Search

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.

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. In this retrospective multicenter study, conducted by ERIC, the European Research Initiative on CLL, we assessed the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.Methods: The study included patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021.Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 518 were defined as having severe COVID: 162 were admitted to the ICU while 356 received oxygen supplementation outside the ICU. Most patients (90%) were receiving thromboprophylaxis. During COVID-19 treatment, 8.8% developed a thromboembolic event, while 4.8% experienced bleeding. Thrombosis developed in 20.5% of patients who were not receiving thromboprophylaxis, but only in 8.1% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (11.1% vs. 4.2%, respectively) and in elderly. In multivariate analysis, peak D-dimer level was a poor prognostic factor for thrombosis occurrence (OR=1.020, 95%CI 1.006‒1.033), while thromboprophylaxis use was protective (OR=0.194, 95%CI 0.061‒0.614). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR=1.055, 95%CI 1.013-1.103 and OR=2.490, 95%CI 1.044-5.935, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

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

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.

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Background: Ibrutinib is a first-in-class oral inhibitor of Bruton Tyrosine Kinase (BTK) approved for the treatment patients with CLL who have received at least one prior therapy (R/R) or Treatment Naïve (TN) with del17p. Ibrutinib has been showed to improve progression free survival (PFS) and overall survival (OS) even in presence of del17p. Moreover there is a good tolerability profile such as to not lead to frequent and permanent interruption of therapy.Methods: In 131 CLL/SLL patients (including previously treated and untreated with del17) from eight different hematologic centers of REP (Rete Ematologica Pugliese) Ibrutinib 420 mg once daily was administrated until disease progression or unacceptable toxicity. PFS, OS and Overall response rate (ORR) were calculated. Kaplan Meier method was used to estimate PFS/OS and differences in survival times between groups were assessed with a log-rank test.Results: Among 131 pts, 9 (6.9%) received Ibrutinib as first line therapy (TN) and 122 (R/R) received prior therapies before Ibrutinib (39.7% BR, 18.3% FCR and other treatments); 90% (1-2) lines of therapy, 8% (3-4) lines and 2% more than 5. Median age of the 131 pts with CLL/SLL was 65 y (range, 28-84) with 50% ≥65 y.ECOG Performance Status was observed in 108 pts (0, 56%; 1, 40%; 2, 4%). FISH analysis was performed in 85/131 pts (65%) and some patients had more than one deletion. Among these, 42% had del17p (TN 100% and R/R 36%) and for the remaining R/R was 16% del13q, 4% del11q, 7% trisomy12 and in the others no abnormalities were found. Unmutated and mutated IGVH was performed in 78/131 patients (60%), 63% and 37% respectively. The ORR was 80% (complete response [CR], 10%) for all-treated pts (TN: 86%, R/R: 77%) and for R/R pts with del17p the ORR was 61%.With a median time on study of 17 months (range, 1-45), median PFS was not reached for all TN or R/R patients and the estimated PFS at 30 months was 66,7% for R/R patients. We exclude from our further analysis 9 TN patients because of the small sample size and the lack of events in a median follow up of 15 months (range, 3-24). In 122 R/R pts, median PFS was 39 months for pts with del17p and median PFS was not reached for pts without abnormality (overall logrank p=0.543). At 30 m the estimated PFS was 65.1% for del17p pts and 80.4% for no abnormality pts . Median OS was not reached for 122 R/R patients and the estimated PFS at 30 months was 72.7%. Median OS was not reached in pts with and without del17p (overall logrank p=0.807) with an estimated OS at 30 months of 81.7% and 90.2% respectively.In 47% of all treated patients adverse events (AEs) with grade ≥3 were neutropenia (16%), hypertension (12%), atrial fibrillation (3%), anemia (3%), diarrhea (2%). With a median follow up of 17 months 80% of pts remain on Ibrutinib treatment.Conclusions: In our real life experience with data from REP, Ibrutinib single agent demonstred to be effective. In R/R patients, with a median time on study of 17 months, the estimated PFS at 30 m was 66.7%. The differences in PFS between patients with and without del17p was not statistically significant (p=0.543) but at 30 months the estimated PFS was lower in del17p pts than in no abnormality pts (65.1% vs 80.4%).The treatment was well tolerated with AEs of grade ≥3 in a low percentage (36%) that did not result in treatment interruptions in the most of cases. Clearly, these results will require longer follow up time to be further confirmed. Disclosures No relevant conflicts of interest to declare.

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine–rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008–2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43–86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity

BACKGROUND: The combination schedule of rituximab, fludarabine and cyclophosphamide is considered the standard therapy for fit and young untreated chronic lymphocytic leukemia (CLL) patients. However, although this therapy improves progression free survival (PFS) and overall survival (OS), it has been associated with increased toxicity: 76% of the patients experienced at least one grade 3 or 4 event. Recently, encouraging clinical results in terms of safety and efficacy have been obtained using bendamustine in combination with rituximab (R-B) in untreated CLL patients. PURPOSE: We performed a multicentre retrospective study to assess safety and efficacy of R-B in a large group of untreated CLL patients. METHODS: One hundred and thirty six untreated CLL patients were recruited from 16 Italian Institutions and included in the present analysis. The median age was 69 years (range 43–85), with 49.3% of patients older than 70 years; 53.7% of cases were male. All patients had active disease as defined by the NCI-WG, and 27.2% were at Binet stage C. FISH data, available in 86/136 cases, identified a del(17p) in 5.1% of the patients and del(11q) in 5.9%. Sixty-four patients (47.1%) had a creatinine clearance ≤70 mL/min. Fifty-six % of cases showed a WHO performance status (PS) of I-II and 61% a CIRS comorbidity index >0. RESULTS: Among the 136 patients, 90 cases (66.2%) received B at the dosage of 90 mg/m2 on day 1 and 2 every 28 days, the remaining 46 cases received B at the dosage of 70 or 80 mg/m2. R was administered at the dosage of 375 mg/m2 on day 1 of all cycles in 59.6% of cases, while 40.4% received 375 mg/m2 on day 1 of the first cycle and 500 mg/m2 on day 1 of the other cycles. A total of 725 cycles were administered with a median number of 6 cycles per patient. Eighteen patients (13.2%) required early discontinuation of therapy before the sixth cycle for serious infections (n=7), persistent hematological toxicity (n=5), grade 4 dermatological toxicity (n=3), withdrawal of consent (n=2), hypersomnia and depression (n=1). Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 25.8%, 25.8%, and 16.2% of patients, respectively. Grade 3 or 4 severe infections occurred in 6.6% of patients. The overall response rate (ORR) was 93.4%, 48 patients (35.3%) achieved a complete response (CR), 79 (58.1%) a partial response (PR), 8 (5.9%) a stable disease (SD) and in 1 patient (0.7%) no response assessment was performed due to death prior to terminating therapy. In the high-risk group with del17p, 5/7 (71.4%) cases achieved a PR and 2 a SD. Age >70 years (P=0.026) and del17p (P=0.007) were the only two parameters significantly associated with a lower response rate, while del11q and unmutated IGHV, as well as creatinine clearance 0 did not seem to impact on achievement of response. The only parameter predictive of the probability of achieving a CR was an age CONCLUSIONS: The clinical practice of the Italian centers taking part in the study confirms that chemoimmunotherapy with R-B was an effective and well-tolerated treatment for untreated CLL patients. In patients with del17p the therapy appears to be less efficacious. Disclosures Off Label Use: Bendamustine in diffuse large B-cell lymphoma. Zinzani:Genentech, inc.: Membership on an entity's Board of Directors or advisory committees.

Introduction. Multiresistant (MR) bacteria colonization is considered predictive of related bloodstream infections (BSI), which are worrisome among hematological patients (pts). Few data are available about the actual incidence of MR colonization and the probability of developing a BSI in this population. A multicentric prospective observational study has been carried out within the SEIFEM group, with the aim of detecting the incidence of MR bacterial colonization and the probability of developing MR BSI in hematological pts. Patients and Methods. Between March 1st and August 31st 2015, all pts with a hematological neoplasm admitted to 18 Italian Centres participating to SEIFEM were screened for MR colonization with a rectal swab; cultures of other sites were performed if clinically indicated. Patients showing MR bacterial colonization were recorded in a database where the occurrence of any BSI was correlated with age, gender, type and phase of disease, stem cell transplantation (SCT), presence of invasive devices, type of colonizing bacteria. Results. During a 6-month period, 189 pts with MR colonization were observed. Incidence was 8.9% among all admissions (189/2122). Median age was 59y (range 0-89) and M/F ratio 116/73. Eighty-two pts were affected by acute leukemia, 75 by lymphoma, 24 by myeloma, 6 by chronic myeloproliferative/myelodysplastic syndromes and 2 by aplastic anemia. Forty-four pts underwent SCT (28 autologous and 16 allogeneic). Vancomycin resistant enterococci (VRE) were responsible for colonization in 15 (7.9%) pts, extended spectrum beta-lactamases producing (ESBL-P) enterobacteria in 80 (42.3%) and carbapenemase producing (CP) Gram-Negative Rods (GNR) in 108 (57.1%). Thirteen of 14 pts with multiple colonizations had both ESBL and carbapenemase producing enterobacteria. Multivariate analysis of risk factors for type of MDR colonization showed that a complete hematologic remission was associated to ESBL-P enterobacteria colonization, but protective for CP strains (OR 2, 1.1-3.7, p=0.02 and 0.43, 0.23-0.79, p=0.006, respectively). Overall, 62 pts (32.8%) colonized with MR bacteria developed at least one BSI during the period of observation; 36 of them (58.1%; 19% of the whole series) developed BSI by the same pathogen (MRrel-BSI) (2 VRE, 14 ESBL-P E. coli, 2 ESBL-P K.pneumoniae, 1 ESBL-P E. aerogenes, 12 CP K. pneumoniae, 3 CP P. aeruginosa and 2 CP Acinetobacter spp). The rate of MRrel-BSI according to antibiotic resistance was 13.3% for VRE colonization, 19.5% for ESBL-P enterobacteria and 17.6% for CP GNR. CP K. pneumoniae, but not other CP enterobacteria, was predictive of MRrel-BSI (26.7%). In 82% of cases, MRrel-BSI occurred during neutropenia. At multivariate analysis of predictors of BSI, a relapsed/refractory hematological disease was associated to MRrel-BSI (OR 3.1, 1.4-6.7, p=0.005). Unrelated BSI were also observed in 32 pts (51.6%; 16.9% of the whole series), including 6 MR BSI (2 CP P. aeruginosa, 3 CP K. pneumoniae and 1 VRE). After a median follow-up of 80 days (range 0-270), 25 pts died (13.2%). Three-month overall survival (OS) of the entire cohort was 86%±2.9SE, being significantly lower for pts colonized with VRE (71%) and CP (82%) in comparison with those colonized with ESBL-P bacteria (97%, p=0.0018 and 0.0043 respectively) (Fig.1). Death was attributable to CP GNR related BSI in 5 pts and to VRE related BSI in 1. Multivariate analysis showed that CP GNR related BSI (OR 8.3, 2.2-30.5, p=0.001) and VRE related BSI (OR 87.9, 1.1-675.9, p=0.04), together with intensive care unit admission (OR 50.6, 4.5-570.9, p=0.001) were independent predictors of mortality at 30-days from known colonization, whereas having disease in complete remission was protective (OR 0.02, 0.001-0.43, p=0.01). Conclusions. Incidence of MR colonizing bacteria, particularly ESBL-P and CP GNR, affects nearly 10% of italian hematological cancer pts and results in a MRrel BSI in about one fifth of cases, mainly during neutropenia. MRrel-BSI are responsible for more than 50% of BSI observed in MR colonized pts and are significantly more frequent in relapsed/refractory hematologic disease. VRE and CP GNR colonizations but not ESBL-P are associated to lower OS and predict for a higher fatality of related BSI. Among CP enterobacteria, only K. pneumoniae is associated with MRrel-BSI. Empiric antibiotic treatment should be better tailored taking into account these results. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The aim of this study was to show a lower incidence of febrile episodes in multiple myeloma patients receiving lenograstim vs. filgrastim after high-dose cyclophosphamide for stem cell mobilization. Patients treated with cyclophosphamide were randomly assigned to receive filgrastim or lenograstim. Primary endpoint was the incidence of febrile episodes. 5.1% patients developed a febrile episode, 9.1% with filgrastim and 1.1% with lenograstim. Lenograstim group presented a significantly higher absolute CD34+ cell number compared with the filgrastim group but no differences were detected for collection efficacy. The study demonstrated a lower incidence of febrile episodes with lenograstim compared to filgrastim.

Introduction: Incidence of fungal infections is reducing in the last years due to wider use of effective antifungal prophylaxis. On this basis, we evaluated clinical characteristics and outcome of patients (pts) with hematological malignancies (HMs) and fungal bloodstream infections (FBSI). Patient and Methods: This retrospective/prospective study gathered consecutive documented FBSI observed among HMs diagnosed between January 2011 and June 2015 in 19 Italian Hematology Departments that refer to SEIFEM (Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne) group. Results: We collected overall 100 patients including retrospective pts and those observed in the first six months of the prospective study with FBSI among 16 centers; further 3 centers reported no cases of FBSI. Regarding patients' characteristics male/female ratio was 1, median age was 55 yeras. (IQR 18-88). Two-third of FBSI were detected in AML (43 - 43%) and NHL (27 - 27%); the remaining pts were affected by ALL (9 - 9%), MM (6 - 6%), MDS (5 - 5%), MDS/MPN (5 - 5%), CLL (3 - 3%) and HL (2 - 2%). Thirty-five pts had FBSI at the onset of HM or after the first induction, 47 after treatment for refractory/relapsed disease, 13 when in remission, 28 pts during transplant procedures (17 from allogeneic donor, 11 from autologous cells). Fifty-nine pts were receiving antifungal prophylaxis at FBSI breakthrough: 26 posaconazole, 16 fluconazole, 6 itraconazole, 3 amphotericin B, 3 caspofungin, 1 voriconazole, and 4 combination of amphotericin B/azoles; 4 pts were treated with secondary prophylaxis after previous fungal infection. Eighty-nine pts had a central venous catheter. Eighty-four pts presented a neutrophils count < 500/mmc for a median time of 7 days before FBI onset (0-70 d); 50 pts received steroids and other 17 immunosuppressive treatment for allo-HSCT. Yeasts were the most common agent detected. Candida spp. represent the most represented yeast, counting for 77% of all infections; (21 albicans and 56 non albicans); 8% of FBI were due to 8% Geotrichum, 3% Trichosporon and 2% Rhodotorula, Molds were rare but not infrequent: 8% were caused by Fusarium and 1% by Scedosporium. Three patients died before starting any antifungal. Fifty-two received echinocandins (49 caspofungin and 3 anidulafungin), 22 liposomal amphotericin B (L-AmB), 15 azoles (7 fluconazole, 3 posaconazole, 3 voriconazole and 2 itraconazole) and 8 pts combo therapy (5 posa+L-AmB, 2 Caspo+L-AmB, 1 vori+caspo). Thirty-eight pts died within 30 days from FBSI diagnosis, 28 (74%) of whom due to infection. Among these 12 (43%) suffered from AML (1 in induction, 1 in CR, 10 had refractory/relapsed disease), 2 (7.2%) from ALL (all with refractory/relapsed disease), 7 (25%) from NHL (2 in induction, 2 in CR, 3 with refractory/relapsed disease), 4 (14%) from refractory/relapsed MM, 1 (3.6%) from MDS in remission, 2 (7.2%) from newly diagnosed MDS/MPN. In 8 pts (21%) for whom we cannot discriminate if death was subsequent to FBSI only or to uncontrolled HMs, fungal isolates were all rare yeast or molds except 2. Mortality was related only with advanced phase of underlying HM (p Conclusions: Nowadays FBSI represents a rare complication of HMs, as a consequence of wider availability of effective antifungal prophylaxis. Candidemia still represents the most important cause of FBSI, although about 25% of FBSI are due to rare yeast or molds. Regardless a lowering incidence, the observed mortality remains high even with target treatment. Disclosures No relevant conflicts of interest to declare.

[Graphic][1] Introduction. Multiresistant (MR) bacteria colonization is considered predictive of related bloodstream infections (BSI), which are worrisome among hematological patients (pts). Few data are available about the actual incidence of MR colonization and the probability of developing a BSI in this population. A multicentric prospective observational study has been carried out within the SEIFEM group, with the aim of detecting the incidence of MR bacterial colonization and the probability of developing MR BSI in hematological pts. Patients and Methods. Between March 1st and August 31st 2015, all pts with a hematological neoplasm admitted to 18 Italian Centres participating to SEIFEM were screened for MR colonization with a rectal swab; cultures of other sites were performed if clinically indicated. Patients showing MR bacterial colonization were recorded in a database where the occurrence of any BSI was correlated with age, gender, type and phase of disease, stem cell transplantation (SCT), presence of invasive devices, type of colonizing bacteria. Results. During a 6-month period, 189 pts with MR colonization were observed. Incidence was 8.9% among all admissions (189/2122). Median age was 59y (range 0-89) and M/F ratio 116/73. Eighty-two pts were affected by acute leukemia, 75 by lymphoma, 24 by myeloma, 6 by chronic myeloproliferative/myelodysplastic syndromes and 2 by aplastic anemia. Forty-four pts underwent SCT (28 autologous and 16 allogeneic). Vancomycin resistant enterococci (VRE) were responsible for colonization in 15 (7.9%) pts, extended spectrum beta-lactamases producing (ESBL-P) enterobacteria in 80 (42.3%) and carbapenemase producing (CP) Gram-Negative Rods (GNR) in 108 (57.1%). Thirteen of 14 pts with multiple colonizations had both ESBL and carbapenemase producing enterobacteria. Multivariate analysis of risk factors for type of MDR colonization showed that a complete hematologic remission was associated to ESBL-P enterobacteria colonization, but protective for CP strains (OR 2, 1.1-3.7, p=0.02 and 0.43, 0.23-0.79, p=0.006, respectively). Overall, 62 pts (32.8%) colonized with MR bacteria developed at least one BSI during the period of observation; 36 of them (58.1%; 19% of the whole series) developed BSI by the same pathogen (MRrel-BSI) (2 VRE, 14 ESBL-P E. coli , 2 ESBL-P K.pneumoniae , 1 ESBL-P E. aerogenes , 12 CP K. pneumoniae , 3 CP P. aeruginosa and 2 CP Acinetobacter spp). The rate of MRrel-BSI according to antibiotic resistance was 13.3% for VRE colonization, 19.5% for ESBL-P enterobacteria and 17.6% for CP GNR. CP K. pneumoniae , but not other CP enterobacteria, was predictive of MRrel-BSI (26.7%). In 82% of cases, MRrel-BSI occurred during neutropenia. At multivariate analysis of predictors of BSI, a relapsed/refractory hematological disease was associated to MRrel-BSI (OR 3.1, 1.4-6.7, p=0.005). Unrelated BSI were also observed in 32 pts (51.6%; 16.9% of the whole series), including 6 MR BSI (2 CP P. aeruginosa , 3 CP K. pneumoniae and 1 VRE). After a median follow-up of 80 days (range 0-270), 25 pts died (13.2%). Three-month overall survival (OS) of the entire cohort was 86%±2.9SE, being significantly lower for pts colonized with VRE (71%) and CP (82%) in comparison with those colonized with ESBL-P bacteria (97%, p=0.0018 and 0.0043 respectively) (Fig.1). Death was attributable to CP GNR related BSI in 5 pts and to VRE related BSI in 1. Multivariate analysis showed that CP GNR related BSI (OR 8.3, 2.2-30.5, p=0.001) and VRE related BSI (OR 87.9, 1.1-675.9, p=0.04), together with intensive care unit admission (OR 50.6, 4.5-570.9, p=0.001) were independent predictors of mortality at 30-days from known colonization, whereas having disease in complete remission was protective (OR 0.02, 0.001-0.43, p=0.01). Conclusions. Incidence of MR colonizing bacteria, particularly ESBL-P and CP GNR, affects nearly 10% of italian hematological cancer pts and results in a MRrel BSI in about one fifth of cases, mainly during neutropenia. MRrel-BSI are responsible for more than 50% of BSI observed in MR colonized pts and are significantly more frequent in relapsed/refractory hematologic disease. VRE and CP GNR colonizations but not ESBL-P are associated to lower OS and predict for a higher fatality of related BSI. Among CP enterobacteria, only K. pneumoniae is associated with MRrel-BSI. Empiric antibiotic treatment should be better tailored taking into account these results. ![Figure 1][2] Figure 1 Disclosures No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif [2]: pending:yes

OBJECTIVES Aim of this prospective study was to evaluate the risk of invasive fungal infection (IFI) in patients (pts) with acute promyelocytic leukemia (APL) and to compare APL pts with patients affected by non promyelocytic acute myeloid leukemia (npAML) in order to evaluate factors potentially linked to IFI in these two subsets of acute myeloid leukemia. PATIENTS AND METHODS From January 2010 to April 2012 all pts with newly diagnosed AML were registered in 33 Italian participating centers. A minimum follow up of 90 days after 1st induction chemotherapy was requested for all pts. A prolonged follow up until June 2014 was made only for APL. Data were collected about age, gender, AML subtype, treatment and also about post chemotherapy risk factors for IFI (duration of neutropenia, mucosal damages, vomiting, diarrhea, presence of medical devices), antifungal prophylaxis, onset of IFI, level of certainty (possible/probable/proven), and antifungal treatment. Only for APL the survey was prolonged for at least 3 months in order to analyze if these pts have an IFI risk during other than first induction phases. RESULTS 1,192 consecutive newly diagnosed adult AML pts (npAML:1,086/APL:106) were enrolled in the study. Among npAML pts, those receiving low dose chemotherapy and/or palliative treatment were excluded from the analysis; in the remaining 881 pts 214 cases (24%) of IFI were recorded. Considering APL, 3 pts were excluded from the analysis due to early death (1 pt) or bad performance status (2 pts). The remaining 103 pts received APL treatment according to local protocols: all trans retinoic acid (ATRA) plus chemotherapy (90 pts) or ATRA plus arsenic trioxide (ATO)(13 pts). Only 8 (8%) APL pts developed an IFI after the induction phase: 1 proven, 3 probable and 4 possible IFI. All cases were caused by molds. All APL were followed for a median follow up of 36 months (range 3-54). During this time only 2 other cases of IFI were observed: 1 possible IFI during consolidation at 16 weeks from APL diagnosis and 1 probable aspergillosis in a rare case of APL relapse at 132 weeks from APL diagnosis. All the IFI occurred in pts treated with ATRA plus chemotherapy. IFI was fatal in only 1 case (cerebral aspergillosis), all the other pts recovered after antifungal treatment. A comparison between npAML and APL was made in order to analyze the risk of IFI within 90 days after induction treatment among these 2 groups of patients (see table). A significantly lower number of overall IFI and systemic antifungal treatment was observed in the APL group, in spite of the fact that systemic anti mold prophylaxis was significantly less frequently utilized. | | || | | APL | npAML | p | | Number of pts | 103 | 881 | | | Mean age | 51 | 55 | 0.01 | | m/f | 50/53 | 448/433 | N.S. | | Performance status (WHO) 0-1 >1 | . 76 27 | . 284 597 | .

Abstract 3747 Poster Board III-683 Background despite the prognosis of aggressive non-Hodgkin Lymphoma has considerably improved over the past decades, the treatment of elderly patients with NHL is still a difficult challenge for the clinician. A retrospective EORTC study conducted in patients with aggressive NHL and age above 70 years showed that about half of patients received an aggressive treatment and that only 15% of investigators employed full-dose regimens from the first cycle. We here present the preliminary data of CHOP-like regimen delivered as first-line or salvage therapy to elderly or young patients with NHL and not eligible for more aggressive therapy. Patients and methods from July 2006 to January 2009, 27 pts (M/F:11/16) with a median age of 71 years (range: 53-84) were included in the study. Twenty-four pts (88%) were more than 65 yo, 18 (66%) had high-grade and 9 (34%) an indolent lymphoma. Stage III-IV disease according to Ann Arbor staging occurred in 18 pts (66%) whereas aaIPI, evaluated only for pts with aggressive NHL, was 3 2 in 9 pts (18%). ENS involvement ≥ 1 was present in 11 (41%) and BM involvement in 13 pts (48%). Most of pts (60%) had ECOG PS ≥ 1. Twenty out of 27 pts (74%) received COMP±R as first-line treatment and 7 (26%) as salvage therapy; all but one of pre-treated pts had received more than 1 line of chemotherapy (range 2-4). Twenty-five (92%) pts had co-morbidity with more than 1 disease in 44% of cases. Median LVEF was 59% (range: 35-80%). COMP±R regimen consisted of cyclophosphamide 750 mg/m2 IV d1, vincristine 1.4 mg/m2 IV d1 (capped at 2mg), liposome-encapsulated doxorubicin (MyocetÒ) at the dose of 50 mg/m2 IV d1 and Prednisone 100 mg/die PO d 1-5 with or without Rituximab at dose of 375 mg/m2 d8 at first course and at d1 of subsequent courses according to B or T-cell lymphoma phenotype respectively. To pts with early stage disease were planned 4 courses of COMP±R±IF-RT while those with advanced stage of disease received six courses of chemotherapy delivered every 3 weeks. Median number of cycles delivered was 5.6 (range: 4-8). All patients completed the planned treatment and most of them (92%) received G-CSF at dose of 300 mg/die as primary (67%) or secondary (25%) prophylaxis. ESA support was need in 8 pts (30%). Results complete response (CR) was achieved in 21 (78%) and partial response (PR) in 3 (11%) of pts with an ORR of 89%; three pts had stable (n=2) or progressive disease (n=1). The regimen was safe and well tolerated with dose reduction occurring in 9 pts (34%). None of pts developed cardiac toxicity. The mainly adverse events recorded was neutropenia occurring in 15% of pts and febrile neutropenia in 6 pts (23%). Extra-haematological toxicity was mild (WHO grade 1-2) and recorded in 18% of pts. There was no treatment-related fatal toxicity. With a median follow-up of 15 months (range 6-33) the OS and EFS was 93% and 89% respectively. Conclusion COMP±R regimen shows to be safe and effective in a group of elderly patients both as first line or salvage therapy. However more patients and longer follow-up is required to assess definitively the role of this regimen in elderly patients with untreated aggressive NHL. A prospective phase II trial is ongoing at our Institution. Disclosures: No relevant conflicts of interest to declare.