ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis

Cancers, Год журнала: 2023, Номер 16(1), С. 154 - 154

Опубликована: Дек. 28, 2023

Activin receptor type I (ACVR1) is a transmembrane kinase belonging to bone morphogenic protein receptors (BMPs). ACVR1 plays an important role in hematopoiesis and anemia via the BMP6/ACVR1/SMAD pathway, which regulates expression of hepcidin, master regulator iron homeostasis. Elevated hepcidin levels are inversely associated with plasma levels, chronic leads iron-restricted anemia. Anemia one hallmarks myelofibrosis (MF), marrow (BM) malignancy characterized by BM scarring resulting impaired hematopoiesis, splenomegaly, systemic symptoms. red blood cell transfusions negatively impact MF prognosis. Among approved JAK inhibitors (ruxolitinib, fedratinib, momelotinib, pacritinib) for MF, momelotinib pacritinib preferably used cytopenic patients; both agents potent that suppress pathway restore homeostasis/erythropoiesis. In September 2023, was as treatment patients Zilurgisertib (ACVR1 inhibitor) DISC-0974 (anti-hemojuvelin monoclonal antibody) evaluated early phase clinical trials Luspatercept (ACVR2B ligand trap) assessed transfusion-dependent registrational 3 trial. Approved novel development poised improve outcomes anemic patients.

Язык: Английский

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

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(24), С. 7572 - 7572

Опубликована: Дек. 12, 2024

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 severe neurological cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis multiorgan failure. Sickle cell crisis, a complication sickle disease, results from vaso-occlusion, leading pain tissue ischemia. Tumor lysis syndrome, reported cases destruction cancer cells, causes electrolyte imbalances kidney injury. Acute transfusion reactions, fundamental hematological conditions, range mild allergic responses hemolysis shock, requiring prompt management. Disseminated intravascular coagulation, involving excessive coagulation bleeding, is commonly triggered by malignancies, first phases promyelocytic leukemia. Recently, era bispecific antibodies chimeric antigen receptor T cytokine release syndrome manifestation must be recognized promptly treated. Understanding pathophysiology, recognizing clinical manifestations, ensuring adequate diagnostic strategies management approaches for each condition central early intervention improving patient outcomes reducing mortality.

Язык: Английский

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

Vaccines, Год журнала: 2025, Номер 13(2), С. 111 - 111

Опубликована: Янв. 23, 2025

Background: Immune system impairment is frequently reported in patients affected by hemoglobinopathies due to various mechanisms, including iron accumulation, antigenic stimulation numerous transfusions, chronic hemolysis, and a general hyperinflammatory state. For these reasons, the immune response after vaccine risks being ineffective. Methods: We evaluated anti-spike IgG production two doses of for SARS-CoV-2 hemoglobinopathies. Results: All 114 enrolled (100%) developed adequate antibody production, with median value serum 2184.4 BAU/mL (IQR 1127.4–3502.9). The amount was unrelated any other clinical characteristics evaluated, transfusion dependence or non-transfusion dependence, age, gender, disease type, ferritin, blood count, spleen status, therapy hydroxyurea chelators (in all cases p > 0.05). Moreover, 47 (41.2%) breakthrough infection during first 2 years follow-up vaccination, mildly symptomatic course, without requiring hospitalization experiencing significative drop hemoglobin values, allowing slight delay their regimen. Conclusion: Vaccination against COVID-19 safe effective hemoglobinopathies, ensuring protection from severe infection.

Язык: Английский

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Longitudinal immunogenicity cohort study of SARS-CoV-2 mRNA vaccines across individuals with different immunocompromising conditions: heterogeneity in the immune response and crucial role of Omicron-adapted booster doses

EBioMedicine, Год журнала: 2025, Номер 113, С. 105577 - 105577

Опубликована: Фев. 4, 2025

Язык: Английский

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BNT162b2 mRNA vaccination affects the gut microbiome composition of patients with follicular lymphoma and chronic lymphocytic leukemia

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 10, 2025

Abstract Background In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in first wave received BNT162b2 vaccine anti-neoplastic treatment. Methods To capture changes immunome microbiome composition CLL FL upon mRNA-based vaccination, we designed a prospective, longitudinal study profile cellular response after exposure vaccine. Results patients, second third administrations increased titer specific antibodies against SARS-CoV-2. vaccination induced expansion central memory CD8 + CD57dim CD279 T cells reduction neutrophil subset myeloid 1 (CD14 − CD15 CD16 dim CD64 CD33 CD38 PDL1 HLA-DR ); cohorts, CD45RA CD27 NK were expanded full cycle vaccination. After genera Collinsella, Gemmiger, Lachnospiraceae, Blautia, Ruminococcus Lactobacillus whereas Faecalibacterium, Enterobacteriacae, Enterococcus decreased. Multivariate analysis failed identify factors associated with communities among considering age, sex, anti-CD20 therapy disease activity. Only alpha diversity was negatively correlated subsets e 5 at baseline positively 6 PICRUSt2 showed how can also affect host health promoting inflammation. The L-lysine biosynthesis pathway more represented L-valine degradation anaerobic purine nucleobases overrepresented cohort. Conclusions Taken together, our findings reveal effect shaping despite receiving treatment for their underlying active disease, highlight importance comprehensive profiling understand immune function these cohorts patients.

Язык: Английский

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Debulking Therapy with Obinutuzumab Is Helpful and Safe in Chronic Lymphocytic Leukemia with Extreme Hyperleukocytosis: A Case Report

Onco, Год журнала: 2025, Номер 5(1), С. 10 - 10

Опубликована: Март 1, 2025

Chronic lymphocytic leukemia (CLL) represents the most frequent in Western world, with an incidence of 4 [...]

Язык: Английский

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ORCHESTRA Delphi Consensus: diagnostic and therapeutic management of SARS-CoV-2 infection in haematological patients

Clinical Microbiology and Infection, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Polycythemia Vera: Barriers to and Strategies for Optimal Management

Blood and Lymphatic Cancer Targets and Therapy, Год журнала: 2023, Номер Volume 13, С. 77 - 90

Опубликована: Дек. 1, 2023

Abstract: Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality life and severe complications. Despite the increasingly in-depth knowledge this condition, it necessitates multifaceted management approach to mitigate symptoms prevent thrombotic hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection hydroxycarbamide associated with antiplatelet therapy have central role are now accompanied other drugs, such as interferon Janus kinase inhibitors. Ongoing research advancements targeted therapies hold promise for further enhancing choice PV management. Keywords: polycythemia vera, barriers treatment, current approach, future perspectives

Язык: Английский

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Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Март 29, 2023

Patients with multiple myeloma (MM) frequently reported immune impairment an increased risk for infection-related mortality. We aimed to evaluate the response in MM patients vaccinated SARS-CoV-2 during active treatment.We enrolled 158 affected by or smoldering (SMM) and 40 healthy subjects. All subjects received 2 3 doses of BNT162b2 (Pfizer/BioNTech) vaccine, anti-spike IgG values were evaluated after every dose. applied Propensity Score Matching (PSM) as a consequence limited sample size its heterogeneity adjust differences baseline clinical variables between who achieved not vaccine doses.At 30 days from second dose, median antibodies level was 25.2 AU/mL, lower than SMM control group. The same results confirmed third levels MM, compared Following PSM, lack complete vaccination plus boost associated age more 70 years old use high-dose steroids. failed identify association specific treatment types reduced response. prophylaxis tixagevimab/cilgavimab non-responder has proven be effective safe approach reducing serious illness event breakthrough infection, faced mild symptomatic course, providing protection instead long-term humoral responses. only high-risk cytogenetic abnormalities developing infection.Monitoring is fundamental that remain highly vulnerable despite vaccine. can guarantee better severe form disease.

Язык: Английский

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AIPSS‐MF machine learning prognostic score validation in a cohort of myelofibrosis patients treated with ruxolitinib

Cancer Reports, Год журнала: 2023, Номер 6(10)

Опубликована: Авг. 8, 2023

In myelofibrosis (MF), new model scores are continuously proposed to improve the ability better identify patients with worst outcomes. this context, Artificial Intelligence Prognostic Scoring System for Myelofibrosis (AIPSS-MF), and Response Ruxolitinib after 6 months (RR6) during ruxolitinib (RUX) treatment, could play a pivotal role in stratifying these patients.We aimed validate AIPSS-MF MF who started RUX compared standard prognostic at diagnosis RR6 of treatment.At diagnosis, performs than widely used IPSS primary (C-index 0.636 vs. 0.596) MYSEC-PM secondary 0.616 0.593). During we confirmed leading predicting an inadequate response by JAKi therapy (0.682 0.571).The score confirms that it can adequately stratify subgroup already models, laying foundations models developed tailored patient based on artificial intelligence.

Язык: Английский

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