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Background: Ropeginterferon alfa-2b demonstrated efficacy and safety in patients with polycythaemia vera in the PROUD-PV and CONTINUATION-PV multicentric randomised studies. These studies reported the superior effect of ropeginterferon alfa-2b in attaining haematological and molecular remission during the fourth and fifth year of therapy. Patients and Methods: A total of 14 Ph-MPN patients treated with ropeginterferon alfa-2b at our Dept. of Internal Medicine – Haematology and Oncology were analysed from May 2020 to July 2022. Therapy duration, dosing, effect, and tolerance were evaluated. Results: Therapy median duration was 266 days. 14 patients in total were treated; 11 had polycythaemia vera (79%), 2 had essential thrombocythemia (14%), and one patient had secondary myelofibrosis post polycythaemia vera (7%). The median ropeginterferon alfa 2-b dose was 150 μg. Complete haematological remission was attained in 11 (79%) patients. Two patients (14%) had to discontinue treatment. During therapy, six patients (43%) suffered adverse events; only one patient (7%) developed a thromboembolic event. Conclusion: Our initial experience has confirmed the promising effect of ropeginterferon alfa 2-b on haematocrit control and its excellent tolerance among patients. [ABSTRACT FROM AUTHOR]

COVID-19 caused by SARS-CoV-2 is a life-threatening global pandemic disease that has led to high mortality for over two years. Elderly individuals with comorbidities and immunocompromised patients are particularly at risk. Scientifi c research eff orts are therefore intensively focused on the development and optimization of COVID-19 treatment. Early treatment with SARS-CoV-2-neutralizing monoclonal antibodies has been shown to be eff ective both in vitro and in clinical practice in patients at high risk of disease progression to severe COVID-19. This paper summarizes the potential clinical benefi ts of the recently approved monoclonal antibody combination tixagevimab and cilgavimab for COVID-19 prevention and treatment. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) reactivation after allogeneic haematopoietic stem cell transplantation and its subsequent antiviral treatment is a significant complication leading to increased morbidity and mortality in these patients. Frequent monitoring of CMV viremia with early pre-emptive antiviral treatment in case of CMV reactivation represents the most widely used option to date for preventing CMV disease. While this approach leads to a low incidence of CMV disease, the percentage of CMV reactivations requiring pre-emptive therapy remains high and increased morbidity and non-relapse mortality are thus associated with CMV reactivation per se. Letermovir is a new antiviral drug with anti-CMV activity approved for use in CMV seropositive patients after allogeneic hematopoietic stem cell transplantation. A randomized, placebo-controlled study that led to the introduction of letermovir into clinical practice demonstrated a positive effect in reducing the incidence of clinically significant CMV infection as well as non-relapse mortality compared to placebo, especially in patients at high risk of CMV disease. Although it is already commonly used in primary CMV prophylaxis after allogeneic hematopoietic transplantation, its use is associated with certain unresolved issues such as the optimal duration of prophylaxis or its use in secondary prophylaxis or pre-emptive treatment of CMV reactivation. The following article summarizes currently available data on the use of letermovir in patients after allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

This article describes a case of highly suspected isolated diffuse kidney infiltration by myeloid leukemic cells, without primary bone marrow involvement or any pathological imaging findings in a patient presenting with fever of unknown origin, acute kidney injury, microcytic anaemia, weight loss, anorexia, dry cough and mild splenomegaly. This complex dia-gnostic process thus required repeated bio-psy of both bone marrow and kidney, which subsequently ruled out leukemic infiltration. The presenting symptoms and pathological laboratory findings responded promptly to corticosteroid treatment, and our patient was finally dia-gnosed with tubulointerstitial nephritis. [ABSTRACT FROM AUTHOR]

Background: Our MIND database was initiated on May 1, 2013, with the primary objective of collecting data from patients with Ph negative myeloproliferative neoplasms (Ph-MPN) in Czech haematological centres. The principal aim was to analyse and compare our patient data with published data. Patients and Methods: A total of 641 valid Ph-MPN patients registered in MIND were analysed from 2013 to 2020. Epidemiology, dia-gnostics, therapy and prognosis were evaluated. Results: With a 35-month median follow-up, the most common dia-gnosis was polycythaemia vera- PV (34%) followed by primary myelofibrosis, PMF (31%) and essential thrombocythemia, ET (22%). At the time of dia-gnosis, patients suffered mostly from fatigue (52%), night sweats (32%), weakness (30%) and itching (27%). Splenomegaly occurred in more than half of PMF patients (54%). The JAK2 V617F mutation was present in 90% of PV, 65% of PMF and 62% of ET, respectively. The CALR mutation was found in 22% of ET and 16% of PMF, respectively. Cytogenetic abnormalities were significantly more frequently documented in both PMF and PV compared to ET (17 and 15 vs. 3% of examined patients, respectively; P ≤ 0.005). Thrombosis (22%) and bleeding (10%) were the most common complications at dia-gnosis with no significant difference in frequency among PV, ET, and PMF, respectively (P > 0.017). In PV, hydroxyurea was the most frequently used drug as both 1st and 2nd line treatment (72 and 65%, respectively). Anagrelide was used in both lines in ET (52 and 82%, respectively) and hydroxyurea was used as 1st line treatment with ruxolitinib as 2nd line treatment in PMF (70 and 30%, respectively). Leukemic transformation was detected in 3% of Ph-MPN and only in MF (10%). 17% of our patients died, most from PMF (53%). Median overall survival was not attained in ET, contrasting with the lowest median in secondary MF (2.5 years). In PMF, median overall survival was decreased by dotage, higher IPSS, and JAK2 V617F mutation presence. Conclusion: We have recognized a recurring definitive frequency of symptoms that exacerbate patient quality of life. A higher incidence of additional cytogenetic abnormalities was recorded more frequently with both PMF and PV compared to ET. During dia-gnosis, thrombotic and bleeding events were present with no significant difference in frequency among PV, ET, and PMF. Overall survival median was the longest in PV, compared to MF with the most frequent leukemic transformations and the lowest survival. In PMF, higher age, higher IPSS and JAK2 V617F presence were shown as factors shortening survival. [ABSTRACT FROM AUTHOR]

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Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Invasive fungal diseases are life-threatening infectious complications affecting haematological patients and their early diagnosis can contribute to improved survival of affected patients. In the last years, the patterns of invasive fungal infections have changed mainly due to the selection pressure of antifungals. Material and Methods: The aim of our analysis to evaluate retrospectively changes in the epidemiology of invasive aspergillosis, invasive candidiasis and rare mycoses in haematological patients at Czech and Slovak haematological centres from 2005–2017. The observed period was divided into: 2005–2012 (1st period) and 2013–2017 (2nd period). Data entered into FIND – Fungal INfection Database (according to the EORTC/MSG criteria from 2008) was used for the analysis. The total consumption of posaconazole and micafungin was expressed in relative annual consumption per 1000 bed-days. Results: A total of 349 invasive aspergillosis, 168 invasive candidiasis and 102 rare mycoses (65.7% invasive zygomycosis) were documented. The incidence of aspergillosis increased from 2005 to 2012, with a declining trend since 2013 (the average number of cases per centre in 2005–2012–2017 was: 1.1–3.6–0.7). The incidence of aspergillosis in high risk patients decreased (2005 – 72.7%, 2013 – 42.4%, 2017 – 18.2%). Total consumption of posaconazole has been on the increase since 2005 (rDDD in 2005-2010-2015: 0-831-1043). The total number of invasive candidiasis and rare mycoses remained unchanged over the years. The Candida albicans vs. non-albicans ratio remained unchanged in the 1st and 2nd periods (26.1% vs. 29.1%, p=0.732). There was a significant increase in rare mycoses in breakthrough infections on posaconazole or voriconazole prophylaxis compared to non-breakthrough infections (35.3% vs. 14.4%). Conclusion: Based on our analysis, we have confirmed a decrease in the incidence of invasive aspergillosis from 2013 after the introduction of routine antifungal prophylaxis with posaconazole in high-risk patients. The ratio of high-risk patients with invasive zygomycosis has also decreased. Patients on posaconazole or voriconazole prophylaxis have changed the spectrum of infections in favour of rare pathogens. [ABSTRACT FROM AUTHOR]

Asplenic patients are at significant risk of infectious complications. The most prevalent pathogens causing infections in this high-risk group include encapsulated bacteria, especially Streptococcus pneumonia. The most serious form of infection in asplenic patients is septic syndrome, commonly referred to as "overwhelming post-splenectomy infection". All asplenic patients are at the risk of this infection characterised by a highly dramatic clinical course. However, patients splenectomised for haematological diseases are those at greatest risk in this group. Moreover, the risk of infection is increased by ongoing oncological treatment or immunosuppressive therapy. The risk of infection can be reduced by simple preventive measures: adequate patient education and emergency antibiotics, vaccination against selected pathogens according to current recommendations and antibiotic prophylaxis in indicated cases. Based on the updated international recommendations, especially in the field of vaccination, new recommendations of the CzEch Leukemia Study Group for Life (CELL) for the prevention of infectious complications in haematological patients after splenectomy have been drawn up and are presented in this paper. [ABSTRACT FROM AUTHOR]

Central venous catheters are routinely used as a venous access in haematological patients requiring intensive care or parenteral chemotherapy. Despite its many benefits, the use of central venous catheters can be associated with several complications. The most serious and most common complications are catheter related bloodstream infections that significantly increase morbidity and mortality of patients with haematological malignancy. On behalf of the Czech leukaemia group for Life (CELL), a retrospective analysis of the use of central venous catheters and the results of microbiological examination of extracted central venous catheters at haematological centres in Czech Republic and Slovakia was performed. A short questionnaire was used for this purpose. Data from 2015 from 7 adult and 4 paediatric centres were evaluated. A total of 3195 central venous catheters were inserted in the centres involved, whereby short-term catheters were used 4 times more often than long-term catheters. The preferred subtype of short-term catheter according to the site of insertion were catheters inserted via the subclavian vein (49.7%), however there were significant differences between centres. On average - 45% of the extracted catheters were sent for microbiological examination. A significantly higher proportion of catheters were thus examined in paediatric centres compared to adult centres (65.3% vs. 33.5%). Positive culture results were found on average in 20 % catheters examined microbiologically. Most frequently, catheter tip cultures involved gram positive cocci, mostly coagulase negative staphylococci and Staphylococcus aureus. When coagulase negative staphylococci were excluded, gram negative bacteria namely Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, were the most prevalent findings. No significant differences were found in Czech and Slovak haematological centres when compare to international data and recommendations. Nevertheless, significant differences between individual centres were observed and thus we believe that more strict compliance with current international recommendations for the prevention and diagnosis of catheter related infections is required. These guidelines are also part of this manuscript. [ABSTRACT FROM AUTHOR]

Our observational study analysed fungal infection frequency within cohorts with versus without antifungal prophylaxis (AFP) among newly diagnosed first-line venetoclax and azacitidine (VEN + AZA)-treated acute myeloid leukaemias in Czech, Austrian and Slovak haematology centres. Among 186 patients, 85 (46%) received antifungal prophylaxis, while 101 (54%) received no prophylaxis. Fungal infections occurred in 1/85 patients with prophylaxis (1%) and 5/101 patients without prophylaxis (5%) (p = 0.222). No significant difference was recorded between cohorts with and without AFP in terms of death rate (p = 0.296) and overall survival (p = 0.844). In conclusion, most infections were not severe, developing during the first treatment-cycle and did not affect patients' overall outcome., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 10 9 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail., Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy., Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment., Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is only limited data on cytomegalovirus (CMV) prophylaxis with high-dose (HD) aciclovir after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective analysis on a total of 179 patients who underwent their allo-HSCT with HD-aciclovir prophylaxis at our center. A clinically significant CMV infection (cs-CMVi) was observed in 56 (31%) cases with a median time of 49 (range 25-147) days after HSCT. A significantly higher CMV infection rate was observed in seropositive recipients with a seronegative donor (74%) compared to seropositive recipients with a seropositive donor, and seronegative recipients with seropositive and seronegative donors (24%, 18%, 7% respectively; p < 0.001). The CMV serostatus was the only significant risk factor for CMV infection in our analysis. CMV disease developed in three patients with CMV-related death in two cases. During HD-aciclovir prophylaxis, we did not observe any medical condition attributable to HD-aciclovir's adverse effects. Compared to published results, we observed a low incidence of cs-CMVi with HD-aciclovir prophylaxis in several patient subgroups, especially in seropositive recipients with a seropositive donor. With respect to the determined threshold, HD-aciclovir prophylaxis seems to have good efficacy in an intermediate cs-CMVi risk patients, but prospective randomized trials would be needed for definite conclusions., (© 2023. The Author(s).)

Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies., Methods: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir., Results: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death., Conclusions: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19-caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients., Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir., Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration., Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir., Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)., Competing Interests: The authors do not declare conflicts of interest related to the submitted manuscript. The funder of the study had no role in study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication., (© 2023 The Author(s).)

Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT., Methods: This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022., Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53)., Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Busca, Salmanton-García, Marchesi, Farina, Seval, Van Doesum, De Jonge, Bahr, Maertens, Meletiadis, Fracchiolla, Weinbergerová, Verga, Ráčil, Jiménez, Glenthøj, Blennow, Tanase, Schönlein, Prezioso, Khanna, Duarte, Žák, Nucci, Machado, Kulasekararaj, Espigado, De Kort, Ribera-Santa Susana, Marchetti, Magliano, Falces-Romero, Ilhan, Ammatuna, Zompi, Tsirigotis, Antoniadou, Zambrotta, Nordlander, Karlsson, Hanakova, Dragonetti, Cabirta, Berg Venemyr, Gräfe, Van Praet, Tragiannidis, Petzer, López-García, Itri, Groh, Gavriilaki, Dargenio, Rahimli, Cornely, Pagano and EPICOVIDEHA Consortium.)

Background: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies., Methods: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia., Results: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2-78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p < .0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p = .001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396-5.204, p = .003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151-4.376, p = .018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102-7.601, p < .001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192-5.222, p = .015)., Conclusions: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome., (© 2022 Wiley-VCH GmbH.)

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals., (© 2022 by The American Society of Hematology.)

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest of this work., (Copyright © 2022 Infante, Salmanton-García, Fernández-Cruz, Marchesi, Jaksic, Weinbergerová, Besson, Duarte, Itri, Valković, Szotkovski, Busca, Guidetti, Glenthøj, Collins, Bonuomo, Sili, Seval, Machado, Cordoba, Blennow, Abu-Zeinah, Lamure, Kulasekararaj, Falces-Romero, Cattaneo, Van Doesum, Piukovics, Omrani, Magliano, Ledoux, de Ramon, Cabirta, Verga, López-García, Da Silva, Stojanoski, Meers, Lahmer, Martín-Pérez, Dávila-Vals, Van Praet, Samarkos, Bilgin, Karlsson, Batinić, Nordlander, Schönlein, Hoenigl, Ráčil, Mladenović, Hanakova, Zambrotta, De Jonge, Adžić-Vukičević, Nunes-Rodrigues, Prezioso, Navrátil, Marchetti, Cuccaro, Calbacho, Giordano, Cornely, Hernández-Rivas and Pagano.)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality., Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020., Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases., Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases., (© 2021. The Author(s).)

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases ( n = 69; 49%), hematology ( n = 68; 48%), and others ( n = 41; 29%). BCT was performed in 57% ( n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% ( n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.

Background: Mucormycosis is an invasive fungal disease severely complicating treatment of patients with hematologic diseases. Effective therapy is represented by the combination of surgery and amphotericin B administration and early initiation of the therapy is necessary for favorable outcome. The first clinical symptoms are usually non-specific and this can lead to late therapy onset. The objective of this retrospective work was to determine the frequency, risk factors and outcome of invasive mucormycosis in pediatric hematology patients., Material and Methods: The study cohort comprised 399 patients diagnosed with hematologic diseases in the Department of Pediatric Hematology and Oncology (DPHO), University Hospital Motol, Prague between 2005 and 2010. Risk factors for the development of mucormycosis, clinical symptoms and radiology and laboratory results were retrospectively evaluated. So were the therapy used and outcomes. The findings were analyzed using Fisher's exact test., Results: During the selected period, mucormycosis was detected in 8 patients diagnosed with hematologic disease. The incidence of mucormycosis was 1.75 %. These conditions accounted for 20.6 % of all mycoses. In five patients, it was found as isolated infection; three cases were associated with other mycoses (one with candidiasis, two with aspergillosis). The most frequent underlying disease was acute leukemia; the most common risk factor was severe prolonged neutropenia (median duration 21.5 days). Three of eight patients survived mucormycosis, a mortality rate of 62.5 %. The effective therapy was amphotericin B administration in three patients (p = 0.02); in two of them, it was combined with radical surgery., Conclusion: In the cohort, the proportion of mucormycosis cases was surprisingly high when compared with other fungal diseases. Continuous surveillance of mucormycosis in the DPHO is needed. There was no significant influence of the combination of radical surgery and amphotericin B administration as compared to administration of amphotericin B alone. Nevertheless, according to the published data, we consider this approach as an optimal strategy for the management of mucormycosis at the present time.