Mesenchymal stromal cells from myeloproliferative neoplasms support healthy and malignant hematopoiesis in a humanized scaffold model in vivo.

Myeloproliferative Neoplasms (MPN) are malignancies of hematopoietic stem and progenitor cells (HSPCs) that lead to the overproduction of mature blood cells. These disorders include Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), primarily driven by somatic mutations such as . Research indicates that mesenchymal stromal cells (MSCs) support fibrosis in PMF, though their role in ET and PV remains less clear.

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.

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.

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.

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.

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.

Novelties on Multiple Myeloma from the Main 2024 Hematology Conferences.

Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment.

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.

Shaping the Future of Myeloproliferative Neoplasm Therapy: Immune-Based Strategies and Targeted Innovations.

Numerous cutting-edge immunotherapy approaches have been developed for hematological malignancies, such as immune-checkpoint inhibitors for lymphomas, chimeric antigen receptor (CAR)-T-cell treatments for B-cell cancers, and monoclonal antibody therapies for acute myeloid leukemia (AML). However, achieving similar breakthroughs in MPNs has proven challenging. The key obstacles include the absence of universally expressed and MPN-specific surface markers, significant cellular and molecular variability among both individual patients and across different MPN subtypes, and the failure of treatments to stimulate an anti-tumor immune response due to the immune system disruptions caused by the myeloid neoplasm.

Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is a haemato-inflammatory syndrome genetically defined by somatic mutations in the X-linked UBA1 gene, typically Val/Thr/Leu substitutions at the Met41 hotspot. Clinical manifestations are heterogeneous and refractory to most haemato-rheumatological treatments. To date, no guidelines exist for the management of VEXAS, and scarce is the evidence on methodology and clinical significance of longitudinal UBA1 clonal burden evaluation upon therapy.

Multidisciplinary and personalized approach to the management of mycosis fungoides with chlormethine gel: a collection of clinical experiences.

Topical chlormethine (CL) gel formulation was approved by the EMA in 2017 for the treatment of adult patients with mycosis fungoides (MF). To expand the knowledge on the management of MF, this paper provides an overview of clinical practice evidence about the MF diagnostic phase and a collection of clinical experiences to better characterize the use of CL gel in daily practice. Collected cases underline the importance of the concomitant biopsy and clinical evaluation in the diagnostic phase, with the contribution of a multidisciplinary team, and support the use of CL gel as a first-line or adjuvant treatment in selected patients.

The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment.

Epidemiology of cutaneous T-cell lymphomas: state of the art and a focus on the Italian Marche region.

Among primary cutaneous T-cell lymphomas (CTCL), mycosis fungoides (MF) is the most frequent and, along with Sézary syndrome (SS), the best-studied subtype. Most available studies on epidemiology of MF and SS are based on small cohorts or different inclusion criteria. Moreover, although this has become a hot topic, most studies show limitations, such as selection bias and lack of clinical information or follow-up data.