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

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

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&nbsp;=&nbsp;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)

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

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. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% 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) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR?=?1.022, 95%CI 1.007?1.038 and OR?=?1.025, 95%CI 1.001?1.051, respectively), while thromboprophylaxis use was protective (OR?=?0.199, 95%CI 0.061?0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR?=?1.062, 95%CI 1.017-1.109 and OR?=?2.438, 95%CI 1.023-5.813, 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

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and &gt;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 haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological 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.tThe 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 leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts