Old Therapy, New Questions: Rethinking Phlebotomy in a Pharmacologic Landscape.

Therapeutic phlebotomy remains a key intervention in the management of erythrocytosis and iron overload disorders, particularly polycythemia vera (PV) and hereditary hemochromatosis. Despite its historical origins as an ancient practice, venesection continues to be recommended in international guidelines for the reduction of hematocrit and iron burden, thereby mitigating thrombotic and organ-related complications. However, the evolving landscape of targeted pharmacologic therapies is reshaping the therapeutic paradigm.

Revised "iRR6" model in intermediate-1 risk myelofibrosis patients treated with ruxolitinib.

Background: The response to ruxolitinib after 6 months (RR6) model allows early identification of ruxolitinib-treated myelofibrosis (MF) patients with poorer overall survival (OS); however, it is less applicable to lower-risk patients.

Methods: To further explore this, the authors performed a subanalysis of the "RUX-MF" study (NCT06516406) with an aim to validate the RR6 and to develop a score specific for intermediate-1 DIPSS/MYSEC-PM risk patients.

Results: Among the 776 evaluable patients, 34.

Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study.

: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders.

Real-World Outcomes in -ITD Mutated Acute Myeloid Leukemia: Impact of NPM1 Mutations and Allogeneic Transplantation in a Retrospective Unicentric Cohort.

: Acute myeloid leukemia (AML) with internal tandem duplication (-ITD) mutations carries a poor prognosis. While inhibitors like midostaurin show benefits in combination with chemotherapy, the role of allelic ratio (AR), mutation status, and hematopoietic stem cell transplantation (HSCT) remains uncertain. Real-world data can help refine prognostic classification and treatment strategies.

Length of Washout Period After Remission Does Not Influence Relapse Risk in Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents Combined with Venetoclax.

The combination of venetoclax (VEN) and hypomethylating agents (HMA), such as azacitidine (AZA) or decitabine (DEC), has transformed the treatment landscape for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy. However, optimal management of neutropenia and the impact of post-remission treatment interruptions (washouts) remain unclear. This study aimed to evaluate the safety and efficacy of post-remission washouts and their effect on clinical outcomes.

QRISK3 score is predictive of thrombotic risk in patients with myeloproliferative neoplasms.

Thromboembolic events (TE) represent the commonest cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythaemia (ET). The QRISK3 model is a tool for predicting TE in the general population, with 7.5% recognised as a threshold to identify high-risk patients.

Integration of [F]FDG-PET radiomics with liquid biopsy improves outcome prediction in newly diagnosed diffuse large B-cell lymphoma.

Early identification of relapsing/refractory diffuse large B-cell lymphoma (DLBCL) represents an unmet clinical need. A real-life cohort of newly diagnosed DLBCL (n = 120) treated with R-CHOP was investigated. Using the standardized uptake value (SUV) threshold of 4.

In vivo Effects of Disease-modifying Therapies on Immunological Subsets in Patients with Relapsing-Remitting Multiple Sclerosis.

Background: Disease-modifying therapies (DMTs) are aimed at controlling Multiple Sclerosis disease by modulating or suppressing the immune system. However, there is limited data on changes in immune cell subsets induced by these treatments.

Objective: To assess differences in myeloid, T-, and B-cell subsets in the peripheral blood of relapsing- remitting MS (RR-MS) patients treated with different DMTs.

Recommendations for best management of polycythemia vera in Italy: a Delphi consensus statement.

A two-round Delphi panel study assessed consensus among Italian healthcare professionals on the management of polycythemia vera (PV). Six hematologists with expertise in PV developed an online questionnaire containing 39 statements covering PV diagnosis and prognosis, treatment, management of complications, patient referral between transfusionist and hematologist, and patient education/psychosocial support. An Expert Panel of 18 transfusionists/hematologists rated their level of agreement with each statement on a 5-point Likert scale.

Impact of ELN clinical signs and symptoms on the thrombotic risk in polycythemia vera patients treated with front-line hydroxyurea.

The European LeukemiaNet recently proposed specific Clinical Signs and Symptoms (CSSs) that may trigger cytoreduction in patients with polycythemia vera (PV) at low thrombotic risk (LR). To evaluate the impact of CSSs on the thrombotic risk of patients at LR, high risk by age only (HR-AGE) or by previous thrombosis (HR-THRO), we conducted a multicenter cooperative study (NCT06134102) involving 739 PV patients treated with first-line hydroxyurea. At hydroxyurea start, 443 patients had at least one CSS.

Unmet Needs and Their Impact on Quality of Life and Symptoms in Myelodysplastic Neoplasm Patients and Caregivers.

Background/objectives: The aim of this study was to assess the unmet needs of myelodysplastic neoplasm (MDS) patients and their caregivers, focusing on how these needs impact quality of life (QoL) and daily functioning. MDS predominantly affects older adults. It is often complicated by severe red blood cell transfusion-dependent anemia and may require frequent hospital visits, conferring a substantial burden on patients and caregivers.

Emerging Therapeutic Approaches for Anemia in Myelofibrosis.

Purpose Of Review: In this review, we highlight conventional agents and novel emerging therapeutic strategies to treat anemia in MF.

Recent Findings: Anemia is a common and challenging feature of myelofibrosis (MF). The pathobiology of anemia is multifactorial, including progressive bone marrow fibrosis, decreased erythropoiesis due to high hepcidin levels leading to iron sequestration in the reticuloendothelial system, hypersplenism, erythropoiesis inhibition by myelosuppressive JAK inhibitors (ruxolitinib, fedratinib), and others.

Disease Phenotype Significantly Influences the Outcome After Discontinuation of Ruxolitinib in Chronic Phase Myelofibrosis.

Introduction: In patients with myelofibrosis (MF), overall survival (OS) after ruxolitinib discontinuation is poor, with leukemic transformation, clonal evolution and thrombocytopenia as the main factors worsening prognosis.

Patients And Methods: To assess the impact of disease phenotype on outcome after ruxolitinib discontinuation in chronic phase patients, we performed a sub-analysis of the "RUX-MF" study (NCT06516406), which now includes 1055 MF patients who received ruxolitinib in a real-life context.

Results: After a median follow-up of 3.

Patient and physician perceptions regarding treatment expectations and symptomatology in polycythemia vera: Insights from the Landmark 2.0 global health survey.

Polycythemia vera (PV) is a myeloproliferative neoplasm associated with a high symptom and psychological burden, resulting in decreased quality of life (QoL). Patients with PV have an increased risk of cardiovascular (CV) complications, making regular monitoring crucial. The Landmark 2.

Anemia and blood transfusions in myelofibrosis: economic and organizational impact on Italian patients, caregivers and hospitals.

Introduction: Anemia management in myelofibrosis (MF) remains a major challenge, often resulting in blood transfusions as the condition progresses. The BEAT project aimed to quantify the economic and organizational burden of anemia and transfusions in MF patients in Italy from the patient and hospital perspectives.

Methods: Data were collected from two primary sources: (i) semi-structured interviews with 13 hematologists and 1 transfusionist from 13 Italian MF reference centers; (ii) an online questionnaire completed by 191 patients distributed by AIPAMM (Italian Association of Patients with Myeloproliferative Diseases).

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI).

Background: Myelofibrosis (MF) significantly impacts patients' overall survival (OS) and quality of life (QOL). This prospective study analyzed ruxolitinib dosing patterns and associated clinical outcomes in patients with MF over 12 months.

Methods: ROMEI, a multicenter, observational, ongoing study, enrolled 508 adult patients with MF treated with ruxolitinib.

Immune Response and Breakthrough Infection Risk After SARS-CoV-2 Vaccines in Patients with Hemoglobinopathy: A Single Center Experience.

Background: Immune system impairment is frequently reported in patients affected by hemoglobinopathies due to various mechanisms, including iron accumulation, antigenic stimulation due to numerous transfusions, chronic hemolysis, and a general hyperinflammatory state. For these reasons, the antigenic immune response after a vaccine risks being ineffective.

Methods: We evaluated the anti-spike IgG production after two doses of vaccine for SARS-CoV-2 in patients affected by hemoglobinopathies.

Psychometric properties and meaningful change thresholds for the QOL-E instrument in patients with myelodysplastic neoplasms.

Background: Myelodysplastic neoplasms (MDS) are characterized by ineffective hematopoiesis, peripheral blood cytopenias, and an increased risk of progression to acute myeloid leukemia. One of the main treatment goals is improving quality of life (QoL), particularly for patients with lower-risk MDS (LR-MDS) who may live longer with compromised QoL. The QOL-E is a patient-reported outcome (PRO) measure specifically developed to address the lack of a health-related QoL questionnaire for patients with MDS.

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.

Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis.

Background: Clonal myeloproliferation and fibrotic transformation of the bone marrow (BM) are the pathogenetic events most commonly occurring in myelofibrosis (MF). There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule.

Methods: To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients' sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets.

Emergencies in Hematology: Why, When and How I Treat?

Hematological emergencies are critical medical conditions that require immediate attention due to their rapid progression and life-threatening nature. As various examples, hypercalcemia, often associated with cancers such as multiple myeloma, can lead to severe neurological and cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis and multiorgan failure.

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS).