Low platelet to lymphocyte ratio and high platelet distribution width have an inferior outcome in chronic lymphocytic leukaemia patients

Introduction.  Chronic lymphocytic leukaemia (CLL) is an incurable disease of the elderly, characterised by gradual accu­mulation of small mature B lymphocytes which escape apoptosis through inflammatory signals from the microenviron­ment. Elevated inflammatory markers are associated with very poor prognosis in different types of cancer. Therefore, we examined retrospectively the impact of platelet lymphocyte ratio (PLR) and platelet distribution width (PDW) on 180 CLL patients’ outcome. Materials and methods.  This retrospective study included 180 patients with CLL who were diagnosed and selected among cases referred to the Oncology Center Mansoura University between January 1st, 2008 and June 30th, 2016. All the relevant information was collected from the electronic medical records of the selected patients. Results.  Our results revealed that low PLR (<2.5) was more frequently observed in patients with stage C (p < 0.001), with 17p deletion (p = 0.017), and CD38 expression (p = 0.08), but not with seropositive HCV patients (p = 0.2). High PDW (≥18.5 fl) was more frequently associated with intention to treat population (p = 0.038), and CD38 expression (p = 0.068), but not with 17p deletion (p = 0.25) and seropositive HCV patients (p = 0.4). Multivariate analysis for overall survival showed that stage A and low PDW were independent factors for overall survival (p = 0.014 and 0.04 respectively), while high PLR (p = 0.05), and seronegative HCV patients (p = 0.1) lost their significance. Conclusion.  Our data showed that low PLR and high PDW were associated with poor prognostic markers. Stage C-CLL and high PDW were independent predictors of survival

Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey

COVID-19; Outcome; Prognostic factorsCOVID-19; Resultado; Factores pronósticosCOVID-19; Resultat; Factors pronòsticsBackground: 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 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.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry

Philadelphia-negative chronic myeloproliferative neoplasms; SARS-CoV-2; Essential thrombocytemiaNeoplàsies mieloproliferatives cròniques filadèlfia negatives; SARS-CoV-2; Trombocitèmia essencialNeoplasias mieloproliferativas crónicas filadelfia negativas; SARS-CoV-2; Trombocitemia esencialBackground: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19–197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58–77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357–3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363–3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363–3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: 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)

Multicentric vs. Unresectable Unicentric Castleman Disease with Active Presentation: An Orphan Rare Disease in a Young Egyptian Female Patient. A Case Report

Background: Castleman disease (CD) is a rare disorder that affects lymph nodes and has a wide range of associated symptoms. The affected lymph nodes show characteristic histological picture. Most of the unicentric Castleman disease (UCD) cases can be cured by complete surgical removal or radiotherapy, while multicentric CD (MCD) is much more complicated and have several subtypes and requires more effort to reach a precise diagnosis and management. Case presentation: A 17-years old female presented with sever fatigue and abdominal pain. Massive mediastinal lymphadenopathy was detected on radiological studies. Pathology confirmed a plasma cell variant of MCD. Autoimmune disorders, overlapping IgG4-related disease, TAFRO (Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) syndrome and other malignancies were excluded after a series of investigations. She was HIV-negative, and the human herpes virus-8 status was unknown. The final diagnosis of idiopathic MCD-not otherwise specified (iMCD-NOS) was reached. She showed a very good response to corticosteroids and monoclonal antibody course of treatment. Radiological investigations showed marked regression of the lymph node mass, and there was complete resolution of her symptoms and normalization of the hematological and biochemical parameters. Conclusion: The diagnosis and management of MCD remain very challenging, and the exclusion of infectious, autoimmune, and neoplastic disorders is necessary

Neurological presentation predicting immune thrombotic thrombocytopenic purpura outcome

Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare disorder caused by acquired autoantibodies to a disintegrin and metalloprotease with thrombospondin-1 motifs (ADAMTS-13) that normally cleaves von Willebrand factor macromolecules. It is manifested by microangiopathic hemolytic anemia, systemic microvascular thrombi formation, and subsequent end-organ ischemia (renal and neurological manifestations). Early diagnosis and management resulted in improving the survival rate. This is a retrospective study conducted to describe the clinical characteristics of patients diagnosed with iTTP, their survival, and prognostic factors affecting it. Methods: We included adult patients who met the diagnostic criteria of iTTP between 2016 and 2019. Based on PLASMIC Score for TTP, our patients ranged from 6 to 7. ADAMTS-13 testing was not done because of financial issues. Results: A total of 21 patients were included in this study. The median age of the studied patients was 30.45 years, and 81% of them were female. The most common clinical feature was fever (57.1%), followed by bleeding manifestations (52.4%), neurological manifestations (47.6%), renal impairment (42.9%), and cardiac manifestations (9.5%). There were a total of 4 deaths (19.04%). The overall survival was correlated significantly with neurological manifestations and PLASMIC scores (p = 0.02, 0.012, respectively). Conclusions: Our report reinforces that iTTP is not mandatory to be presented with classic pentad. Using PLASMIC score could help in the diagnosis and prediction of survival, and we strongly suggest that the absence of neurological manifestations  results in better overall survival. Therapeutic plasma exchange should be started as soon as possible once iTTP is suspected. Rituximab has an important role in improving treatment outcomes

Prognostic impact of lipid profile in adult Egyptian acute leukemia patients

Introduction: Acute leukemia is a malignant disorder which results from clonal proliferation of lymphoid and myeloid blast cells. Several studies have reported changes in lipid metabolism at the time of diagnosis of leukemia. Although investigators have reported decreased total cholesterol, decreased high-density lipoprotein, and elevated triglyceride (TG) in leukemic patients, there is a lack of agreement about these changes among different types of leukemia and between children and adult patients, in addition to different data about their impacts on prognosis. In this study, lipid profile has been examined at the time of diagnosis of acute leukemia in order to correlate it with response to therapy. Material and methods: This is a prospective study carried out at the Oncology Center at Mansoura University, Egypt between 2018 and 2019. Fifty patients newly diagnosed with de novo acute leukemia were included. Thirty-four patients were diagnosed with acute myeloid leukemia (AML) (68%), while 16 patients were diagnosed with acute lymphoblastic leukemia (ALL) (32%). Lipid profile and body mass index (BMI) data was obtained. Results: Overweight/obese patients showed a more statistically significant association with female patients than with male patients (p = 0.009). By comparing the lipid profile between overweight/obese patients and other patients, there was no statistically significant association. 76.7% of AML patients were overweight or obese (p = 0.015), and 81.3% of ALL patients showed hypertriglyceridemia (p = 0.014). There was no statistically significant association between lipid profile and complete response (CR) rate; however, there was a marginally significant association between non-CR rate and overweight and obese patients (p = 0.051). In addition, there was no impact of BMI or lipid profile on overall survival among acute leukemia patients. Conclusions: Female, and acute myeloid leukemia, patients were more commonly associated with overweight and obesity, and high TG level was found to be associated with acute lymphoid leukemia. Changes in lipid profile showed no impact on complete response rate or on overall survival in acute leukemia patients

Correction: Need for ICU and outcome of critically ill patients with COVID-19 and haematological malignancies: results from the EPICOVIDEHA survey (Infection, (2024), 52, 3, (1125-1141), 10.1007/s15010-023-02169-7)

Acknowledgements Members of the EPICOVIDEHA registry: Joseph Meletiadis, Florian Reizine, Jan Novák, Summiya Nizamuddin, Roberta Di Blasi, Alexandra Serris, Pavel Jindra, Sylvain Lamure, François Danion, Maria Chiara Tisi, Mario Virgilio Papa, Nurettin Erben, ľuboš DrgoňA, Nathan C. Bahr, Murtadha Al-Khabori, Ayten Shirinova, Jörg Schubert, Lisset Lorenzo De La Peña, José-Ángel Hernández-Rivas, Elena Busch, Josip Batinić, Giuseppe Sapienza, Mohammad Reza Salehi, Reham Abdelaziz Khedr, Nina Khanna, Baerbel Hoell-Neugebauer, Ana Groh, Eleni Gavriilaki, Rita Fazzi, Rémy Duléry, Roberta Della Pepa, Mario Delia, Nicola Coppola, Maria Calbacho, Darko Antić, Hossein Zarrinfer, Ayel Yahia, Vivien Wai-Man, Ana Torres-TIenza, Alina Daniela Tanasa, Andrés Soto-Silva, Laura Serrano, Enrico Schalk, Ikhwan Rinaldi, Gaëtan Plantefeve, Monica Piedimonte, Maria Enza Mitra, Carolina Miranda-Castillo, Jorge Loureiro-Amigo, Ira Lacej, Martin Kolditz, María-Josefa Jiménez-Lorenzo, Guillemette Fouquet, Omar-Francisco Coronel-Ayala, Mathias Brehon, Panagiotis Tsirigotis, Anastasia Antoniadou, Gina Varricchio, Maria Vehreschild, Agostino Tafuri, José-María Ribera-Santa Susana, Joyce Marques De Almeida, María Fernández-Galán, Avinash Aujayeb, Athanasios Tragiannidis, Malgorzata Mikulska, Sein Win, Elizabeth De Kort, Hans-Beier Ommen, Donald C. Vinh, Hans Martin Orth, Sandra Malak, Przemyslaw Zdziarski, Modar Saleh, Chi Shan Kho, Fabio Guolo, M. Mansour Ceesay, Christopher H. Heath, Sergey Gerasymchuk, Monica Fung, Maximilian Desole, Erik De Cabo, Tania Cushion, Fazle Rabbi Chowdhury, Louis Yi Ann Chai, Fevzi Altuntaş, Charlotte Flasshove. The original article has been updated.</p

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies:a report from the EPICOVIDEHA registry

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).</p

Decoding the historical tale:COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.</p