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.

Treatment-Free Remission in Chronic Phase Chronic Myeloid Leukemia After Nilotinib De-Escalation: 96-Week Update of the DANTE Study.

Treatment-free remission (TFR) in chronic myeloid leukemia (CML) can be considered for patients in sustained deep molecular response (DMR) who can discontinue tyrosine kinase inhibitors (TKIs) while maintaining responses. Studies suggest that TKI de-escalation before TFR is feasible. This phase II study evaluated nilotinib de-escalation outcomes in adults with CML in chronic phase (CP) treated with first-line nilotinib for ≥ 3 years and in sustained DMR for ≥ 1 year.

Exploring thromboembolic risk factors in polycythemia vera: from current evidence to PROSPERO study design.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm with a substantial risk of thromboembolic events (TEs), which contribute to morbidity and mortality. Traditional thrombotic risk stratification primarily considers age and thrombosis history, yet these parameters alone do not capture the complexity of thrombotic risk. Growing evidence highlights the role of additional factors influencing the risk of TEs, underscoring the need for a more comprehensive approach to patient stratification.

Management of chronic myeloid leukemia in 2025.

Chronic myeloid leukemia (CML) has an annual incidence of approximately two cases per 100,000. The reduction in annual mortality from 10%-20% to 1% with BCR::ABL1 tyrosine kinase inhibitors (TKIs) has resulted in an increased prevalence in the United States of an estimated 150,000 cases in 2025. This translates into a worldwide estimated prevalence of approximately 5 million cases, and hence the need to make TKIs available and affordable to all patients.

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.

Treatment Free Remission (TFR) in Chronic Phase-Chronic Myeloid Leukemia (CP-CML): Analysis of Predictive Factors and Novel Baseline Scoring System to Predict Molecular Relapse.

Background: Treatment free remission (TFR) is a key treatment goal in chronic-phase chronic myeloid leukemia (CP-CML) patients with sustained deep molecular response (DMR). While clinical trials report that approximately 40%-50% of such patients can discontinue tyrosine kinase inhibitors (TKIs) without presenting a molecular relapse (MRec), real-world data remain limited. Optimizing patient selection before TKI discontinuation is crucial for CML management and resource allocation.

Chronic myeloid leukemia outcomes according to baseline risk and first-line treatment in real-world settings: Data from the Italian Network/CML Campus.

Background: Improved outcome has been reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) in sponsored trials.

Methods: This is a multicenter prospective cohort study of consecutive patients with newly diagnosed chronic phase CML from 19 regions in Italy. Baseline treatments and prognostic factors on time to first optimal molecular response (≥ molecular response 3, MR3), time to disease progression, time to death from CML, and overall survival (OS) were analyzed using multivariable Fine and Gray models.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion: report of two cases with different clinical presentation.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (M/LN-eo-TK) such as PDGFRA, PDGFRB, FGFR1, JAK2, FLT3 rearrangement and ETV6::ABL1 fusion include rare and heterogeneous clinical-pathological entities with some similarities, not always associated with peripheral eosinophilia. Accurate diagnosis and demonstration of the specific genetic substrate have important implications since target therapy is possibly available. Herein we report two cases showing different bone marrow features and clinical presentation.

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.

Real-World Efficacy Profile of Compassionate Use of Asciminib in an Italian, Multi-Resistant Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Patient Population.

Chronic myeloid leukemia (CML) patients who have experienced failure and/or intolerance to multiple lines of treatment have limited therapeutic possibilities. Asciminib is a first-in-class tyrosine kinase inhibitor (TKI) that inhibits the ABL Myristoyl Pocket (STAMP or Specifically Targeting the ABL Myristoyl Pocket) within the BCR::ABL1 oncoprotein. This retrospective Italian analysis reports the efficacy and safety outcomes of asciminib in treating 77 CML patients in chronic phase (CML-CP) within a compassionate use setting.

Therapeutic Vaccinations with p210 Peptides in Imatinib-Treated Chronic Myeloid Leukemia Patients: 10 Years Follow-Up of GIMEMA CML0206 and SI0207 Studies.

We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. : From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 and SI0207, enrolling overall 109 CML patients (68 b3a2 and 41 b2a2) with persistence of molecular disease during imatinib treatment, were carried out. Peptide vaccination schedule included the following: "immunization phase" (six vaccinations every 2 weeks); "reinforcement" phase (three monthly boosts) and "maintenance" phase (two boosts at 3-month intervals).

CD99 expression in acute myeloid leukemia with FLT3 internal tandem duplications (FLT3-ITD-AML): a flow-cytometric marker for an accurate diagnostic workup.

Internal tandem duplications of FLT3 (FLT3-ITD) in acute myeloid leukemia (AML) are associated with poor outcomes. CD99 is frequently overexpressed in AML and emerged as potential diagnostic marker. Ninety consecutive newly diagnosed AML patients were retrospectively analyzed.

SOHO State of the Art Updates and Next Questions. Atypical Chronic Myeloid Leukemia: Pathogenesis, Diagnostic Challenges, and Therapeutic Strategies.

Atypical chronic myeloid leukemia (aCML) is a rare and challenging clonal hematopoietic disorder within the myelodysplastic/myeloproliferative neoplasm (MDS/MPN) spectrum. Over the past two decades, substantial progress has been made in understanding the genetic mechanisms driving aCML, revealing a complex and heterogeneous mutational landscape. Key ancestral mutations, such as ASXL1 and ETNK1, have been identified, providing a foundation for the pathogenesis and for the possible emergence of secondary abnormalities, particularly in epigenetic regulation (eg, SETBP1), and in splicing process (eg, SRSF2).

Navigating acute myeloid leukemia towards better outcomes: Treatment pathways and challenges for patients ineligible for intensive chemotherapy.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that affects primarily older individuals. Patients ineligible to receive intensive standard chemotherapy followed by consolidation with/without hematopoietic stem cell transplant have a suboptimal prognosis. In recent years, significant advances have been made in the AML field leading to the development of new anti-leukemic approaches, including lower-intensity therapies specifically developed for patients who are ineligible for intensive chemotherapy.

A network-based approach to overcome BCR::ABL1-independent resistance in chronic myeloid leukemia.

Background: About 40% of relapsed or non-responder tumors exhibit therapeutic resistance in the absence of a clear genetic cause, suggesting a pivotal role of intracellular communication. A deeper understanding of signaling pathways rewiring occurring in resistant cells is crucial to propose alternative effective strategies for cancer patients.

Methods: To achieve this goal, we developed a novel multi-step strategy, which integrates high sensitive mass spectrometry-based phosphoproteomics with network-based analysis.

Asciminib in combination with imatinib, nilotinib, or dasatinib in patients with chronic myeloid leukemia in chronic or accelerated phase: phase 1 study final results.

Data from in vitro and animal studies suggest that asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), synergizes with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) to prevent emergence of and overcome resistance. Combination therapy may provide new treatment options for patients with chronic myeloid leukemia (CML) with suboptimal responses to ATP-competitive TKI monotherapy. Preliminary analysis of asciminib combined with nilotinib, imatinib, or dasatinib in a phase 1 dose-escalation study suggested promising efficacy and safety for patients with CML in chronic phase or accelerated phase treated with prior ATP-competitive TKIs; herein, we present final results from the 3 combination therapy arms.

Asciminib monotherapy in patients with chronic myeloid leukemia in chronic phase without BCR::ABL1 treated with at least 2 prior TKIs: Phase 1 final results.

Asciminib is the first approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP). The present final analysis of the phase 1, open-label, nonrandomized trial (NCT02081378) assessed the long-term safety, tolerability, and antileukemic activity of asciminib in 115 patients with chronic myeloid leukemia in chronic phase without the BCR::ABL1 mutation who received asciminib 10-200 mg twice daily (BID) or 80-200 mg once daily (cutoff: March 14, 2023). Median exposure duration was 5.

SOHO State of the Art Updates and Next Questions | Atypical Chronic Myeloid Leukemia: Pathogenesis, Diagnostic Challenges and Therapeutic Strategies.

Atypical chronic myeloid leukemia (aCML) is a rare and challenging clonal hematopoietic disorder within the myelodysplastic/myeloproliferative neoplasm (MDS/MPN) spectrum. Over the past two decades, substantial progress has been made in understanding the genetic mechanisms driving aCML, revealing a complex and heterogeneous mutational landscape. Key ancestral mutations, such as ASXL1 and ETNK1, have been identified, providing a foundation for the pathogenesis and for the possible emergence of secondary abnormalities, particularly in epigenetic regulation (eg, SETBP1), and in splicing process (eg, SRSF2).

Extracellular vesicles as source of biomarkers in hematological malignancies: looking towards clinical applications.

Introduction: Extracellular vesicles are membranous particles released by cells in physiological and pathological conditions. Their cargo is heterogeneous since it includes different biomolecules such as nucleic acids and proteins. Oncogenic alterations affect the composition of extracellular vesicles and model their content during cancer evolution.

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.