Showing papers in "European Journal of Haematology in 2022"
TL;DR: Relapse in two out of the four patients was refractory to CsA/eltrombopag, favoring IST with hATG/CsA or BMT, respectively, and all relapsed patients were vaccinated with the mRNA‐based vaccine Comirnaty®.
Abstract: COVID‐19 is a potential life‐threatening viral disease caused by SARS‐CoV‐2 and was declared a pandemic by the WHO in March 2020. mRNA‐based SARS‐CoV‐2 vaccines are routinely recommended in immune‐compromised patients, including patients with AA, as these patients are at increased risk of contracting COVID‐19 and developing a more severe course of disease. Between March 2021 and November 2021 relapse of AA occurred in four (age [median]: 53 years, range 30–84 years) out of 135 patients currently registered at our department and two de novo cases of AA in temporal context to vaccination against SARS‐CoV‐2, were documented. Median time after first COVID‐19 vaccination and relapse of AA was 77 days. All relapsed patients were vaccinated with the mRNA‐based vaccine Comirnaty®. Relapse in two out of the four patients was refractory to CsA/eltrombopag, favoring IST with hATG/CsA or BMT, respectively. Our observations should prompt clinicians to take vaccine‐induced relapse of AA or de novo AA after SARS‐CoV‐2 vaccination into account. Furthermore, careful clinical monitoring and vigilance for signs or symptoms that may indicate relapse of AA (e.g., bleeding complications) are indicated.
14 citations
TL;DR: In this paper , a single-center chart review was conducted to quantify the hematologic response and validated reported reported outcomes with voxelotor treatment, which validated reported outcomes.
Abstract: The aim of this single‐center chart review was to quantify the hematologic response and validated reported outcomes with voxelotor treatment.
11 citations
TL;DR: In this article , the authors assessed clinical and laboratory parameters in 61 patients with underlying hematologic conditions with a SARS-CoV2 omicron variant infection confirmed by nucleic acid amplification testing.
Abstract: Patients with hematologic disease are at high risk of morbidity and mortality from COVID-19 due to disease-inherent and therapy-related immunodeficiency. Whether infection with the SARS-CoV2 omicron variant leads to attenuated disease severity in these patients is currently unknown.We assessed clinical and laboratory parameters in 61 patients with underlying hematologic conditions with a SARS-CoV2 omicron variant infection confirmed by nucleic acid amplification testing.Fifty patients reported symptoms of COVID-19, most commonly fatigue (37 patients, 60.66%) and cough (32 patients, 52.46%). 39.34% of patients reported fever. Dyspnea was reported by 10 patients and 7 patients (11.48%) required oxygen therapy. Anosmia and ageusia were relatively rare, occurring in less than 10% of patients. Severity of SARS-CoV2 infection could be assessed in 60 patients. Five cases of critical illness leading to ICU admission occurred during the observation period. Overall mortality was 9.84% in this patient cohort, with heterogeneous causes of death. The majority of omicron-infected hematologic patients experienced mild symptoms or remained asymptomatic.In this study, symptoms of COVID-19 tended to be milder than described for previous SARS-CoV2 variants. However, the extent to which attenuated severity of omicron-variant SARS-CoV2 infection is caused by altered viral pathogenicity or pre-existing host immunity cannot be inferred from our data and should be investigated in larger prospective studies.
11 citations
TL;DR: This study aims to describe the results of both studies from 27 weeks to 2 years of treatment in complement inhibitor‐naïve and complement inhibitors‐experienced patients with paroxysmal nocturnal hemoglobinuria.
Abstract: The complement component 5 (C5) inhibitor ravulizumab demonstrated non‐inferiority to eculizumab following 26 weeks of treatment in complement inhibitor‐naïve and complement inhibitor‐experienced patients with paroxysmal nocturnal hemoglobinuria (PNH; studies 301 and 302, respectively). This study aims to describe the results of both studies from 27 weeks to 2 years.
10 citations
TL;DR: It is demonstrated that fourth SARS-CoV-2 vaccination improves serologic response in patients with CLL to a lesser extent than healthy controls and induces functional T-cell response.
Abstract: We assessed the humoral and cellular response to the fourth BNT162b2 mRNA COVID‐19 vaccine dose in patients with CLL. A total of 67 patients with CLL and 85 age matched controls tested for serologic response and pseudo‐neutralization assay. We also tested the functional T‐cell response by interferon gamma (IFNγ) to spike protein in 26 patients. Two weeks after the fourth vaccine antibody serologic response was evident in 37 (55.2%) patients with CLL, 20 /22 (91%) of treatment naïve, and 9/32 (28%) patients with ongoing therapy, compared with 100% serologic response in age matched controls. The antibody titer increased by 10‐fold in patients with CLL, however, still 88‐folds lower than age matched controls. Predictors of better chances of post fourth vaccination serologic response were previous positive serologies after second, third, and pre‐fourth vaccination, neutralizing assay, and treatment naïve patients. T‐cell response improved from 42.3% before the fourth vaccine to 84.6% 2 weeks afterwards. During the time period of 3 months after the fourth vaccination, 14 patients (21%) developed COVID‐19 infection, all recovered uneventfully. Our data demonstrate that fourth SARS‐CoV‐2 vaccination improves serologic response in patients with CLL to a lesser extent than healthy controls and induces functional T‐cell response.
9 citations
TL;DR: There is increasing data suggesting that newer intravenous formulations are safe and effective in the second and third trimesters and should be strongly considered in pregnant individuals without optimal response to oral iron repletion.
Abstract: Iron deficiency and/or iron deficiency anemia (IDA) complicate nearly 50% of pregnancies globally, negatively impacting both maternal and fetal outcomes. Iron deficiency can cause a range of symptoms that range from aggravating to debilitating including fatigue, poor quality of life, pagophagia, and restless leg syndrome. Iron deficiency and IDA are also associated with maternal complications including preterm labor, increased rates of cesarean delivery, postpartum hemorrhage, and maternal death. Fetal complications include increased rates of low birth weight and small for gestational age newborns. Prenatal maternal anemia has also been associated with autism spectrum disorders in the neonate, although causation is not established. Deficiency in the newborn is associated with compromised memory, processing, and bonding, with some of these deficits persisting into adulthood. Despite the prevalence and consequences associated with iron deficiency in pregnancy, data show that it is routinely undertreated. Due to the physiologic changes of pregnancy, all pregnant individuals should receive oral iron supplementation. However, the bioavailability of oral iron is poor and it is often ineffective at preventing and treating iron deficiency. Likewise, it frequently causes gastrointestinal symptoms that can worsen the quality of life in pregnancy. Intravenous iron formulations administered in a single or multiple dose series are now available. There is increasing data suggesting that newer intravenous formulations are safe and effective in the second and third trimesters and should be strongly considered in pregnant individuals without optimal response to oral iron repletion.
9 citations
TL;DR: In this paper , the authors analyzed 21 patients with relapsed/refractory DLBCL to determine real-life efficacy and safety of the Pola-BR regimen in the NiHiL project (NCT03199066).
Abstract: Polatuzumab vedotin with bendamustine and rituximab (Pola-BR) was approved for treatment of transplant-ineligible patients with relapsed/refractory DLBCL (R/R DLBCL). However, the number of patients treated in the GO29365 trial including the extension cohort was limited, and more data evaluating the efficacy of this treatment regimen is needed.We analyzed 21 patients with R/R DLBCL to determine real-life efficacy and safety of Pola-BR regimen. Data of all patients entered the database of the NiHiL project (NCT03199066).Median overall survival was 8.7 months, and progression-free survival 3.8 months. The overall response rate was 33%. Grade 3-4 neutropenia was detected in 29%, thrombocytopenia in 38%, anemia in 19%, infections in 24% cases, and peripheral neuropathy in 5%. Discontinuation of treatment was caused by progression in 50%, adverse events in 31%, and intended bridging to CAR-T therapy in 19%.Although the outcome of patients is worse than in GO29365 trial, the use of Pola-BR regimen in the real world demonstrates tolerable toxicity profile and efficacy in transplant-ineligible patients with R/R DLBCL. Moreover, this regimen might represent a perspective option as a bridge to CAR-T therapy.
8 citations
TL;DR: In this article , the authors examined the available evidence regarding the use of immune checkpoint inhibitors (ICIs) and thrombosis, and described the potential mechanisms by which ICIs might lead to throm bophilia given the overlap between the immune system, coagulation cascade, and platelet activation.
Abstract: Malignancy has long been implicated with hypercoagulability, leading to an increased rate of both venous and arterial thromboembolic events (VTE and ATE). Immunotherapy has established itself as a cornerstone of modern cancer therapy by promoting antitumor immune responses, though there have been some suggestions that immune-related adverse events could include increased rates of VTE and ATE. In this review, we examine the available evidence regarding the use of immune checkpoint inhibitors (ICIs) and thrombosis. First, we describe the potential mechanisms by which ICIs might lead to thrombophilia given the overlap between the immune system, coagulation cascade, and platelet adhesion and activation. In addition, while there are some preclinical data evaluating immunotherapy-associated ATEs in animal models, there is a paucity of evidence exploring potential mechanism of VTEs in ICIs. Second, we review the incidence of ATE and VTE in patients receiving ICIs in the published literature. Finally, we discuss current limitations in understanding, areas of conflicting evidence, and approaches to further investigation.
7 citations
TL;DR: The role of direct oral anticoagulants among patients with antiphospholipid syndrome (APLS) remains unclear, and it remains unknown whether DOACs may be appropriate for lower‐risk patients such as those with single‐positive APLS.
Abstract: The role of direct oral anticoagulants (DOACs) among patients with antiphospholipid syndrome (APLS) remains unclear. Warfarin has been shown to be superior to DOACs among high‐risk APLS patients (particularly those with triple‐positive APLS). However, it remains unknown whether DOACs may be appropriate for lower‐risk patients such as those with single‐positive APLS.
7 citations
TL;DR:
Abstract: Many patients with plasma cell disorder (PCD) on active treatment with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) require hospitalization, with an increased mortality rate over healthy adults. The FDA approved two mRNA vaccines against SARS‐CoV‐2: BNT162b2 and mRNA‐1273. To assess the efficacy of vaccination in patients with PCD, retrospectively, we identified all patients on active treatment. A total of 149 patients were included. Neutralizing antibodies (NAbs) levels against SARS‐CoV‐2 adequate, intermediate, and no response were observed in 42%, 32%, and 26%, respectively. Low NAbs were seen in patients on daratumumab combinations or anti‐BCMA therapy, low lymphocytes, and low IgG levels. Twenty‐three (15%) patients have SARS CoV‐2, while 8% required hospitalization, majority of these patients had intermediate or no response based on NAbs levels. Therefore, checking NAbs may be clinically helpful in identifying patients' responses. Further prospective studies should ascertain the value of a third vaccine dose in this population.
7 citations
TL;DR: To establish the prevalence of pain and functional disability in Irish adults with moderate and severe haemophilia, and to examine demographic and lifestyle influences.
Abstract: To establish the prevalence of pain and functional disability in Irish adults with moderate and severe haemophilia, and to examine demographic and lifestyle influences.
TL;DR: Autoimmune hemolytic anemia is considered a chronic disease, with an overall good prognosis, however, recent reports indicate pre‐mature mortality, and causes of death have not been evaluated previously.
Abstract: Autoimmune hemolytic anemia (AIHA) is considered a chronic disease, with an overall good prognosis. However, recent reports indicate pre‐mature mortality. Causes of death have not been evaluated previously.
TL;DR: A case of a 54‐year‐old man with follicular lymphoma diagnosed with PML after being treated with anti‐CD20 monoclonal antibody‐based regimens for several years is presented, due to the lack of effective treatment choices for PML.
Abstract: Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system (CNS) caused by the reactivation of JC polyomavirus in the CNS. We present a case of a 54‐year‐old man with follicular lymphoma diagnosed with PML after being treated with anti‐CD20 monoclonal antibody‐based regimens for several years. Due to the lack of effective treatment choices for PML, the patient was treated with nivolumab, based on recent reports, but succumbed to his disease a few months after diagnosis. In this paper, we focus on reviewing the literature of PML cases correlated with newer agents used in hematology, possible factors affecting disease prognosis, as well as the available data on upcoming therapeutic options for patients with PML. Though newer promising treatments such as anti‐PD1 monoclonal antibodies arise, a definitive treatment option is yet to be found. Vigilance, early detection, and prompt intervention play a crucial role in the prognosis of PML in patients with hematological malignancies.
TL;DR: In this paper , a prespecified interim analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d; Isa-Kd) significantly improved progression-free survival (PFS) versus Kd in patients with relapsed multiple myeloma.
Abstract: Introduction The presence of high-risk chromosomal abnormalities [t(4;14), del(17p), and t(14;16)] has been linked with inferior outcomes in patients with multiple myeloma (MM). A prespecified interim analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d; Isa-Kd) significantly improved progression-free survival (PFS) versus Kd in patients with relapsed MM. This prespecified subgroup analysis of IKEMA examined efficacy and safety in patients with high-risk cytogenetics. Methods High-risk cytogenetics was assessed by central laboratory and patients were classified as high risk if abnormalities were present in ≥1 of the following: del(17p): 50% cutoff; t(4;14), and/or t(14;16): 30% cutoff. Results Of the randomized patients, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk chromosomal abnormality. A PFS benefit was seen in favor of Isa-Kd for patients with standard-risk (HR 0.440; 95% CI 0.266–0.728) and high-risk cytogenetics (HR 0.724; 95% CI 0.361–1.451). Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd (85.7%) versus Kd (63.3%) in patients with high-risk cytogenetics; however, the incidence of serious TEAEs (64.3% vs. 66.7%) was similar. Conclusions Isa-Kd is a new treatment option for the difficult-to-treat subgroup of patients with relapsed MM and high-risk cytogenetics.
TL;DR: Adult primary immune thrombocytopenia (ITP) is a rare bleeding disorder of unknown cause and its incidence and trend over time were acquired for England.
Abstract: Adult primary immune thrombocytopenia (ITP) is a rare bleeding disorder of unknown cause. Recent estimates of its incidence and trend over time were acquired for England.
TL;DR: Early‐stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up, and needs further study to establish a causative mechanism and determine a single treatment strategy.
Abstract: Early‐stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow‐up.
TL;DR: In this paper , the authors review the pathophysiology of iron absorption and current evidence for various preparations of oral iron and highlight opportunities for further study to advance the care of individuals affected by iron deficiency.
Abstract: Iron deficiency is the most common nutrient deficiency in the world, affecting over twenty percent of premenopausal women worldwide. Oral iron supplementation is often the first line treatment for the acute and chronic management of iron deficiency due to its ease and accessibility. However, there is no consensus on the optimal formulation or dosing strategy, or which patients should be preferentially treated with intravenous iron. Management of iron deficiency is complicated by the hepcidin-ferroportin iron regulatory pathway, which has evolved to prevent iron overload and thereby creates an inherent limit on gastrointestinal iron uptake and efficacy of oral iron. Unabsorbed iron propagates many of the side effects that complicate oral iron use including dyspepsia and constipation, all of which can thus be exacerbated by excessive oral iron doses. Daily low dose and every other day dosing protocols have attempted to bypass this physiologic bottleneck to allow for effective absorption and limit side effects; however, this approach has still resulted in low fractional iron absorption. In the following manuscript, we review the pathophysiology of iron absorption and current evidence for various preparations of oral iron. Lastly, we highlight opportunities for further study to advance the care of individuals affected by iron deficiency.
TL;DR: Data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality‐of‐life benefits.
Abstract: Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty‐nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.2%) patients received the first cycle as inpatients, whereas 40/59 (67.8%) patients were treated in the outpatient setting. No significant differences were observed with regard to incidence of adverse events (AEs), including tumor lysis syndrome (TLS), and the 30‐day and 60‐day mortality was comparable. Notably, an infectious prophylaxis inspired to that adopted during intensive chemotherapy resulted in a low infection rate with a reduced bacterial infections incidence in out‐ versus hospitalized patients (p < .0001). The overall time of hospitalization was significantly shorter in patients who received a total outpatient treatment as compared to those who received the first cycle as inpatients (5.9 vs. 39.7 days, p < .0001). Despite the adopted differences in treatment management, the efficacy was similar. These data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality‐of‐life benefits.
TL;DR: To assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)‐treated patients with PNH, a large number of patients treated with C5i have PNH.
Abstract: To assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)‐treated patients with PNH.
TL;DR: Recent advances in the understanding of pathobiology, clinical features, investigative work‐up, and management of VITT are reviewed.
Abstract: In late February 2021, a prothrombotic syndrome was encountered for the first time in some of the recipients of ChAdOx1 CoV‐19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India). Since the hallmark of this syndrome is the development of thrombocytopenia and/or thrombosis between 4 and 42 days after receiving a COVID‐19 vaccine, it was named vaccine‐induced immune thrombotic thrombocytopenia (VITT). Other names include “vaccine‐induced prothrombotic immune thrombocytopenia” and “thrombosis with thrombocytopenia syndrome” by the Centers for Disease Control and the Food and Drug Administration (FDA). VITT appears similar to heparin‐induced thrombocytopenia in that “platelet activating” autoantibodies are produced in both these conditions due to prior exposure of COVID‐19 vaccine and heparin respectively, in turn causing thrombotic complications and consumptive thrombocytopenia. In this article, recent advances in the understanding of pathobiology, clinical features, investigative work‐up, and management of VITT are reviewed.
TL;DR: This work addresses the involvement of TR3−56 cells in MDS pathogenesis/progression and describes the TR3+56 T cell subset, characterised by the co‐expression of CD3 and CD56, as a novel immune‐regulatory population able to modulate cytotoxic functions.
Abstract: Emergence of dysplastic haematopoietic precursor/s, cytopenia and variable leukaemia risk characterise myelodysplastic syndromes (MDS). Impaired immune‐regulation, preferentially affecting cytotoxic T cells (CTL), has been largely observed in MDS. Recently, we described the TR3−56 T cell subset, characterised by the co‐expression of CD3 and CD56, as a novel immune‐regulatory population, able to modulate cytotoxic functions. Here, we address the involvement of TR3−56 cells in MDS pathogenesis/progression.
TL;DR: Pixantrone is a novel aza‐anthracenedione with antineoplastic activity, currently approved for multiply relapsed/refractory diffuse large B‐cell lymphoma (DLBCL), even if real‐life data are limited.
Abstract: Pixantrone is a novel aza‐anthracenedione with antineoplastic activity, currently approved for multiply relapsed/refractory diffuse large B‐cell lymphoma (DLBCL), even if real‐life data are limited.
TL;DR: This retrospective chart review examined real‐world healthcare resource utilization (HRU) in patients with AML ineligible for intensive therapy who received first‐line systemic therapy or best supportive care (BSC) and found no significant differences between the two categories.
Abstract: This retrospective chart review examined real‐world healthcare resource utilization (HRU) in patients with AML ineligible for intensive therapy who received first‐line systemic therapy or best supportive care (BSC).
TL;DR: To conduct a systematic review of tranexamic acid (TXA) and the risk of renal failure from urinary clots in adult patients with hematuria.
Abstract: To conduct a systematic review of tranexamic acid (TXA) and the risk of renal failure from urinary clots in adult patients with hematuria.
TL;DR: The composite endpoint provided a single and simultaneous measurement of overall benefit for patients receiving treatment for PNH and its use in health technology assessments should be evaluated.
Abstract: This study developed and explored a novel composite endpoint to assess the overall impact that treatment can have on patients living with paroxysmal nocturnal hemoglobinuria (PNH). Candidate composite endpoint variables were selected by a group of experts and included: lactate dehydrogenase levels as a measure of intravascular hemolysis; complete terminal complement inhibition; absence of major adverse vascular events, including thrombosis; absence of any adverse events leading to death or discontinuation of study treatment; transfusion avoidance; and improvements in fatigue‐related quality of life as determined by the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue score. From these variables, a novel composite endpoint was constructed and explored using data collected in the ravulizumab PNH Study 301 (NCT02946463). Thresholds were defined and reported for each candidate variable. Five of the six candidate variables were included in the final composite endpoint; the FACIT‐Fatigue score was excluded. Composite endpoint criterion was defined as patients meeting all five selected individual component thresholds. All patients in the ravulizumab arm achieved complete terminal complement inhibition and a reduction in lactate dehydrogenase levels; 51.2% and 41.3% of patients in the ravulizumab arm and eculizumab arm, respectively, achieved all composite endpoint component thresholds (treatment difference: 9.4%; 95% confidence interval: −3.0, 21.5). The composite endpoint provided a single and simultaneous measurement of overall benefit for patients receiving treatment for PNH. Use of the composite endpoint in future PNH research is recommended to determine clinical benefit, and its use in health technology assessments should be evaluated.
TL;DR: A retrospective analysis of postvaccination antibody levels and blood counts in patients with aplastic anemia and the development of SARSCoV2specific vaccinations found that all patients developed detectable antibody titers with a median of 553 BAU/ml within the first 6 months after the second vaccination.
Abstract: Letter to the editor, In 2020, the SARSCoV2 virus spread all over the world also affecting patients with hematologic diseases.1 Patients with aplastic anemia (AA) were thought to be at particular risk for severe or fatal courses of COVID19 due to cytopenias caused by the underlying disease as well as through their immunosuppressive treatment regimens.1,2 Consequently, the European Society for Blood and Marrow Transplantation (EBMT) and the Severe Aplastic Anemia Working Party (SAAWP) recommended to carefully consider the timing of initiation of immunosuppressive treatment (IST) and/or allogeneic stem cell transplantation (ASCT) to prevent AA patients from avoidable cytopenias and hospitalization.3 One milestone in the control of the pandemic was the development of SARSCoV2specific vaccinations. For mRNA or vectorbased types of vaccines, it has been shown that levels of neutralizing antibodies against the spike protein of SARSCoV2 correlate with the risk of infection and hospitalization in healthy individuals.4 As antithymocyte globuline (ATG) and cyclosporine A (CSA) are known to impair Tand Bcellmediated immune responses, it is presumed that immune responses to SARSCoV2 vaccination of AA patients under IST may be inappropriate, especially in the first months after ATG/CSA initiation.3,5 Up to now, no data have been published about antibody titers following vaccination of patients with AA. We initiated a retrospective analysis of postvaccination antibody levels and blood counts in patients with AA or AA/PNH overlap syndrome. Sixteen patients (8 female/8 male, median age 57.5 years, range 24– 69 years) were identified with sufficient data within the Aachen Registry for Telomeropathies and Aplastic Syndromes.6 Written informed consent for the registry was obtained according to the approval by the local ethic committee EK (332/20). All patients are currently undergoing immunosuppressive treatment including ATG and CSA and/or additional treatments with Eltrombopag or C5complement inhibitors at the University Hospital of RWTH Aachen. All patients treated with ATG received horse ATG (ATGAM®). Details about treatments including time intervals between diagnosis, ATG application, and first vaccination are shown in Table 1. All 16 patients received at least two vaccinations and all antibody titers against the SARSCoV2 spike protein were measured within the first 7 months after the second vaccination. Measurement of antibody titers against the nucleoprotein (N) of SARSCoV2 was not carried out. Eightyeight percent (14/16) of the patients received BTN162B2 (Pfizer/BioNTech), 6% (1/16) mRNA1273 (Moderna), and 6% (1/16) ChAdOx1 (AstraZeneca), respectively. One quarter (4/16) received a third vaccination with BTN162B2 (Pfizer/Biontech). In our cohort, no symptomatic COVID19 infection after vaccination was observed. Concerning asymptomatic SARSCoV2 infections, the patients did not report positive results for SARSCoV2specific PCR or rapid antigen test during followup. Analysis of the vaccinationinduced antibody levels against the SARSCoV2 spike protein showed that all patients developed detectable antibody titers with a median of 553 BAU/ml (range 168– 1040 BAU/ml) within the first 6 months after the second vaccination. In spite of the small number of patients, we observed a tendency to lower antibody levels in our two patients who received two vaccinations within the first 2 months after ATG treatment (#9: 168 BAU/ml; #1: 406 BAU/ml 2 months after second vaccination). We did not observe further correlations of treatment modalities and antibody levels. Since antibody levels against the SARSCoV2 spike protein are known to rapidly decrease within the first weeks after second vaccinations in healthy individuals,7 we stratified our patients antibody titers in a crosssectional approach according to the time after second vaccination. Here, we found a continuous decline in antibody levels from a median of 848 BAU/ml (range 176– 1040 BAU/ml) after the 1st month to 410 BAU/ml (range 168– 1040 BAU/ml) in the 2nd month and to 367 BAU/ml (range 223– 936 BAU/ml) after 3 to 6 months after the second vaccination (Figure 1A). Antibody levels were comparable to those recently published in a large cohort of health care workers with mean antibody levels of 760, 688, and 501 BAU/ml after 1, 2, and 3 months, respectively.7 Our observation of declining antibody levels was further confirmed in six patients where individual followup measurements of the vaccination levels were available. Here, all patients except for one (patient #10, Table 1) showed declining antibody levels over time (Figure 1B). Of note, third vaccinations resulted in adequate and rapid increase in the antibody levels >1040 BAU/ml in four of our patients with available followup data (Figure 1C). Recent reports showed a possible relationship between vaccination and relapse or de novo AA.8,9 All patients within this cohort, showed stable blood counts in all three linages after any of
TL;DR: This study indicates that apixaban and rivaroxaban are not associated with an increase in VTE recurrence in the morbidly obese; however, bleeding rates were slightly higher in the rivroxaban group compared to the apxaban group.
Abstract: INTRODUCTION
Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists in the treatment of venous thromboembolism and as prophylaxis against recurrence. However, there is inadequate data to support the safety and efficacy of DOACs in the morbidly obese, and warfarin treatment is currently recommended by the International Society of Hemostasis and Thrombosis for this population.
MATERIALS AND METHODS
We performed a retrospective review of outcomes in 499 patients with BMI ≥ 40 kg/m2 admitted from January 2013 to January 2020 with acute venous thromboembolism (VTE) and treated with either rivaroxaban (n=296) or apixaban (n=203).
RESULTS
There were 38 (7.6%) bleeding and clotting events within 60 days of the initiation of DOACs, of which 35 (7.0%) were bleeding events and 3 (0.6%) were clotting events. Patients treated with rivaroxaban had more bleeding episodes (23, 7.8% vs. 12, 5.9%) and higher mortality (21, 7.1% vs. 13, 6.4%) compared with those treated with apixaban; however, these differences were not statistically significant (p=.427 and p=.764, respectively). Most of the bleeding occurred in the genitourinary and gastrointestinal tracts.
CONCLUSIONS
Our study indicates that apixaban and rivaroxaban are not associated with an increase in VTE recurrence in the morbidly obese; however, bleeding rates were slightly higher in the rivaroxaban group compared to the apixaban group.
TL;DR: The HLH‐2004 criteria are commonly used diagnostic criteria, whereas HScore was recently developed for reactive HLH, and it is shown that the former is more accurate than the latter.
Abstract: Timely diagnosis of hemophagocytic lymphohistiocytosis (HLH) is critical and relies on clinical judgment. The HLH‐2004 criteria are commonly used diagnostic criteria, whereas HScore was recently developed for reactive HLH.
TL;DR: Long-term results are particularly favorable to ibrutinib (alone or in combination) and discourage further use of chlorambucil, and the multi-treatment Kaplan-Meier graph summarized the available evidence in comparative terms.
Abstract: In chronic lymphocytic leukemia, growing evidence has accumulated about long‐term outcomes of first‐line treatments. Our objective was to perform indirect comparisons across first‐line treatments.
TL;DR: A review of current and emerging therapies for multiple myeloma (MM) can be found in this article , where the authors present a comparison of the most effective and emerging treatments.
Abstract: This paper reviews current and emerging therapies for multiple myeloma (MM).