Hematology Reports最新文献

{"title":"A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia","authors":"A. Candoni, Gabriele Coppola","doi":"10.3390/hematolrep16020024","DOIUrl":"https://doi.org/10.3390/hematolrep16020024","url":null,"abstract":"Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents is based on the disruption of the menin–KMT2A complex (consisting of chromatin remodeling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or with mutated NPM1. To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140687976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience","authors":"Bianca Serio, Gabriella Storti, M. D’addona, Lidia Edwige Santoro, Camilla Frieri, D. De Novellis, L. Marano, Giovanna De Santis, R. Guariglia, Ilenia Manfra, E. Urciuoli, S. Luponio, S. Marotta, Denise Morini, Michela Rizzo, Fausto Palmieri, Nicola Cantore, V. Giudice, A. Risitano, Carmine Selleri","doi":"10.3390/hematolrep16020023","DOIUrl":"https://doi.org/10.3390/hematolrep16020023","url":null,"abstract":"Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140692990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring Humoral Response Following BNT162b2 mRNA Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplantation Patients: A Single-Center Prospective Study along with a Brief Review of Current Literature","authors":"J. Asimakopoulos, E. Lalou, George Seferlis, Maria Malliarou, E. Konstantinou, I. Drandakis, Ioannis Vasilopoulos, Angeliki N Georgopoulou, A. Kopsaftopoulou, Alexandros Machairas, A. Piperidou, Anestis Karapaschalidis, Maria-Ekaterini Lefaki, D. Galopoulos, M. Arapaki, Panagiota Petsa, Ekaterini Benekou, M. Siakantaris, Athanasios G. Papavassiliou, P. Tsaftaridis, P. Panayiotidis, Theodoros P Vassilakopoulos, A. Papapanagiotou, M. Angelopoulou","doi":"10.3390/hematolrep16020022","DOIUrl":"https://doi.org/10.3390/hematolrep16020022","url":null,"abstract":"Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients—mostly autologous from a single Unit—along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated—p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140696831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiology, Clinical Manifestations and Diagnosis of Immune Thrombocytopenia: Contextualization from a Historical Perspective","authors":"Daniel Martínez-Carballeira, Ángel Bernardo, Alberto Caro, Inmaculada Soto, Laura Gutiérrez","doi":"10.3390/hematolrep16020021","DOIUrl":"https://doi.org/10.3390/hematolrep16020021","url":null,"abstract":"Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in the platelet count and an increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the immune system and causing both peripheral destruction of platelets and impaired central megakaryopoiesis and platelet production in the bone marrow. Here, we intend to contextualize the current knowledge on the pathophysiology, terminology, epidemiology, clinical manifestations, diagnosis, and prognosis of ITP from a historical perspective and the first references to the never-stopping garnering of knowledge about this entity. We highlight the necessity to better understand ITP in order to be able to provide ITP patients with personalized treatment options, improving disease prognosis and reducing the incidence or frequency of refractoriness.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ophthalmic Manifestations in Patients with Blood Malignancies","authors":"Costanza Rossi, Alessandro Buizza, Giuseppe Alessio, Massimiliano Borselli, A. Taloni, A. Carnevali, Giovanna Carnovale Scalzo, A. Lucisano, Vincenzo Scorcia, Giuseppe Giannaccare","doi":"10.3390/hematolrep16020020","DOIUrl":"https://doi.org/10.3390/hematolrep16020020","url":null,"abstract":"Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140370728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partial Splenic Embolization in a Patient with Hemophilia A and Severe Thrombocytopenia: A Case Report","authors":"Tomofumi Nakamura, Mitsuhiro Uchiba, Hirotomo Nakata, Takao Mizumoto, Toru Beppu, Shuzo Matsushita","doi":"10.3390/hematolrep16020019","DOIUrl":"https://doi.org/10.3390/hematolrep16020019","url":null,"abstract":"We report a patient with hemophilia A who underwent partial splenic embolization (PSE) for severe thrombocytopenia secondary to portal hypertension-induced splenomegaly, resulting in a stable long-term quality of life. The patient was diagnosed with hemophilia A and unfortunately contracted human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) from blood products. He subsequently developed progressive splenomegaly due to portal hypertension from chronic HCV, resulting in severe thrombocytopenia. PSE was performed because he had occasional subcutaneous bleeding and needed to start interferon (IFN) and ribavirin (RBV) treatment for curing his HCV infection at that time. His platelet counts increased, and no serious adverse events were observed. Currently, he continues to receive outpatient treatment, regular factor VIII (FVIII) replacement therapy for hemophilia A, and antiretroviral therapy for HIV infection. Vascular embolization has been reported to be an effective and minimally invasive treatment for bleeding in hemophilia patients. PSE also provided him with a stable quality of life without the side effects of serious infections and thrombocytopenia relapses. We conclude that PSE is a promising therapeutic option for patients with hemophilia A.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140379088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indolent T Cell Lymphoproliferation of the Gastrointestinal Tract: An Evolving Disease Entity.","authors":"Luke Wang, Elaine Koh, Beena Kumar, Michael S Y Low","doi":"10.3390/hematolrep16020018","DOIUrl":"10.3390/hematolrep16020018","url":null,"abstract":"<p><p><b>Background:</b> Indolent T cell lymphoproliferation of the gastrointestinal tract is a novel entity recently added to the 2016 WHO classification of lymphoid neoplasms. Classically, these patients demonstrate an immunophenotype consistent with T cell proliferation and can be either CD4-positive or CD8-positive but with a low Ki67 index, highlighting the indolent nature of this disease compared to its more aggressive T cell lymphoma counterparts such as enteropathy-associated T cell lymphoma and monomorphic epitheliotropic intestinal T cell lymphoma. <b>Methods:</b> Here, we describe one rare case of such a neoplasm under our care, initially presenting with non-specific signs and symptoms and requiring extensive investigations to diagnose. Available cases in the literature reflect a wide variety of ages and ethnicities affected, and any part of the gastrointestinal sites can be affected, which makes diagnosis difficult and prolonged; however, progression beyond lymph nodes is rare, and prognosis is otherwise favourable, particularly if CD8-positive. The optimal management of these patients remains yet to be defined, given the paucity of available cases currently. The current evidence suggests the utility of steroids, cyclosporine, radiotherapy, and a potential role for JAK inhibitors. <b>Conclusions:</b> Our case showed an excellent response to the initial course of steroids, with a subsequent successful transition to cyclosporine, keeping symptoms at bay with ongoing stable disease.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating Lymphomas through BCR Signaling and Double-Hit Insights: Overview","authors":"Antonella Argentiero, Alessandro Andriano, Donatello Marziliano, V. Desantis","doi":"10.3390/hematolrep16010017","DOIUrl":"https://doi.org/10.3390/hematolrep16010017","url":null,"abstract":"Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating from B, T, or NK lymphocytes. They represent approximately 4–5% of new cancer cases and are classified according to the revised WHO system based on cell lineage, morphology, immunophenotype, and genetics. Diagnosis requires adequate biopsy material, though integrated approaches are used for leukemic presentations. Molecular profiling is improving classification and identifying prognostic markers. Indolent NHLs, such as follicular lymphoma and marginal zone lymphoma, typically pursue a non-aggressive clinical course with long survival. Aggressive diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Recent studies have elucidated pathogenic mechanisms like MYC translocations and BCR pathway mutations. “Double hit” lymphomas with MYC and BCL2/BCL6 alterations confer a poor prognosis. Treatment approaches are evolving, with chemoimmunotherapy remaining standard for many indolent cases while intensified regimens and targeted agents show promise for refractory or high-risk aggressive disease. Continued elucidation of the genetic and microenvironmental underpinnings of lymphomagenesis is critical for developing personalized therapeutic strategies.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140221914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug–Drug Interactions of FXI Inhibitors: Clinical Relevance","authors":"Nicola Ferri, Elisa Colombo, Alberto Corsini","doi":"10.3390/hematolrep16010016","DOIUrl":"https://doi.org/10.3390/hematolrep16010016","url":null,"abstract":"Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug–drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140222708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia","authors":"María Nieves Sáez Perdomo, R. Stuckey, Elena González-Pérez, Santiago Sánchez-Sosa, Paula Estupiñan-Cabrera, Sunil Lakhwani Lakhwani, J. D. González San Miguel, Nuria Hernanz Soler, Marina Gordillo, Gloria González Brito, María Tapia-Torres, Ana Ruano, Adrián Segura-Díaz, H. Luzardo, C. Bilbao-Sieyro, M. Gómez-Casares","doi":"10.3390/hematolrep16010015","DOIUrl":"https://doi.org/10.3390/hematolrep16010015","url":null,"abstract":"Background: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs. Methods: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML. Result: With a mean follow up of 6 years, 19/210 (9.1%) patients developed VAEs, all of whom presented at least one cardiovascular risk factor at diagnosis. The mean time to VAE presentation was 54 months from the start of TKI treatment. We found a statistically significant difference between the CI for nilotinib-naïve vs. nilotinib-treated patients (p = 0.005), between dasatinib-naïve and dasatinib-treated patients (p = 0.039), and for patients who received three lines of treatment with first-line imatinib vs. first-line imatinib (p < 0.001). From the multivariable logistic regression analyses, the Framingham risk score (FRS) and patients with three lines of TKI with first-line imatinib were the only variables with statistically significant hazard ratios for VAE development. Significant increases in HDL-C and total cholesterol may also be predictive for VAE. Conclusions: In conclusion, it is important to estimate the cardiovascular risk at the diagnosis of CML as it can help determine whether a patient is likely to develop a VAE during TKI treatment.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140249805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}