Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

Hematopoietic and leukemic stem cells homeostasis: the role of bone marrow niche.

The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche.

Management of infections for patient treated with ibrutinib in clinical practice.

Ibrutinib, a highly effective inhibitor of the Bruton tyrosine kinase, has significantly transformed the therapeutic approach in chronic lymphocytic leukemia (CLL). Despite these advancements, the disease continues to be characterized by immune dysfunction and increased susceptibility to infections, with mortality rates from infections showing no significant improvement over the past few decades. Therefore, timely prevention, recognition, and treatment of infections remains an important aspect of the standard management of a patient with CLL.

The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria.

Treatment options for acute myeloid leukemia patients aged <60 years.

Treatment of acute myeloid leukemia (AML) has changed over the last few years, after the discovery of new drugs selectively targeting AML blasts. Although 3/7 remains the standard of care for most AML patients, several new targeted agents (such as FLT3 inhibitors, CPX-351, gemtuzumab ozogamicin, BCL-2 inhibitor, and oral azacitidine), either as single agents or combined with standard chemotherapy, are approaching clinical practice, starting a new era in AML management. Moreover, emerging evidence has demonstrated that high-risk AML patients might benefit from both allogeneic stem cell transplant and maintenance therapy, providing new opportunities, as well as new challenges, for treating clinicians.

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.

Real-life efficacy and safety of idelalisib in 55 double-refractory follicular lymphoma patients.

Idelalisib, a reversible inhibitor of PI3Kδ (phosphoinositide-3 kinase delta), showed remarkable activity in the phase II DELTA trial, leading to its approval by the European Medicines Agency (EMA) in patients with relapsed/refractory (R/R) follicular lymphoma (FL). However, real-life data on idelalisib are scarce. We treated 55 double-refractory FL patients with idelalisib in a real-life setting.

Nurses' Physical and Psychological Symptoms During the first COVID-19 Lockdown in Italy: a Nationwide Cross-Sectional Study in Stem Cell Transplantation Setting.

Background And Objective: Northern Italy was one of the first European territories to deal with the Coronavirus Disease 2019 (COVID-19) outbreak. Drastic emergency restrictions were introduced to contain the spread and limit pressure on healthcare facilities. However, nurses were at high risk of developing physical, mental, and working issues due to professional exposure.

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms.

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study.

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19.

[What is the best treatment for chronic-phase CML?].

The chronic myeloid leukemia (CML) therapeutic landscape has dramatically changed with the development of tyrosine kinase inhibitors (TKIs), which allows for a near-normal life expectancy. Five TKIs have been currently approved for CML treatment in Japan, of which four have been indicated as first-line therapy (i.e.

Safety of FLT3 inhibitors in patients with acute myeloid leukemia.

Acute myeloblastic leukemia (AML) is the most frequent type of acute leukemia in adults with an incidence of 4.2 cases per 100,000 inhabitants and poor 5-year survival. Patients with mutations in the FMS-like tyrosine kinase 3 ( gene have poor survival and higher relapse rates compared with wild-type cases.

Iron Toxicity and Chelation Therapy in Hematopoietic Stem Cell Transplant.

Many patients with hematologic malignancies receive RBC transfusion support, which often causes systemic and tissue iron toxicity. Because of their compromised bone marrow function, hematopoietic stem cell transplant (HSCT) recipients are especially vulnerable to excess iron levels. Iron toxicity may compromise transplant engraftment and eventually promote relapse by mediating oxidative and genotoxic stress in hematopoietic stem cells (HSCs) and further impairing the already dysfunctional bone marrow microenvironment in HSCT recipients.

IDH1/IDH2 Inhibition in Acute Myeloid Leukemia.

Recently, the discovery of biological and clinical properties of mutated isoforms 1 and 2 mutations of isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients with acute myeloid leukemia (AML), lead to the development of an individualized treatment strategy. Promoting differentiation and maturation of the malignant clone targeting IDH is an emerging strategy to promote clinical responses in AML. Phase I/II trials have shown evidence of safety, tolerability, and encouraging evidence of efficacy of two small molecule inhibitors targeting IDH2 and IDH1 gene mutations, respectively enasidenib and ivosidenib.

Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome.

Background: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities.

Methods: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival.

Results: A total of 219 patients (31.

Venetoclax-Based Combinations in Acute Myeloid Leukemia: Current Evidence and Future Directions.

The past decade has witnessed major advances in our understanding of molecular biology, which led to breakthrough novel therapies, importantly including the B-cell lymphoma-2 (BCL-2) inhibitor venetoclax. Notably, venetoclax-based combinations have improved outcomes, including both remission rates and overall survival, of older patients with acute myeloid leukemia (AML) deemed "unfit" for intensive chemotherapy due to age or comorbidities. This has translated into a rapid and widespread use of venetoclax-based combinations in both academic and community-based settings.