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Lymphomas presenting and mimicking soft-tissue masses are important to recognize, to avoid unnecessary treatment delays or extensive surgery. We describe a case of primary anaplastic large cell lymphoma (ALCL) arising from a deep skeletal muscle in a middle-aged male. He presented with a two-month history of swelling of his right thigh and mild fever, which led to a diagnosis of abscess formation. Antibiotics were prescribed for two weeks, with little improvement of symptoms. Subsequently, an exploratory surgery, with excision of the mass, demonstrated a ALCL of the psoas muscle, ALK-1 positive.

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.

INTRODUCTION Small-sized pigmented lesions (SSPL)

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

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050 ). RESULTS We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

Background. Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. CMM pathogenesis involves genetic and environmental factors. Recent studies have led to the identification of new genes involved in CMM susceptibility: beyond CDKN2A and CDK4, BAP1, POT1, and MITF were recently identified as potential high-risk melanoma susceptibility genes. Objective: This study is aimed to evaluate the genetic predisposition to CMM in patients from central Italy. Methods: From 1998 to 2017, genetic testing was performed in 888 cases with multiple primary melanoma and/or familial melanoma. Genetic analyses included the sequencing CDKN2A, CDK4, BAP1, POT1, and MITF in 202 cases, and of only CDKN2A and CDK4 codon 24 in 686 patients. By the evaluation of the personal and familial history, patients were divided in two clinical categories: “low significance” and “high significance” cases. Results: 128 patients (72% belonging to the “high significance” category, 28% belonging to the “low significance” category) were found to carry a DNA change defined as pathogenic, likely pathogenic, variant of unknown significance (VUS)-favoring pathogenic or VUS. Conclusions: It is important to verify the genetic predisposition in CMM patients for an early diagnosis of further melanomas and/or other tumors associated with the characterized genotype.

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.

Background Phthalates, potential endocrine disruptors added to plastics, are found in numerous products and contaminate many environmental matrices, resulting in a widespread human exposure virtually interfering with fetal and neonatal development. This study aims to evaluate, by repeated mothers and children urine monitoring, the exposure to phthalates in newborns and to investigate its potential effects in early life. Methods A cohort study, recruiting mothers and newborns at an Italian hospital, is ongoing. Prenatal exposure is assessed by measuring 6 phthalates in maternal and neonatal urine; while postnatal exposure is assessed in the infants urines at 3rd and 6th month. Infants undergo periodic visits (t0, t3, t6, t12, t24) to assess growth, neurocognitive development and urinary sex hormone levels; mothers fill in exposure questionnaires at t0 and t6. Results To date, 148 mother-child couples have been enrolled, 74 children checked at t3 and 35 at t6. The newborns (3.4±0.3kg weight, 50.2±1.7cm length), show physiological hormonal levels: LH 0.6±1.8mIU/ml; FSH 1.5±1.6mIU/ml, testosterone 10.3±4.8ng/ml, estradiol 843.9±972.4pg/ml. Phthalates appear highly widespread both in mothers and infants, although at low levels. MEP shows the highest levels (mothers: 37.3±83.2µg/L; infants: 19.6±32.8µg/L), followed by MnBP (mothers: 11.3±14.4µg/L; infants: 21.3±25.5µg/L) and MBzP (mothers: 3.9±3.9µg/L; infants: 8.1±9.8µg/L). All mothers report frequent contact with products potentially containing phthalates, however mother-child couples levels showed very low correlations. Conclusions Exposure to phthalates for infants appears widespread, albeit at low levels. Neonatal urine biomonitoring is a valid tool to evaluate child exposure, able to produce more accurate information than maternal urine. Key messages Biomonitoring of childhood urine produces accurate data on pre and postnatal exposure to phthalates. Biomonitoring of childhood urinary phthalates can enhance the assessment of their potential effects on growth and development.

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous stem cell transplantation. Overall, 19% of patients received ibrutinib during the course of the disease. According to IPSSWM, 63% were classified as low risk, 27% as intermediate risk and 10% as high risk. Five-year OS was shorter in high-risk as compared with low or intermediate risk patients (92.9% vs 100% P = .002). According to revised IPSSWM, 92% were classified as very low or low risk and 8% as intermediate risk, with a shorter 5-year OS in the latter group (87.5% vs 100%, P = .028). The OS of young WM patients was not significantly reduced as compared with age-matched, sex-matched and calendar year-matched general population. Early diagnosis, absence of high-risk features in symptomatic patients and high efficacy of modern treatments are the main determinants of the excellent outcome of young WM patients.

Introduction Non-pegylated liposomal doxorubicin (NPLD) is considered a good alternative to conventional doxorubicin for the treatment of older patients (pts) with aggressive lymphomas and/or at high risk for cardiological toxicity. The use of R-COMP for the treatment of older pts with DLBCL has been supported by several small retrospective studies . In this report we describe the characteristics and outcomes of pts who were prospectively enrolled in the Elderly Project (EP) and who were treated with R-COMP and compared them with pts treated with conventional R-CHOP. Methods. This analysis was conducted starting from the dataset of the EP study. The use of NPLD was allowed according to 648/96 law, treatment decision was left to physician discretion and was independent of frailty status. For the purposes of this analysis, we included all pts who were treated with full doses of R-CHOP and R-COMP. The study endpoint were progression free survival (PFS) and overall survival (OS). A propensity score analysis was conducted to account for the main confounding factors. Results Overall 691 out of 1163 pts of the EP were treated with R-CHOP (383; 55%) or R-COMP (308; 45%); median age was 71 and 76 years for R-CHOP and R-COMP, respectively (p < 0.001) (Table 1). Pts were similarly distributed among different IPI groups for R-COMP or R-CHOP. Based on simplified Geriatric Assessment (sGA) 88%, 11% and Conclusions Data from the prospective observational EP study did not show significant differences in terms of efficacy comparing R-COMP to standard R-CHOP. The higher frequency of UNFIT and FRAIL pts among those treated with NPLD suggests R-COMP is a good strategy to offer a curative treatment to these groups of pts. Figure 1 Figure 1. Disclosures Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: 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; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cavallo: ROCHE: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Gilead: Speakers Bureau. Fabbri: Servier/Pfizer: Honoraria; Takeda: Other: Travel, Accomodations, Expenses; Takeda: Honoraria. Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Ferrero: Incyte: Membership on an entity's Board of Directors or advisory committees; Morphosys: Research Funding; Gilead: Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau; Takeda: Other: travel expenses, accommodation. Nassi: Takeda: Consultancy; Kyowa Kirin: Consultancy; Incyte: Consultancy; Roche: Consultancy. Musuraca: Janssen, Incyte, Roche: Consultancy; Janssen, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen, Roche, Incyte: Honoraria. Flenghi: Janssen: Other: Travel, Accomodations, Expenses; Roche: Other: Travel, Accomodations, Expenses. Marcheselli: sandoz: Membership on an entity's Board of Directors or advisory committees. Luminari: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Other: Travel, Accomodations, Expenses; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; GENELAB SRL: Consultancy.

Venetoclax is the first BCL-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia (CLL) alone or in combination with anti-CD20 monoclonal antibodies (MoAbs). Initial studies have shown high efficacy of venetoclax monotherapy or in combination with rituximab with an overall response rate of 79-92% in patients with relapsed/refractory (R/R) CLL. To investigate the use of venetoclax combinations in a real-world population, we designed this observational retrospective and prospective study aimed at defining the outcome of patients with R/R CLL treated with venetoclax-based regimens outside clinical trials in Italy. Efficacy (progression-free survival -PFS-, overall response rate -ORR-, complete response -CR-, measurable residual disease -MRD-) and safety (most frequent adverse events -AE-, grade 3-4 AE, laboratory and clinical tumor lysis syndrome -TLS-) data were collected within the study through a web-based platform after patients signed written informed consent. As of July 8 th, 2021 124 subjects (85 males, 39 females) were enrolled into the study (Table 1). Median age at venetoclax initiation was 70 years (44-91), median CIRS score 4 (0-14), median creatinine clearance 70 ml/min (22-123). A relevant proportion of patients presented adverse prognostic features, including TP53 aberrations [32% TP53 mutation and/or del(17p)], unmutated IGHV (77%). At the time of venetoclax initiation, patients had received a median of 2 previous therapies (1-8), with 57% previously exposed to BTK and/or PI3K inhibitors. 67/117 (57%) patients received venetoclax alone, while 50 were treated with a combination of venetoclax + rituximab (VenR), information on treatment plan was missing in 7 patients. Patients on venetoclax monotherapy compared to those receiving VenR showed a higher percentage of elevated LDH at baseline (64% vs 38%), were more heavily pretreated (median lines of therapy 3 vs 1), and had more frequently received treatment with ibrutinib (66% vs 27%) and/or idelalisib + rituximab (29% vs 4%). After a median follow-up of 13.7 months (0-41.9), the estimated 12m-PFS was 82% (CI 74-90%) (Figure 1), and the estimated 12m-overall survival (OS) was 83% (CI 76-91%). The best ORR in the whole cohort was 85% (CI 95% 76-91%) with a CR rate of 40%; best response was reached after a median of 3.9 months of treatment (range 0.6-30.5). The best ORR was not different in patients receiving VenR vs venetoclax alone (83% vs 88% respectively, p = n.s.), while the CR rate was significantly higher in those receiving VenR vs venetoclax alone (57% vs 30%, p=0.011). The ORR and CR rate in patients previously exposed to BTK and/or PI3K inhibitors were significantly lower (77% and 29% respectively), and the 12m-PFS was shorter in patients previously treated with ibrutinib compared to ibrutinib-naïve (75% vs 89%, p=0.005). Twenty subjects discontinued venetoclax (median time to discontinuation 4.1 months, range 0.4-10.8), 8 due to disease progression, 3 Richter's transformation, 7 AEs, 1 was lost to follow-up and 1 underwent planned allogeneic stem cell transplantation. Venetoclax-based regimens were well tolerated, with the most frequent AE of any grade related to venetoclax being neutropenia (79.6%), grade 3-4 in 61.9% (Table 2). In the whole cohort one grade 3 clinical TLS occurred and resolved without sequelae, and only 2/124 patients experienced laboratory TLS during ramp-up phase (both grade 1). No treatment-related death was reported. In conclusion, this analysis presents the results of one of the largest cohort of patients with R/R CLL treated with venetoclax-based regimens outside clinical trials and confirms the favourable efficacy and safety profile of the drug. In this patient population highly enriched for unfavorable disease features (1 out of 3 carrying TP53 aberrations, almost 80% with unmutated IGHV) venetoclax-based regimens were able to obtain a response in a high proportion of cases, with a very short time to best response (less than 4 months). As expected, response duration was shorter in patients previously exposed to BTKi/PI3Ki. When we compared the outcome of patients treated with venetoclax monotherapy vs VenR, the addition of anti-CD20 MoAb allowed to reach deeper responses by significantly increasing the CR rate. As the study and its data collection are still ongoing, the updated analysis of an expanded cohort with longer follow-up will be presented at the meeting. Figure 1 Figure 1. Disclosures Scarfo: Janssen: Honoraria, Other: Travel grants; Astra Zeneca: Honoraria; Abbvie: Honoraria. Quaglia: Roche: Other: Travel grants; Janssen: Honoraria, Other: Travel grants, Speakers Bureau; Sandoz: Consultancy; AstraZeneca: Honoraria. Marasca: AbbVie: Honoraria, Other: Travel grants; AstraZeneca: Honoraria; Janssen: Honoraria, Other: Travel grants. Sanna: Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Laurenti: Roche: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Honoraria; BeiGene: Honoraria. Gaidano: Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Honoraria, 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. Reda: Beigene: Consultancy; Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Molica: Astrazeneca: Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Sportoletti: AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria. Galimberti: AbbVie, Janssen: Honoraria, Other: Travel grants; Incyte: Speakers Bureau. Mauro: AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Cuneo: Janssen: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Ghia: AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; ArQule/MSD: Consultancy, Honoraria; Sunesis: Research Funding.

Background. The World Health Organization defines Waldenström Macroglobulinemia (WM) as a lymphoplasmacytic lymphoma associated with a serum immunoglobulin M (IgM) monoclonal protein. Since bone marrow (BM) infiltration is always present, while extramedullary involvement is infrequent, trephine BM biopsy is mandatory based on currently used diagnostic criteria, while multiparameter flow cytometry (MFC) studies are recommended to support the diagnosis (Owen et al, 2003). Next generation flow cytometry using panels with 8 to 17 monoclonal antibodies (MoAb), high number of cell acquisitions and appropriate software have shown an increased sensitivity, being able to detect one tumor cell among 10.000 normal cells (10-4) or even more. Aims of the study. Here we report an extensive phenotypic characterization by eight color MFC of a large prospective cohort of newly diagnosed WM patients, enrolled in the multicenter, observational trial BIO-WM (NCT03521596). In this study we evaluated the potential role of MFC on BM and peripheral blood (PB) samples as an alternative to BM biopsy in the diagnostic work-up of WM, with the final goal to assess the feasibility of a non-invasive or at least less invasive diagnostics. Methods. The diagnosis of WM was made using the criteria of the Second International Workshop on WM. Patients without bone marrow biopsy were excluded from the analysis. Whole BM and PB samples were processed following the bulk lysis protocol and stained using 8-color combination of the following fluorochrome-conjugated monoclonal antibodies: cIgM, CD56, CD5, CD19, CyK, CyL, CD38, CD45 (screening panel). CD5- lymphoproliferative disorders with two populations in different maturation stage showing identical cytoplasmatic light chain restriction underwent further characterization with six 8 color-panels (characterization panel). A minimum of 1x106/L cells per tube was acquired. The full list of monoclonal antibodies is reported in Table 1. Results. We analyzed 173 prospective patients with a histologic diagnosis of WM, either asymptomatic (n=46, 27%) or symptomatic (n=127, 73%). Their baseline characteristics are reported in Table 2. MFC results on BM samples collected at diagnosis were available in 165 patients. The median white blood cell (WBC) count was 13.5 x 109/L (IQR: 4.9-94) and the median number of cell acquisitions was 1.16 x 106 (IQR: 0.91-1.58). Clonal CD19+ B-cells were detected by MFC in 155/165 cases (94%) and showed k light chain restriction in 76% of cases. The median percentage of clonal CD19+ B-cells out of total BM WBC was 5.9% (IQR: 2.9-12.4). Twelve cases out of 165 (7%) were CD5+. The complete phenotype of clonal B CD19+ lymphocytes is shown in Figure 1. Clonal CD38+ plasma cells were detected in BM samples in 86% of cases and were CD20+ in 51% of cases. The median percentage of clonal CD38+ plasma cells out of total BM WBC was 0.18% (IQR: 0.05-0.47). The complete antigenic expression of clonal plasma cells is shown in Figure 2. The MYD88 (L265P) mutation was found with droplet digital polymerase chain reaction (dd-PCR) in 95% of patients with detectable clonal CD19+ B-cells in BM samples, without significant difference between CD5- and CD5+ cases (95% versus 93%, P=0.698). Paired BM and PB samples were available in 157 patients. Clonal CD19+ B-cells were detected in BM samples in 149/157 cases (95%) and in PB samples in 98/157 cases (58%). Overall, there was a slight agreement between BM and PB MFC results according to Landis and Koch scale (63%, k = 0.138). Conclusions. The comparison of MFC results on BM samples with BM histology in this large prospective cohort of WM patients suggests that eight-color MFC is highly sensitive and is able to identify the majority of patients with WM. Conversely, the comparison of MFC results on paired BM and PB samples indicates that MFC on PB samples has a low sensitivity, missing approximately 40% of cases. The integration of MFC results on BM samples with MYD88 mutation status assessed with a highly sensitive method such as dd-PCR may be considered as an alternative, less invasive method for the diagnosis of WM. Further analyses within this trial will assess the role of MFC combined with molecular profile of patients for the differential diagnosis between WM and other mature B-cell lymphoproliferative disorders as well as for the discrimination between WM and IgM monoclonal gammopathy of undetermined significance. Figure 1 Disclosures Varettoni: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: Travel/accommodations/expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses. Ferrero:Servier: Speakers Bureau; Gilead: Research Funding, Speakers Bureau; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Puig:JANSSEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; TAKEDA: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; AMGEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; THE BINDING SITE: Consultancy, Honoraria; BRISTOL-MYERS SQUIBB: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; CELGENE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau. Ferrari:Abbvie: Honoraria. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Marchetti:Takeda: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings; AbbVie: Other: Sponsored meetings; Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau. Re:BerGenBio ASA: Research Funding. Boccadoro:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding; AbbVie: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Garcia-Sanz:Novartis: Honoraria; Janssen: Honoraria, Research Funding; Incyte: Research Funding; Gilead: Honoraria, Research Funding; BMS: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria; Takeda: Consultancy, Research Funding.

BACKGROUND: Cutaneous involvement in Hodgkin lymphoma (HL) is a rare finding. Few cases have been reported in literature, most describing paraneoplastic manifestations. Only very few papers have described primary HL skin infiltration, reporting a wide range of clinical presentations that frequently include ulcers; plaques, nodules and papules have also been noticed. CASE SUMMARY: We report the case of a 56-year-old man who presented fever, multiple adenomegalies of neck and axilla and thick serpiginous skin lesions involving bilateral pectoral regions. After an initial diagnostic workup for a suspected active infectious disease, a lymph node biopsy was performed, which showed a neoplastic invasion from a mixed cellularity classical HL. The same histological pattern was described in a cutaneous biopsy of the chest lesions. The other staging procedures performed revealed an advanced disease, with unfavourable clinical prognostic features. The patient was prescribed 6 cycles of ABVD chemotherapy scheme (doxorubicin, bleomycin, vinblastine, dacarbazine), a regiment that requires demonstration of metabolic response achievement at the interim PET/CT scan to confirm continuation or to change therapeutic strategy. CONCLUSION: Skin involvement in HL is a rare finding and may represent a challenging clinical presentation due to extremely various types of lesions observed.

International audience; Background: International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported.Subjects, materials, and methods: We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ConC]: n = 9) or subsequently (sequential cohort [SeqC]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like).Results: Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC. At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%).Conclusion: Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity.Implications for practice: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.

not available

Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non–Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients.

Background and objectives Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes. Methods We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin’s lymphoma, and mantle cell lymphoma. Results Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin’s lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients. Conclusions The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes.

Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post-transformation outcome of 176 biopsy-proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five-year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5-year progression-free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre-transformation treatment lines and a short time-to-transformation.

Background Actinic keratosis (AK) is a photo-induced skin lesion. It has been considered by several authors as in-situ squamous cell carcinoma (SCC), that can evolve to invasive SCC (iSCC). Given the malignant potential and because it is impossible predict which AK will evolve in iSCC, it is necessary to treat each lesion. Multiple therapeutic approaches have been described to treat AKs. In addition to the topical drugs, photodynamic therapy (PDT) has become an established therapeutic modality for grade I and II of AKs of face and scalp. Recently the daylight photo-dynamic therapy (DL-PDT) has found extensive use in the care of the AK and in the field cancerization. Methods The study included 101 patients, 90 males and 11 females, mean age 71, phototype I-II, with multiple AK I and II of the face and the scalp, treated with DL-PDT. Patients were clinically evaluated for 3 months. The aim of this study was to show our experience in Daylight Photodynamic Therapy, to confirm the validity in term of efficacy and safety of DL-PDT for I and II AK of face and scalp and to underline the patient's higher satisfaction for this type of treatment and his availability to be retreated with the DL-PDT. Results The efficacy was complete in 16 patients (15.8%), in 71 patients (70.3%) was much improved or improved and only in 14 (13.9%) subjects were minimal, while nobody had worsened or changed. The majority of patients (84.2%) patients were satisfied of the efficacy as well of the cosmetic results, only 15 (14.9%) were low satisfied and one patient was not satisfied. Conclusions This study confirms that the DL-PDT is a good alternative to c-PDT for the treatment of grade I and II AK of the face and scalp and in Rome, as in Southern Europe, it is possible to perform the DL-PDT in almost every month of year.

The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76 years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.

Plasmablastic lymphoma (PBL) is an uncommon, aggressive B-cell lymphoma mostly occurring in the oral cavity of human immunodeficiency virus (HIV) positive patients, but also described in extraoral sites and in HIV negative patients. One of the relatively common extraoral sites of PBL is the gastrointestinal (GI) tract. Few cases of PBL have been reported in association with inflammatory bowel disease (IBD). Here, we describe the unique presentation of a PBL involving the large bowel superficially along its entire length and without forming a tumor mass in an HIV negative patient with a recent diagnosis of ulcerative colitis.

In this past decade, new therapeutic approaches based on the use of rituximab, high-dose cytosine-arabinoside, and autologous stem cell transplantation (ASCT) have changed the paradigm of mantle cell lymphoma (MCL) treatment, significantly improving the quality and duration of response and

Background/Objectives The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions. Methods This is a retrospective case-series study that analysed the dermoscopic features of 582 pigmented facial lesions. Results The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut-off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7. Conclusion The optimal cut-off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions.

Background. Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma typical of the elderly population, with a median age at diagnosis of 65-70 years and median overall survival of approximately 10 years. Age is the most important prognostic factor in WM, and unrelated mortality significantly impacts survival in elderly patients. The past two decades have witnessed important treatment advances in WM, with the introduction of anti-CD20 monoclonal antibodies in the early 2000s and of ibrutinib in more recent years. Less than 10% of WM patients are diagnosed at young age, and few studies have addressed their characteristics and outcome in the era of immunotherapy and targeted therapies. Here we report the presenting features, treatment and outcome of WM patients younger than 55 years diagnosed in 12 Hematologic Centers across Italy between 2000 and 2018. Patients and Methods. Diagnostic criteria were those established during the second International Workshop on WM (Owen et al, 2003) and were retrospectively applied to patients diagnosed before 2003. The overall survival (OS) observed in the study cohort was compared with the expected survival of the general Italian population matched by sex, age and calendar year. The expected survival estimates were derived from Italian life tables (Istituto Nazionale di Statistica, ISTAT). Results. The median age of patients included in the study was 50 years (interquartile range, IQR: 46-52). Their clinical characteristics at diagnosis are reported in Table 1. With a median follow-up of 5.6 years (IQR 3.1-9.1), 76 of 129 patients (59%) have been treated, at diagnosis (n=31, 41%) or after initial observation (n=45, 59%). The median treatment-free survival was 39 months. According to ISS-WM prognostic score, 58% were classified as low risk, 30% as intermediate risk and 12% as high risk. Frontline therapy included Rituximab in 71/76 patients (93%). Rituximab was associated with chemotherapy in 62 patients (82%), whereas 9 patients (12%) received a chemo-free induction. Five patients (7%) received chemotherapy only as first-line therapy (Table 2). The overall response rate (ORR) to induction therapy was 85%, including 39% CR+VGPR. Two patients received Rituximab maintenance for 2 years. The median progression-free survival (PFS) after first-line therapy was 76 months. Four of 76 patients (5%) received an autologous stem cell transplantation at relapse/progression. Overall, 14/76 patients (18%) received ibrutinib as first (n=2) or as subsequent line of therapy (n=12). During follow-up, 4/76 patients (5%) developed a solid cancer (bladder n=2, breast n=1, prostate n=1) and 2 a second hematologic cancer (chronic myelomonocytic leukemia n=1, secondary MDS n=1). Using a competing-risk model, accounting for death from any cause as the competing event, the cumulative incidence of second cancers was 2% at 5 years and 5.8% at 10 years. Three patients have died, 2 due to WM and 1 due to acute myeloid leukemia. The 5-and 10-year OS from diagnosis were 99% and 96% respectively. In a time-dependent survival analysis, considering therapy as a time-dependent covariate, the OS of treated and untreated WM patients was not significantly different (P = 0.162) (Figure 1). Among treated patients, the OS was significantly shorter in high-risk patients as compared with low- and intermediate-risk patients (5-year OS 85.7% versus 100%, P=0.018) (Figure 2). The OS of young WM patients was not significantly reduced as compared with age-, sex- and calendar year- matched general population (P > 0.05) (Figure 3). Conclusions. The presenting features of young WM patients resemble those typically described in the elderly WM population. Among treated patients, more than half are low-risk according to ISS-WM, confirming age as the most important prognostic factor. More than 90% of patients received Rituximab as part of the upfront treatment, mainly in combination with chemotherapy. Ibrutinib seems to be preferred over autologous stem cell transplantation in the relapsed/refractory setting. The outcome of young WM patients treated in Italy in the contemporary era was excellent in terms of both PFS and OS, with a life expectancy not significantly reduced as compared with the general population. Figure 1 Disclosures Varettoni: Gilead: Other: travel expenses; Janssen: Consultancy; Roche: Consultancy; ABBVIE: Other: travel expenses. Tedeschi:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen spa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SUNESIS: 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; Gilead: Consultancy. Benevolo:Novartis Pharmaceuticals: Consultancy. Del Fabro:Janssen: Consultancy. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Arcaini:Gilead Sciences: Research Funding; Celgene: Speakers Bureau; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy.

In 2003 the Fondazione Italiana Linfomi (FIL) started a clinical research program for investigating initial treatment of frail elderly patients with diffuse large B-cell lymphoma (DLBCL) identified by Comprehensive Geriatric Assessment (CGA). From 2003 to 2006, 334 elderly patients underwent CGA assessment, and 99 patients were classified as frail. Frail patients had a median age of 78 years, stage III-IV disease in 62% and age-adjusted International Prognostic Index (aaIPI) of 2-3 in 53%. Treatment consisted of several different regimens according to physician discretion. After a median follow-up of 36 months, 5-year overall survival (OS) was 28%. In multivariate analysis, aaIPI 2-3 (p = 0.005) and the presence of respiratory comorbidity (p = 0.044) were the only factors that showed independent correlation with OS. Frail patients had a poorer outcome compared with fit patients also if they were treated with rituximab-containing combination chemotherapy (hazard ratio 2.37, 95% confidence interval 1.48-3.78; p < 0.001). CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL.

BACKGROUND: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article.METHODS: For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01011920.FINDINGS: Between Feb 19, 2010, and Aug 27, 2014, 227 eligible patients were recruited. 219 of these 227 enrolled patients were assessable. At median follow-up of 30 months (IQR 22-38), patients treated with rituximab and thiotepa had a complete remission rate of 49% (95% CI 38-60), compared with 23% (14-31) of those treated with methotrexate-cytarabine alone (hazard ratio 0·46, 95% CI 0·28-0·74) and 30% (21-42) of those treated with methotrexate-cytarabine plus rituximab (0·61, 0·40-0·94). Grade 4 haematological toxicity was more frequent in patients treated with methotrexate-cytarabine plus rituximab and thiotepa, but infective complications were similar in the three groups. The most common grade 3-4 adverse events in all three groups were neutropenia, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity.INTERPRETATION: With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials.FUNDING: Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation.

Purpose The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. Patients and Methods Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). Results The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). Conclusion With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma in western countries. Overall, 70% of patients achieve complete remission after first treatment.[1][1] However, it is characterized by a pattern of relapsing and remitting disease. The outcome of patients with FL has clearly

We present the final results of a Phase II study that evaluated safety and efficacy of lenalidomide in combination with rituximab in 39 patients with recurrent small lymphocytic lymphoma (N=18), marginal zone lymphoma (N=8), or lymphoplasmacytic lymphoma (N=13). Patients received oral doses of lenalidomide 20 mg once daily on days 1-21 and rituximab 375 mg/m2 on day 14 of each 28-day course. Patients received up to 6 courses. The overall response was 54%, with a complete response of 21%. At 2 years, progression free survival, duration of remission, and overall survival were 45%, 76%, and 78%, respectively. The evaluation of treatment response by histology showed an overall response rates of 75%, 46%, and 50%, in marginal zone, lymphoplasmacytic and small lymphocytic lymphoma, respectively. Histology-based estimates of remission durations at 2 years were 100%, 100%, and 51% for marginal zone, lymphoplasmacytic, and small lymphocytic lymphomas, respectively. A log rank test showed that the marginal zone and lymphoplasmacytic lymphoma curves were marginally significantly different from the small lymphocytic lymphoma curve. Our results demonstrated that patients with recurrent marginal zone and lymphoplasmacytic lymphomas that responded to the combination treatment had long-lasting responses. Of note, no other studies have published the effects of this combination treatment on patients with relapsed lymphoplasmacytic lymphoma. Our findings showed a mild, predictable, and manageable toxicity profile. Confirmation of these results in Phase III trials will facilitate moving towards a chemotherapy-free approach in the management of indolent non-Hodgkin lymphoma. ClinicalTrials.gov; Identifier: [NCT01830478][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01830478&atom=%2Fhaematol%2Fearly%2F2016%2F02%2F01%2Fhaematol.2015.139329.atom

Acute promyelocytic leukaemia (APL) is a unique clinicobiologic entity that can be successfully treated with All-trans Retinoic Acid ATRA-based regimens. Some cases of acute myeloid leukaemia (AML) with nucleophosmin (NPM) mutations have an immunophenotype that is similar to APL. The objective of the study is to compare antigenic expression in a group of APL patients with that in AML patients with NPM mutations and an APL-like immunophenotype (CD15- CD34- HLA-DR-). A consecutive series of 40 APL and 12 NPM patients with an APL-like phenotype were included in the study. Immunophenotypic patterns were investigated by multiparametric flow cytometry. Promyelocytic leukaemia-retinoic acid receptor-α transcript type, NPM and FLT3 mutations were investigated using conventional methods. Statistically significant differences were found between APL and NPM-mutated AML in CD33, CD13, CD2 and CD110 reactivity. CD2 expression was absent in every patient with NPM-mutated AML. In addition, mean fluorescence intensity and the coefficient of variation (cv) of CD33 and CD13 showed statistical differences between the two groups for CD33 (p = 0.007) and a trend to significance for CD13 (p = 0.05). Furthermore, among 45 evaluable patients, CD110 expression statistically differentiates between the two groups: [2/33 (6%) in the APL group and 8/12 (66.6%) in the NPM-mutated AML (p = 0.014)]. However, these traits were subtle, raising the possibility of practical diagnostic challenges. In conclusion, CD110 and CD33 reactivity may be useful to distinguish APL from NPM-mutated AML with CD15, CD34 and HLA-DR negativity. Nevertheless, cytogenetic and molecular characterization is necessary to establish the accurate diagnosis of AML.

In this paper the numerical simulation of a free surface flow over a sharp-crested weir is presented. Since in this case the usual shallow water assumptions are not satisfied, we propose to solve the problem using the full weakly compressible Navier–Stokes equations with the Tait equation of state for water. The numerical method used consists of the new meshless Smooth Particle Hydrodynamics (SPH) formulation proposed by Ferrari et al. (2009) [8] , that accurately tracks the free surface profile and provides monotone pressure fields. Thus, the unsteady evolution of the complex moving material interface (free surface) can been properly solved. The simulations involving about half a million of fluid particles have been run in parallel on two of the most powerful High Performance Computing (HPC) facilities in Europe. The validation of the results has been carried out analysing the pressure field and comparing the free surface profiles obtained with the SPH scheme with experimental measurements available in literature [18] . A very good quantitative agreement has been obtained.

Background: Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-γ release blood assays T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy for latent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown. Methods and results: Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneously performed, their results were compared, and intertest agreement was evaluated. Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p < 0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (κ = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (κ = 0.16) or QFT-IT (κ = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001). Conclusions: Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based on these results, we recommend tailoring application of the new blood IFN-γ assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.

Eccrine poroma can mimic benign and malignant melanocytic and non-melanocytic lesions. To date, little is known about the dermoscopic features of this condition. Seven histopathologically proven cases of eccrine poroma were examined using dermoscopy by three independent dermatologists. Both glomerular and hairpin vessels were observed in 71% of cases, whereas linear irregular vessels were observed in 43% of cases. A white-to-pink halo surrounding the vessels and multiple pink-white structureless areas were also frequently found (in 86% and 71% of cases, respectively). Three dermoscopic "profiles" were identified, all characterized by the presence of a white-to-pink halo surrounding the vessels, as well as by the association of two additional different features, namely: glomerular vessels and pink-white structureless areas, glomerular and linear irregular vessels, hairpin vessels and linear irregular vessels. However, due to the small number of lesions studied so far, we suggest that these profiles should be considered as likely, but not definitely pathognomonic signs of eccrine poroma.

Despite its low incidence, vulvar melanoma carries a poor prognosis and shows a high tendency to metastasize because the diagnosis is often delayed. Although it is very well known that ultraviolet radiation is an important aetiological factor for cutaneous melanomas in adults, this cannot be considered true for vulvar melanoma. Chronic inflammatory disease, viral infections, irritant agents are the main factors suspected to induce mucosal melanoma. We report 10 cases of vulvar malignant melanoma observed in our institute from 1990 to 2005 and a review of the literature.

Background Recently, we identified and described dermoscopic aspects, present with a higher frequency in congenital melanocytic lesions with respect to acquired naevi. We also classified small- and medium-sized congenital naevi (CN) into nine subtypes according to their macroscopic and dermoscopic aspects.Objectives Because the recognition of dermoscopic features may be instrument dependent, in this study, we wanted to check whether dermoscopic patterns specific for CN can be identified in digital images acquired by means of different instruments. We also wanted to check the validity of our previously proposed classification and assess possible age- and site-dependent variations of dermoscopic patterns and naevus subtypes.Patients/methods Images corresponding to 384 small- or medium-sized CN were collected in eight different centres employing four different instruments. Lesion images were evaluated and checked for the presence of specific dermoscopic criteria, classified, and compared with a database of 350 acquired naevi.Results Specific and unspecific dermoscopic features were identifiable in images acquired by means of all four instrument types. The mean number of identified features per lesion did not vary according to the instrument employed for the acquisition of the images; however, it was lower for lesions recorded employing low magnifications. The previously proposed classification was easily applied to the whole image database. The variegated naevus type was identified as a highly specific clinical/dermoscopic pattern. Dermoscopic features varied according to age and location. The globular type prevailed in subjects under 11 years of age and on the trunk, whereas the majority of reticular lesions were located on the limbs.Conclusions Because definite clinical and histological criteria for the diagnosis of the congenital nature of naevi are lacking, the use of dermoscopy can be of great help in identifying those lesions where the presence of specific dermoscopic features makes the diagnosis of CN more likely. Moreover, dermoscopy can be useful both for the classification of lesions already identified as congenital according to definite clinical and anamnestic data and for a possible correlation of naevus phenotype and dermoscopic patterns to the risk of developing a malignant melanoma in prospective studies.