Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE.

The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.

Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.

Background: The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group).

Objectives: To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis.

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.

Background: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.

Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial.

Purpose: Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities.

Patients And Methods: ALPINE (ClinicalTrials.

Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry.

Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN).

A phase 1b/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia.

A phase 1b/2, three-month study of marstacimab, a human monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), was conducted in participants with haemophilia A or B, with or without inhibitors. Participants assigned to four cohorts received escalating weekly doses based on inhibitor status (without inhibitors: 300 mg, a single 300-mg loading dose with subsequent 150-mg doses, or 450 mg; with inhibitors: 300 mg). Safety outcomes were treatment-emergent adverse events (TEAEs), injection site reactions, clinical and laboratory parameter changes.

Strength training program for an athlete with hemophilia A and an inhibitor while taking a new prophylactic drug treatment: a case report.

Background: Currently, patients with hemophilia and inhibitor are being offered therapy, including a tissue factor pathway inhibitor (TFPI). The new prophylactic drug treatment may allow for new opportunities for other interventions and overall improvement in quality of life. This case report assessed the safety and effects of a strength training program in a patient with an inhibitor on a specific new study drug.

Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial.

Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655 ) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients with AdvSM (n = 62).

Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis.

In April 2017 midostaurin was approved by the US Food and Drug Administration for the treatment of patients with aggressive systemic mastocytosis (ASM). So far, very limited real world data on its efficacy is available. Thirteen patients aged from 48 to 79 years, who received midostaurin in the early access program, were included in the study.

Excessive amount and activity of μ-calpain affects apoptotic machinery in chronic B-cell leukemia cells and influences the course of the disease.

B-cell Chronic Lymphocytic Leukemia (B-CLL) is the most common hematological disorder among middle-aged/elderly people in the Western countries. We have shown earlier that B-CLL cells exhibit elevated total amount and available activity of µ-calpain, belonging to a family of ubiquitous, strongly Ca-dependent proteases, involved in the control of proliferation and apoptosis. In this study we attempted to estimate a potential clinical value of μ-calpain in relation to B-CLL clinical staging in patients with extremely high lymphocytosis and studied the molecular mechanisms associating calpain activity with clinical progress of the disease.

COVID-19 - Toward a comprehensive understanding of the disease.

The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic.

Genetic and clinical characterization of congenital fibrinogen disorders in Polish patients: Identification of three novel fibrinogen gamma chain mutations.

Introduction: Congenital fibrinogen disorders are poorly explored in Slavic populations. The aim of this study was to characterize the genetic background and clinical manifestations of fibrinogen disorders in the Polish case series.

Materials And Methods: In 27 unrelated patients (mean [SD] age, 30.

Acquired von Willebrand Syndrome.

Acquired von Willebrand syndrome is a rare hemorrhagic diathesis, with clinical symptoms similar to those associated with the inherited form von Willebrand disease. This syndrome is characterized by a lack of previous bleeding symptoms, negative familial history, and occurrence in a relatively older age. Most commonly, acquired von Willebrand syndrome develops in the course of other conditions, such as lymphoproliferative, myeloproliferative, cardiovascular and autoimmune disorders; additionally, it can be associated with some non-hematological malignancies and use of certain prescription drugs.

Are myelodysplastic syndromes underdiagnosed in Poland? A report by the Polish Adult Leukaemia Group.

Objectives: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland.

Methods: Twenty-one haematological centres participated in the study.

Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry.

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients.

Acquired von Willebrand Syndrome During the Course of Myelofibrosis: Analysis of 32 Cases.

Background: Identification of patients with myelofibrosis being at increased risk of acquired von Willebrand syndrome (avWS) would likely facilitate individualization of treatment and improve its outcomes.

Objectives: To determine the prevalence of avWS in patients with myelofibrosis, and to verify if individuals with and without this bleeding disorder differ in terms of their baseline clinical parameters.

Material And Methods: The study included 32 consecutive patients with myelofibrosis.

Prevalence of acquired von Willebrand syndrome during essential thrombocythemia: a retrospective analysis of 170 consecutive patients.

Introduction: The identification of patients with essential thrombocythemia (ET) who are at increased risk of acquired von Willebrand syndrome (AVWS) would likely facilitate individualization of treatment and improve its outcomes.

Objectives: The aim of the study was to determine the prevalence of AVWS in patients with ET and to verify whether individuals with and without this bleeding disorder differ in terms of their baseline clinical parameters.

Patients And Methods: The study included 170 consecutive patients with ET.

Factors predisposing to acquired von Willebrand syndrome during the course of polycythemia vera - retrospective analysis of 142 consecutive cases.

Introduction: The aim of this study was to verify if PV patients with and without avWS differ in terms of their baseline clinical parameters.

Material And Methods: The study included 142 consecutive patients with PV. avWS was diagnosed on the basis of abnormally low levels of von Willebrand factor and other routine tests.

Polish experience of lenalidomide in the treatment of lower risk myelodysplastic syndrome with isolated del(5q).

Background: Lenalidomide has been approved for the treatment of lower-risk myelodysplastic syndrome (MDS) with 5q deletion (del(5q)). We present for the first time a retrospective analysis of low-risk MDS with isolated del5q treated with lenalidomide, outside the clinical trials.

Methods: 36 red blood cell (RBC) transfusion-dependent patients have been included in the study.

Assessment of platelet function in endogenous hypercortisolism.

Introduction: It is commonly known that glucocorticoids exert a significant effect on haemostasis. Studies that have analysed the plasmatic coagulation system and fibrinolysis parameters in hypercortisolaemic patients are abundant. Platelet function, which plays a vital role in primary haemostasis, is much less clear in this context.

Demographic, Hematologic, and Clinical Features of Myelodysplastic Syndrome Patients: Results from the First Polish Myelodysplastic Syndrome Registry.

Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes.