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The immune dysregulation during SARS-CoV-2 has the potential to worsen immune homeostasis after recovery. Patients with hematological malignancies with COVID-19 have changes both in the innate and adaptive immune responses. Little is known about the severity of immune dysfunction following recovery from COVID-19 in hematological patients.Here, we performed a comprehensive analysis of the lymphocyte subsets in peripheral blood mononuclear cells by FACS Canto II in 55 patients, including 42 with hematological malignancies 4-6 weeks after COVID-19.Hematological COVID-19 convalescents had deep reduction in CD3+ T cells, including helper T cells (CD3 + CD4+), naïve helper T cells (CD3 + CD4 + CD45RA+), and memory CD4+ T cells among with extremely low levels of Treg cells and decreased expression of both TCRα/β and TCRγ/δ. Severe immune dysregulation in hematological convalescents was expressed by increased activation of T lymphocytes, both as elevated levels of activated T cells (CD3 + HLA-DR+) and activated cytotoxic T cells (CD3 + CD8 + HLA-DR+).Our findings showed a profound impairment of the adaptive immune response in hematological convalescents which might be a result of persistent activation of T cells. Convalescents with lymphoid malignancies showed more pronounced depletion of key T lymphocytes subpopulations in creating an effective adaptive response and immune memory.

The use of novel small molecule inhibitors alone or in combination with anti-CD20 monoclonal antibodies for chronic lymphocytic leukemia (CLL) has raised a number of questions on efficacy, tolerability, long-term treatment adherence in patients with heterogeneous clinical features. To fill this gap, we designed a study focusing on treatment sequencing in patients with CLL in order to (i) compare the outcome of patients treated with chemoimmunotherapy (CIT) combinations in first-line versus those receiving Bruton's tyrosine kinase inhibitors (BTKi); (ii) characterize the efficacy and tolerability of venetoclax-based regimens; (ii) understand the impact of treatment sequencing when it comes to chemo-free options including venetoclax after BTKi and vice versa. Data from consecutive sets of patients diagnosed with CLL between 2000-2020 attended at 77 institutions affiliated with ERIC were collected and analyzed. Collected variables included: demographics, clinical stage at diagnosis, IGHV gene somatic hypermutation status; cytogenetic status for chromosomes 11q, 13q 17p and 12 determined by fluorescence in situ hybridization; TP53 gene mutation status; treatment; treatment response; discontinuation; reason for discontinuation; death. We included 9173 patients with a diagnosis of CLL who received at least one line of treatment. The median age at diagnosis was 67 years with a male:female ratio of 1.9. The median follow-up was 78 months (IQR, 48-120 months). Regarding novel targeted agents, 1860/9173 (20.2%) patients had received at least one line of treatment with BTKi (ibrutinib, n=1788; acalabrutinib, n=72) over the disease course; 631/9173 (6.9%) with venetoclax; and, 447/9173 (4.9%) with the PI3K inhibitor idelalisib. Seventy-nine patients were treated with both BTKi and venetoclax (59 BTKi followed by BCL2i, 20 vice versa). At last follow-up, 5870/9173 patients (64.0%) were alive, 3229/9173 (35.2%) died and 74/9173 (0.8%) were lost to follow-up. Patients treated with BTKi in first-line were enriched for TP53 aberrations [del(17p) 27.6%, TP53 mutation 26.3%] and unmutated IGHV genes (69%) and obtained an ORR of 87.7%. Of these, 136 (26.3%) discontinued treatment after a median of 1.2 years (0.07-5.98); main reasons of discontinuation were toxicity (40.5%) and failure (26.2%). Among 631 patients treated with venetoclax at any line, 100 (15.8%) received BCL2 +/- anti-CD20 as first-line; 170 (26.9%) as second line (125 previously treated with CIT, 27 with BTKi); and, 361 as third or subsequent line. ORR ranged between 71.5% (≥3 lines) with 30.5% CR/CRi to 90.3% (first-line) with 68.1% CR/CRi. Treatment discontinuation was due to toxicity in 28.6% of patients treated in the first-line, and 17.6% and 21.8% of patients treated in second and third-or-higher-line, respectively. Disease progression led to treatment discontinuation in 14.3%, 20.6% and 33.6% in first, second and third-or-higher line, respectively. CIT was used as front-line treatment in 5465 patients (59.6%). Of these, 2070 (37.9%) and 1018 (18.6%) patients received a second and third line of treatment, respectively. The great majority (865/1086 cases, 79.7%) of patients who received a second line before 2014 were retreated with CIT, most commonly Bendamustine-Rituximab (284/1086, 26.1%) and Fludarabine-Cyclophosphamide-Rituximab (252/1086, 23.2%); alemtuzumab monotherapy was used in 55/1086 (5%) of patients. After 2014, 415/984 patients (42.1%) were retreated with BTKi; 93 (9.5%) with venetoclax; 70 (7.2%) with idelalisib; 50 (5%) with Alemtuzumab monotherapy, and 315 (32%) with CIT. Similarly, in the third-or-higher line of treatment, most patients (86.3%) were retreated with CIT before 2014, while BTKi, BCL2i, and PI3Ki were mainly used after 2014 (in 43.1%, 15.7% and 14.7% of cases, respectively). Finally, our cohort included 1075 patients with TP53 aberrations. The ORR of patients receiving BTKis (n=171) as first-line of treatment was 86.5% (22.2 CR+64.3 PR), while the ORR with venetoclax +/- anti-CD20 (n=15) was 91% (45.5% CR+45.5 PR). Patients treated with CIT (n=694) had an ORR of 68.7% (28.3% CR+40.4% PR). In conclusion, in a large international study we provide real world data regarding the selection and sequencing of treatment in CLL, charting a major shift in treatment patterns before and after the introduction of novel trargeted agents and confirming their efficacy even in high-risk CLL. Disclosures Scarfo: Janssen: Honoraria, Other: Travel grants; Astra Zeneca: Honoraria; Abbvie: Honoraria. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Collado: Abbvie,: Other: pharmaceutical Company, Research Funding; Janssen: Other: Pharmaceutical Company, Research Funding. Galimberti: AbbVie, Janssen: Honoraria, Other: Travel grants; Incyte: Speakers Bureau. García-Serra: AbbVie: Other: Educational grands; Janssen: Other: Educational grants; Novartis: Other: Educational grants. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Hatzimichael: Amgen, Roche, Genesis, Novartis, Bristol Mayer Squibb, Celgene, Pfizer: Consultancy; Abbvie, Amgen, Bristol Mayer Squibb, MSD, Gilead, Janssen Cilag, Genesis Pharma, Roche, Takeda: Honoraria. Herishanu: AbbVie: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Medison: Honoraria. Jaksic: Roche, Oktal-Pharma/Celtrion, Sandoz: Consultancy, Honoraria. Kater: Janssen, AstraZeneca: Other: Ad Board, steering committee, Research Funding; Abbvie: Honoraria, Other: Ad Board, Research Funding; BMS, Roche/Genentech: Other: Ad Board, , Research Funding; Genmab, LAVA: Other: Ad Board, Steering Committee. Kotsianidis: Astellas: Other: NONE, Research Funding, Speakers Bureau; Genesis: Consultancy, Other: NONE; Janssen Hellas: Consultancy, Other: NONE, Speakers Bureau; Bristol Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Novartis Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Abbvie: Consultancy, Other: NONE, Research Funding, Speakers Bureau. Kreitman: NIH: Patents & Royalties: Moxetumomab Pasudotox; Genentech: Research Funding; Teva: Research Funding; AstraZeneca/MedImmune: Research Funding; Innate: Research Funding; GSK/Novartis: Research Funding; Array BioPharma/Pfizer: Research Funding. Laribi: BeiGene: Other: Personal Fees; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Novonordisk: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Celgene: Other: Speaker Honoraria; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding. Milosevic: Roche: Honoraria; Abbvie,: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Reda: Beigene: Consultancy; Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Šimkovič: Janssen, Gilead, Roche, AstraZeneca, and AbbVie: Other: consultancy fees, advisory board participation fees, travel grants, and honoraria; University Hospital Hradec Kralove: Current Employment; AbbVie: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Merck: Current equity holder in publicly-traded company; Eli Lilly: Current equity holder in publicly-traded company; J&J: Current equity holder in publicly-traded company; Gilead: Other: Travel, Accommodations, Expenses. Špaček: AbbVie, AstraZeneca, Gilead, Janssen, and Roche: Honoraria. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Visentin: Italfarmaco and Gilead: Speakers Bureau. Vassilakopoulos: AstraZeneca: Honoraria; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Dr. Reddy's: Research Funding; Novartis: Consultancy, Honoraria; GlaxoSmithKline: Honoraria, Other: Travel; Merck: Honoraria, Research Funding; Integris: Honoraria; Roche: Consultancy, Honoraria, Other: Travel; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; AbbVie: Consultancy, Honoraria; Karyopharm: Research Funding. Vitale: Janssen: Honoraria. Yáñez: Gilead-Kite, Janssen, AbbVie, AstraZeneca, Beigene, Roche, Pfizer, Jazz, BMS, and Merck: Other: Advisory board participation fees ; Janssen, AbbVie, AstraZeneca, Gilead-Kite, Roche, Pfizer, and Merck: Speakers Bureau. Antic: AbbVie, Janssen, and Roche: Honoraria. Coscia: Janssen: Honoraria, Other, Research Funding; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria, Other. Cuneo: AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Gaidano: Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; 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. Guièze: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Laurenti: AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Tam: Beigene: Research Funding; Janssen: Research Funding; Abbvie: Research Funding; Loxo: Honoraria; Beigene: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Trněný: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Bosch Albareda: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Abbvie: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Kite: Honoraria; Sanofi: Honoraria; Lilly: Honoraria. Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Chatzidimitriou: Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Ghia: AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding. Stamatopoulos: AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, 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

Background Autologous peripheral blood marrow stem cell transplantation (auto-PBSCT) preceded by high-dose chemotherapy is a well-known method of treatment for patients with hematological cancers. Performing the procedure entails obtaining from the patient their own stem cells from peripheral blood using G-CSF. Currently, various filgrastim biosimilars are widely used. Aim of the study The purpose of this study is to compare the efficacy and safety of three different biosimilars of filgrastim in PBSC mobilization in patients with hematological malignancies. Materials and methods This is a retrospective analysis of 282 patients (118 women and 164 men) who underwent stem cells mobilization for auto-PBSCT in the Department of Hematology in Wroclaw in 2012-2014. Three filgrastim biosimilars were used: Tevagrastim (95), Nivestim (92), and Zarzio (95). Ninety patients (32%) were diagnosed with multiple myeloma, 55 (19%) with Hodgkin's lymphoma, 90 (32%) with NHLs, 20 (7%) with acute myeloid leukemia, and 27 (10%) with another hematological cancer. Results The mean number of CD34+ cells collected during the first leukapheresis was 5.95 × 106 /kg for Tevagrastim, 7.08 × 106 /kg for Nivestim, and 6.8 × 106 /kg for Zarzio (P > .05). The necessary number of leukapheresis for patients receiving Zarzio, Nivestim, and Tevagrastim was 1.32, 1.37, and 1.66, respectively (P > .05). The percentage of effective mobilizations was 88.2% for Zarzio, 86.2% for Nivestim, and 84.9% for Tevagrastim. The side effects included bone pain and headache. Conclusion All tested biosimilars demonstrated similar effectiveness and safety profiles in patients with hematological tumors undergoing PBSC mobilization; therefore, they can be used interchangeably.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/β and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/β and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

Highlights • Patients with haematological malignancies and COVID-19 are characterized by T lymphopenia and reduction in NK cell numbers. • T lymphopenia in haematological patients with COVID-19 include reduction in CD4+ T cells numbers and lowered CD4/CD8 ratio. • Increase in activated T cells with low CD4/CD8 ratio are crucial for the early stages of COVID-19 in haematological patients. • Low levels of both TCRγ/δ and CD3+CD25+ T cells may indicate impaired cellular response to COVID-19 in haematological patients., The role of immune dysregulation in the course and prognosis of COVID-19 is not clearly established. In particular, immune status in specific populations such as haematological patients, who have an impaired immunological system, has not been described so far. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subsets in 27 SARS-CoV-2-infected patients, including 16 patients with haematological malignancies. We identified T cell subpopulations, B cells, NK cells and TCR α/ß and ɣ/ƍ-expressing T cells during COVID-19 infection, with significant changes observed in immune profiles during the course of disease, especially in haematological patients. We observed an increase in activated T lymphocytes (CD3+HLA-DR+ and CD3+CD8+HLA-DR+) in the early stages of SARS-CoV-2 infection with a concomitant decrease in the CD4/CD8 ratio in haematological patients compared to non-haematological patients affected by COVID-19. We also found a decrease in ɣ/ƍ T cells in both studied groups of patients, with lower numbers of CD25+ T cells and CD16+CD56+ NK cells in haematological patients compared to non-haematological patients with COVID-19. Our findings demonstrate, for the first time, impaired adaptive immunity in patients with haematological malignancies infected with COVID-19, resulting in impaired cellular immune responses to SARS-CoV-2. This warrants further investigation of this disease group in COVID-19 patient cohorts

Patients with hematological malignancies (HM) require intensive chemotherapy with curative intent, especially in case of AML that results in more frequent admissions to Intensive Care Units (ICU). Due to our knowledge, this study is the first multicenter retrospective analysis in Polish population. A total of 200 patients with HM hospitalized in 4 Polish hematological centers. Data concerning clinical indices and outcomes during admission and ICU stay were collected retrospectively. The most common hematological malignancy was acute leukemia (55%). The main cause of ICU admission was respiratory failure (88.5%), often accompanied by sepsis (58.5%) and acute renal failure (51.5%). In patients with hematological malignancies, the following factors were associated with ICU mortality: prolonged ICU stay (odd ratio [OR] = 6.98, 95% confidence interval [CI]: 1.38-35.33, χ2 = 5.61, p = 0.02), the presence of acute respiratory failure (odd ratio [OR] = 5.35, 95% confidence interval [CI]: 1.01–28.46, χ2 = 3.93, p = 0.04), and the need for renal replacement therapy (odd ratio [OR] = 8.75, 95% confidence interval [CI]: 1.23–62.11, χ2 = 4.78, p = 0.03). There were following associations with in-hospital mortality in patients with hematological malignancies: prolonged ICU stay (odd ratio [OR] = 10.12, 95% confidence interval [CI]: 1.85–55.37, χ2 = 7.21, p = 0.008), the presence of acute respiratory failure (odd ratio [OR] =5.24, 95% confidence interval [CI]: 1.36–20.16, χ2 = 5.87, p = 0.02), the need for catecholamine support (odd ratio [OR] =3.43, 95% confidence interval [CI]: 1.06–11.05, χ2 = 4.32, p = 0.04), and renal replacement therapy (odd ratio [OR] =5.55, 95% confidence interval [CI]: 1.14–26.92, χ2 = 4.59, p = 0.03). We have demonstrated that ICU and in-hospital mortalities among patients with hematological malignancies are still poor, but easier access to the intensive care unit and close cooperation between hematologists and intensivists may improve outcomes. We have found that acute failure of key organs (acute respiratory failure, end-stage renal failure requires renal replacement therapy) and length of ICU stay (but probably no comorbidities and illness severity) may have impact on mortality (both ICU and in-hospital).

Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. It is the most common acute leukemia and is a highly heterogeneous disease. AML leads to impaired hematopoiesis, which may result in increased risk of infection. Toll-like receptors (TLRs) are major elements of the innate immune system which recognize pathogen-associated molecular patterns. They also have a role in autoimmune diseases and cancer through their recognition of endogenous danger-associated molecular patterns. Various TLRs were found to be expressed in AML cells, and their expression was found to affect growth, differentiation, and immunostimulatory capacity in AML. We retrospectively analysed 90 patients (48 females and 42 males) with diagnosis of AML, hospitalized in Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation of Wroclaw Medical University. The median age of patients was 62 (range:18-81). Infectious complications after induction chemotherapy occurred in 62 patients. In the present study, we detected the effect of seven single nucleotide polymorphisms (SNPs) located in the genes coding for TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790) and TLR9 (rs187084, rs5743836). DNA was isolated from samples of peripheral blood taken on EDTA. Melting curve genotyping with the use of LightSNiP asays(TIB MOLBIOL, Germany) was employed to determining TLR3, TLR4 and TLR9 genotypes, and the reactions were performed LightCycler 480 device (Roche Applied Science, Germany).Statistical analyses were performer using Real Statistics Resource Pack for Microsoft Excel. We found that TLR3 rs5743305 AA homozygosity was more common in AML patients with infectious complications than in patients unaffected by infections (p=0.015). TLR4 rs4986791 C and TLR9 rs5743836 C were associated with lower levels of the inflammation marker CRP (p=0.015 and p=0.048, for rs4986791 and rs5743836, respectively), TLR4 rs4986791 C and was less frequently detected among patients with CRP>5 (p=0.028). We also found TLR9 rs187084 C to be more common in patients with adverse cytogenetic risk according to ELN criteria (0.012). Additionally, a trend for higher prevalence of extramedullary disease was observed for carriers of TLR3 rs3775296 T (p=0.054), TLR3 3775291 GG (p=0.068), TLR4 rs4986790 G (p=0.078), as well as TLR9 rs187084 TT (p=0.053). In conclusion, our results suggest that SNPs in the genes coding for TLR3, TLR4 and TLR9 may be implicated in clinical outcome of AML and is related with increased risk of infectious complications. Disclosures Wróbel: BMS: Honoraria; Roche: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; BeiGene: Honoraria.

Introduction: Obinutuzumab-based induction immunochemotherapy was demonstrated to improve the outcome of patients with follicular lymphoma (FL) comparing to the regimens with rituximab in GALLIUM study (NCT01332968). The infusion related reactions (IRRs) occur in more than half of FL patients during the first obinutuzumab administration. Therefore, during the whole treatment period infusions lasting more than 3-4 hours are so far recommended. Shorter infusions would be more convenient for both patients and medical staff and could also contribute to the shorter hospitalization that is desirable during COVID-19 pandemic. The aim of the study was to evaluate the tolerance and early efficacy of obinutuzumab-based regimens in FL patients in clinical practice. Methods: We evaluated tolerability of obinutuzumab infusions and response rates to different regimens of chemotherapy combined with obinutuzumab in consecutive FL patients treated in hemato-oncology centers in Poland from Jan 2020 to Jan 2021. Obinutuzumab was combined with CHOP, CVP or bendamustine according to the treating physician choice. Obinutuzumab maintenance was offered to the patients who achieved at least partial response (PR) after induction immunochemotherapy. Response was evaluated with computed tomography or positron emission tomography according to 2014 Lugano criteria. Adverse events were assessed according to Common Toxicity Criteria (version 5). Results: The study group included 129 treatment-naive FL patients. The median age (range) was 52 (29 - 90) years, 35.7% of patients were males. According to FLIPI 46.5 % of patients were classified as high risk, 33.3% as intermediate and 20.2% as low risk, whereas 33.7%, 30.4% and 35.9% of patients were in PRIMA PI high, intermediate and low risk groups, respectively, Table 1. Median number of GELF criteria was 2 (range 1-6). Induction chemotherapy included: CVP in 48.1% (n=62), CHOP in 29.5% (n=38) and Benda in 22.5% (n=29) of patients. Median number of cycles was 6 (range 1 - 8). Maintenance was started in 85 patients (76.6%). The first obinutuzumab dose was administered as a single infusion during the first day of the first cycle in 43.4% of patients (n=56), whereas 56.6 % (n=73) of patients had initial infusion divided into 2 days (100 mg and 900 mg). During the first cycle 93.8% (n=121) of patients received three doses of obinutuzumab. The doses were omitted in 8 patients: in 4 due to Covid-19, in 1 due to pneumonia and neutropenia and in 3 cases due to neutropenia. IRRs were reported during the first Obinutuzumab administration in 10.1% of patients (n=13, grade 1/2 in 11 and grade 3 in 2 patients): in 7 patients who received obinutuzumab initial dose in single infusion and in 6 patients who received first obinutuzumab dose divided in two days. Median time of the first infusions was 4 hours and 55 min (range 1:30 - 9:45). There were no IRRs reported during the subsequent obinutuzumab infusions. The most common adverse event was neutropenia with grade 3/4 events reported in 51.1% of patients (n=66). G-CSF support was given in 70.4% (n = 81/115), and as the primary prophylaxis in 42.6 % (n=49) of patients. The SARS-CoV-2 infection occurred in 19 patients regardless of initial chemotherapy regimen. After induction immunochemotherapy complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) rates were: 71.8%, 23.9%, 0.9% and 3.4%, respectively, Table 2. With a median follow up of 8.7 months 5 patients (3.9%) relapsed, 4 died due to COVID infection. There were no deaths caused by FL. Conclusions: In our study obinutuzumab-based induction treatment was well tolerated. The low incidence and low grade of infusion related reactions in most of the patients, reported only during the first infusion, support the practice of administration of the first obinutuzumab dose in a single infusion. For convenience, the concept of short, 90 minutes infusion of Obinutuzumab starting from the second cycle could be considered (Canales MA, EHA 2021). During COVID-19 pandemic using obinutuzumab with chemotherapy is feasible and justified by the high response rate to this treatment. Figure 1 Figure 1. Disclosures Paszkiewicz-Kozik: Roche: Honoraria, Other: congress fee; Servier: Other: congress fee; gillead: Other: travel grant; Takeda: Honoraria, Other: Travel Grants. Hus: Astra Zeneca: Honoraria, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Romejko-Jarosinska: roche: Other: congress fee; servier: Other: congress fee; gilead: Other: traver grant. Drozd-Sokolowska: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka: Janssen: Consultancy, Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Acerta Pharma: Research Funding; AbbVie: Research Funding; Macrogenics: Research Funding; Beigene: Research Funding; MEI Pharma: Research Funding; Incyte Corp.: Research Funding; Takeda: Research Funding. Lech-Marańda: Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: 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; Roche: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Walewski: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Servier: Consultancy, Honoraria.

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients.

BACKGROUND There are several regimens used in hematopoietic stem cell (HSC) mobilization in multiple myeloma (MM). Cyclophosphamide (Cy) is one of the most commonly used agents, although it does not always result in collecting adequate number of CD34+ cells. Recently, cytarabine (Ara-C) has been proposed as potentially efficient and safe option. AIMS Since the data regarding Ara-C in HSC mobilization is limited, the aim of our study was to compare retrospectively the efficiency and toxicity of G-CSF combined with either Ara-C or Cy in MM patients. MATERIALS & METHODS Of a total of 89 patients, 43 received low or intermediate doses of Cy, and 46 were treated with 800 mg/m2 /day of Ara-C administered for two days. RESULTS The mean peak of CD34+ cells/ul in peripheral blood was 132 (range, 84-202) in Ara-C and 51 (range, 29-69) in Cy cohort (p < 0.001). The median number of collected CD34+ cells (×106/kg) was 10.3 (range, 4.2-17.9) vs 4.5 (range, 2.7-8.9), respectively (p < 0.001). Mobilization failure was observed in one patient in Ara-C cohort (2%) and in 8 patients treated with Cy (19%) (p = 0.013). In the Ara-C group 98% of patients obtained more than 4×106 CD34+ cells/kg required for tandem transplantation. Moreover, we observed a trend toward increased paraprotein levels measured at transplant compared to before HSC mobilization in Ara-C cohort and significantly higher transfusion rates in that group. CONCLUSION Our findings confirm higher HSC mobilization efficacy of Ara-C compared to Cy in MM patients. However, lower transfusions rate and better disease control of Cy may justify its use in some cases.

Highlights • Higher mortality rate in COVID-19 patients with haematologic diseases. • Haematologic patients with COVID-19 have 50 % less chance of survival. • Probability of death was higher in patients older than 40 yrs of age with AML/MDS., Background Here we report nosocomial outbreak of COVID-19 among patients in a haematological unit. To our knowledge this is the first report from Central Europe comparing morbidity and mortality in infected and non-infected patients after exposure to SARS-CoV-2. Methods The outbreak involved 39 individuals: 19 patients and 20 health care workers. The SARS-CoV-2 test by nasopharyngeal swabs was performed by real-time RT-PCR. Exposed patients were divided into two groups: quarantine patients with and without COVID-19. All patients were prospectively examined at the following time points: 0, 7 days, 14 days, 21 days and 28 days after confirmation or exclusion of SARS-CoV-2. Results Infection was confirmed in a total of 5/20 health care workers and 10/19 patients. Among the patients positive for SARS-CoV-2 infection, the mortality rate was 36.8 %. The probability of death in patients infected with SARS-CoV-2 increased 8-fold (p = 0.03). Bacterial, fungal, and viral co-infection significantly decreased survival in these patients (p

Background: The hormonal metabolism of adipose tissue differs across regions of fat. This issue has never been verified in male patients with coronary artery disease (CAD) with and without systolic...

Iron deficiency (ID) may be an important, treatable co-morbidity complicating cardiovascular diseases, but considerable uncertainty exists about the diagnostic accuracy of blood tests. Accordingly, we investigated the relationship between blood tests for ID and iron stores in bone marrow aspirates, the diagnostic gold-standard for ID, in patients with stable coronary artery disease (CAD).Bone marrow aspirates were obtained from 65 patients with stable CAD undergoing cardiac surgery and 10 healthy controls. ID was defined as depleted extracellular iron stores (0-1 grade according to Gale scale) accompanied by ≤10% of erythroblasts containing iron.Bone marrow ID was found in 31 (48%) patients with CAD but in none of the controls (p0.01). Amongst patients with CAD, ID was present in 10 of 16 (63%) with and 21 of 49 (43%) without anaemia (p=0.17). The clinical profiles of patients with and without ID were similar. Of circulating biomarkers of ID, serum soluble transferrin receptor had the strongest association with bone marrow ID (area under curve: 0.876±0.048, 95% confidence interval: 0.762-0.948, for cut-off of ≥1.32mg/L-sensitivity: 67%, specificity: 97%).Almost half of patients with stable CAD have profound bone marrow iron depletion that can be accurately assessed non-invasively using serum soluble transferrin receptor.

We sought to determine and compare clinical profile and management of outpatients with heart failure with reduced ejection fraction (HFREF) treated by cardiologists and general practitioners (GPs) in Poland.All the 790 randomly selected cardiologists and GPs in the DATA-HELP registry, which included 5563 patients, filled out questionnaires about 10 consecutive outpatients with HFREF.Outpatients managed by GPs were older (69±10 vs 66±12 years), and the prevalence of men was less marked (58% vs 67%). They also had higher left ventricular ejection fraction (38±6% vs 35±8%) and had more pulmonary congestion (63% vs 49%) and peripheral oedema (66% vs 51%), compared with those treated by cardiologists (all p0.001). Hypertension (74% vs 66%), previous stroke and/or transient ischaemic attack (21% vs 16%), diabetes (40% vs 30%), and chronic obstructive pulmonary disease (14% vs 11%) were more common in outpatients of GPs (all p0.001). GPs were less likely to prescribe β-blocker (95% vs 97%, p0.01), mineralocorticoid receptor antagonist (MRA) (56% vs 64%, p0.001), and loop diuretic (61% vs 64%, p0.05) or use PCI (33% vs 44%, p0.001), CABG (11% vs 16%, p0.001), ICD (4% vs 10%, p0.001), or CRT (1% vs 5%, p0.001). Prescription of renin-angiotensin system inhibitors (94% vs 94%, p0.2) and digoxin (20% vs 21%, p0.2) by GPs and cardiologists was similar.In contemporary Poland, most outpatients with HFREF receive drugs that improve survival and undergo revascularisation procedures, although devices are rare, but the clinical profiles and management of those treated by GPs and cardiologists differ. Outpatients treated by GPs are older and have more co-morbidities. Outpatients treated by cardiologists more commonly receive β-blocker, MRA, ICD, and CRT, and undergo coronary revascularisations.

Deficiencies of anabolic hormones are common in men with heart failure (HF). It remains unclear whether the deranged metabolism of these hormones is the pathophysiological element of HF itself or is the consequence of co-morbidities or/and treatment in HF.We examined 382 men with systolic HF. Serum hormones (i.e. total testosterone [TT], DHEAS, IGF-1) were assessed using immunoassays, serum free testosterone (eFT) - using the Vermeulen equation.Prevalence of TT and eFT deficiencies was similar in men with HF agedversus ≥60 years (23% and 32% for TT and eFT deficiencies). Deficiencies in DHEAS and IGF-1 were more common in younger (63% and 92%) than older patients (48% and 73%). In men60 years, TT deficiency was accompanied by the therapy with digoxin, eFT deficiency - the therapy with digoxin and the presence of diabetes, DHEAS deficiency - the therapy with loop diuretic (all p0.05). In men ≥60 years, TT deficiency - the therapy with loop diuretic, DHEAS deficiency - the therapy with spironolactone and digoxin, and hsCRP, IGF-1 deficiency - the high hsCRP (all p0.05).Deficiencies in anabolic hormones are common in younger and older men with HF. Some therapies (but not major co-morbidities) may contribute to anabolic deficiencies.

Tetralogy of Fallot is the most common cyanotic congenital heart disease. Total surgical correction of this defect during infancyallows for long-term survival in most of the patients. The long-term prognosis for untreated tetralogy of Fallot is poor and patients who have not undergone total surgical repair rarely live to old age. We present a case of 67-year-old man with not corrected tetralogy of Fallot diagnosed at the age of 44 years without typical clinical symptoms.