the safety and clinical profile of a modified CHOP (with low dose non-pegylated liposomal doxorrubicin) ± Rituximab in elderly patients with clinically aggressive lymphoma which are not tributary to standard chemotherapy. PATIENTS AND METHODS. Retrospective analysis of 15 consecutively patients (pts) with previously untreated aggressive lymphoma. Gender: 9 men/6 women; median age: 76 years (62–85y). 6 pts had stage I–II (IPI=1–2) and 9 pts stage IV (IPI=2–5). Median baseline left ventricular ejection fraction (LVEF) was 60.2% (31–80%). Comorbidities: active chronic liver disease (1 pt), severe chronic obstructive pulmonary disease (3 pts), severe cardiomiopathy (4 pts) and others (7 pts). Schedule: non pegylated liposomal doxorubicin 30 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg/d d1-5 ± rituximab 375mg/m2 d1) every 21 days, as a first line therapy. Pegfilgrastim was used on day 2 at standard dose. RESULTS. Nine pts are evaluable for efficacy at the time of this report (2 pts died early due to infectious complications and are not evaluable for response). Median number of cycles was 4 (range 4–6). Total number of cycles administered was 43. A complete response (CR) was achieved in 8 pts (88.8%) and partial response in 1 pt (11.1%) after chemotherapy. CR was achieved in this last patient after involved field radiotherapy. Two pts have relapsed during follow-up, all dying with active disease. OS at 12 months: 70% (CI95%: 42–98%) and PFS at 12 months: 60% (CI95%: 30–90%), with a median time of follow-up for surviving pts of 18 months (4–35 m). Treatment was well tolerated with grade III–IV neutropenia was 39.5% with 14% episodes of febrile neutropenia. No other relevant toxicities were observed. Of note, median LVEF was not significantly different between before and after treatment with one patient showing a clinical significant improve in his LVEF. CONCLUSION. This preliminary data indicate that low dose non-pegylated liposomal doxorubicin in modified CHOP regimen was active and well tolerated in patients with formal contraindications to standard therapy due to severe comorbidities. Further exploration of this regimen administered every 14 days is warranted.

Introduction. Recently, the JAK2V617F mutation has been reported in the majority of PV patients as well as in a variable percentage of ET and IMF patients. Some authors have reported a high correlation of JAK2 mutation with PRV-1 overexpression and the formation of EECs. In the current study we have analyzed the pattern of positivity of these three biomarkers in a cohort of Ph-negative MPD patients. Patients and methods. 103 Ph-negative MPD patients (58 ET, 37 PV and 8 IMF) from a single institution were studied. Patients were diagnosed according to the PVSG and Barosi criteria. EEC formation was determined at diagnosis. At the time when PRV-1 and JAK2 mutation were analyzed 29/103 patients were receiving platelet-lowering therapy ± ASA, 26/103 patients only received ASA and 48/103 received no specific treatment. PRV-1 expression was quantified by real-time reverse transcriptase (RT)-PCR in RNA from granulocytes. Analysis of JAK2V617F was performed by direct sequencing using granulocyte RNA. Results. JAK2 mutation was observed in 21/58 ET (36.2%), 30/37 PV (81.1%) and 5/8 IMF (62.5%). PRV-1 was overexpressed in 25/58 ET (43.1%), 35/37 PV (94.6%) and 6/8 IMF (75%) and EECs formation was seen in 31/58 ET (53.4%), 34/37 PV (91.9%) and 6/8 IMF (75%). All markers were simultaneously positive (group A) in 43/103 patients (41.7%), concurrently negative (group B) in 25/103 patients (24.3%) and both positive and negative markers (group C) were observed in 35/103 patients (34%). In group A, 65% were PV patients, 26% were ET patients and 9 % were IMF patients. In group B, 8% were PV patients, 84% were ET patients and 8 % were IMF patients. In group C, 20% were PV patients, 74% were ET patients and 6 % were IMF patients. Regarding diagnosis, 76% of PV and 50% of IMF patients belonged to group A, whereas the majority of ET patients (45%) pertained to group C (table). When comparing ET and PV, a significant difference was observed (p Conclusion. These results show that, although a good correlation has been observed for the simultaneous expression of these three biomarkers, differences in the pattern of positivity, specially in ET, indicate that not all Ph-negative patients share the same pathogenetic mechanisms and point to other coexisting genetic abnormalities. Diagnosis ET PV IMF All markers positive (group A) 11 (19%) 28 (76%) 4 (50%) All markers negative (group B) 21 (36%) 2 (5%) 2 (25%) Positive and negative markers 26 (45%) 7 (19%) 2 (25%) Total 58 37 8