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REVIEW
Alireza Mohebbi, Fahimeh Shahriyary, Vida Farrokhi, Bita Bandar, Najmaldin Saki
BACKGROUND: Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML...
April 17, 2024: Leukemia Research
#42
JOURNAL ARTICLE
Mingshan Sun, Shijie Li, Zhenyi Liu, Sai Ma, Xiaohan Liu, Qing Meng, Yueyue Zheng, Chunyan Chen
PURPOSE: To assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP). RESULTS: Among 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79...
April 26, 2024: Leukemia Research
#43
JOURNAL ARTICLE
Jad Othman, Nicola Potter, Adam Ivey, Yanis Tazi, Elli Papaemmanuil, Jelena Jovanovic, Sylvie D Freeman, Amanda Frances Gilkes, Rosemary E Gale, Tanya Rapoz-D'Silva, Manohursingh Runglall, Michelle Kleeman, Pawan Dhami, Ian Thomas, Sean Johnson, Joanna Canham, James Durrell Cavenagh, Panagiotis Kottaridis, Claire Arnold, Hans Beier Ommen, Ulrik Malthe Overgaard, Mike Dennis, Alan Kenneth Burnett, Charlotte S Wilhelm-Benartzi, Brian Jp Huntly, Nigel H Russell, Richard James Dillon
Although NPM1-mutated acute myeloid leukemia (AML) carries a generally favorable prognosis, many patients still relapse and die. Previous studies identified several molecular and clinical features associated with poor outcome, however only FLT3-ITD mutation and adverse karyotype are currently used for risk stratification due to inconsistent results and uncertainty around how other factors should influence treatment, particularly given the strong prognostic impact of post-induction measurable residual disease (MRD)...
May 1, 2024: Blood
#44
Geena Jung, Emery Buckner-Wolfson, Adit Tal, Ryan Fatemi, Timothy Kim, Genesis Liriano, Andrew Kobets
Introduction Relapsed acute lymphoblastic leukemia (ALL) involving the central nervous system (CNS) is a significant issue that contributes to both morbidity and mortality. Given the poor outcomes in patients with CNS relapse, understanding how ALL involving intracranial relapse presents and is treated is critical. Here, we present a complex case of relapsed recurrent ALL in a pediatric patient. Case Report An 11-year-old patient presented with double relapse of ALL in the form of an extensive skull base lesion and again with leptomeningeal disease...
April 2024: Journal of Neurological Surgery Reports
#45
Harrison Labban, Farhana Begum, Awais Paracha, Veena John, Mohammed Islam
Severe vitamin B12 deficiency presents a diagnostic challenge due to its diverse clinical manifestations, which can mimic serious hematologic disorders such as thrombotic thrombocytopenic purpura (TTP) or leukemia. The case we present here illustrates the unique characteristics of severe B12 deficiency, highlighting key differentiators from other conditions, including decreased reticulocyte counts and markedly elevated lactate dehydrogenase levels indicative of suppressed erythropoiesis. Advanced cobalamin deficiency affects all cell lines, leading to peripheral pancytopenia...
March 2024: Curēus
#46
JOURNAL ARTICLE
Kanwal M Hameed, Dominique R Bollino, Amol C Shetty, Brandon Carter-Cooper, Rena G Lapidus, Ashkan Emadi
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by disrupted blood cell production and function. Recent investigations have highlighted the potential of targeting glutamine metabolism as a promising therapeutic approach for AML. Asparaginases, enzymes that deplete circulating glutamine and asparagine, are approved for the treatment of acute lymphoblastic leukemia, but are also under investigation in AML, with promising results. We previously reported an elevation in plasma serine levels following treatment with Erwinia -derived asparaginase (also called crisantaspase)...
2024: Frontiers in Oncology
#47
JOURNAL ARTICLE
Patrycja Sosnowska-Sienkiewicz, Sebastian Moryciński, Danuta Januszkiewicz-Lewandowska, Karolina Michalik, Klaudyna Madziar, Agata Kukfisz, Daria Zielińska, Przemysław Mańkowski
INTRODUCTION: Totally Implantable Venous Access Devices (TIVADs) contribute significantly to the treatment progress and comfort of patients requiring long-term therapy. However, the procedure for implanting TIVADs, as well as its very presence, may be associated with complications. AIM: This study evaluates the indications, safety, and complication rates of venous port implantations in pediatric patients. It also explores factors influencing the occurrence of early and late complications post-implantation...
2024: Frontiers in Oncology
#48
JOURNAL ARTICLE
Alan S Futran, Tao Lu, Katherine Amberg-Johnson, Jiayi Xu, Xiaoxiao Yang, Saidi He, Sarah Boyce, Jeffrey A Bell, Robert Pelletier, Takao Suzuki, Xianhai Huang, Heng Qian, Liping Fang, Li Xing, Zhaowu Xu, Stephen E Kurtz, Jeffrey W Tyner, Wayne Tang, Tao Guo, Karen Akinsanya, David Madge, Kristian K Jensen
The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303. FX1-5303 was used as a chemical probe to study the USP7-mediated regulation of p53 signaling in cells. It demonstrates mechanistic differences compared to MDM2 antagonists, a related class of anti-tumor agents that act along the same pathway...
May 17, 2024: IScience
#49
JOURNAL ARTICLE
Longitudinal changes in body mass index, height, and weight in children with acute myeloid leukemia.
Xiaojia Wen, Hongbo He, Ruidong Zhang, Ying Wu, Yuanyuan Zhang, Wei Lin, Jiaole Yu, Jia Fan, Pengli Huang, Jiajia Chen, Wenjing Li, Chunxiu Gong, Huyong Zheng
BACKGROUND: This study reported height prediction and longitudinal growth changes in Chinese pediatric patients with acute myeloid leukemia (AML) during and after treatment and their associations with outcomes. METHODS: Changes in 88 children with AML in percentages according to the growth percentile curve for Chinese boys/girls aged 2-18/0-2 years for body mass index (BMI), height, and weight from the time of diagnosis to 2 years off therapy were evaluated. The outcomes of AML were compared among patients with different BMI levels...
April 30, 2024: BMC Pediatrics
#50
JOURNAL ARTICLE
Enrico Gallo, Carlo Diaferia, Giovanni Smaldone, Elisabetta Rosa, Giovanni Pecoraro, Giancarlo Morelli, Antonella Accardo
Dexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated...
April 30, 2024: Scientific Reports
#51
JOURNAL ARTICLE
Daniela Cesana, Maria Pia Cicalese, Andrea Calabria, Pietro Merli, Roberta Caruso, Monica Volpin, Laura Rudilosso, Maddalena Migliavacca, Federica Barzaghi, Claudia Fossati, Francesco Gazzo, Simone Pizzi, Andrea Ciolfi, Alessandro Bruselles, Francesca Tucci, Giulio Spinozzi, Giulia Pais, Fabrizio Benedicenti, Matteo Barcella, Ivan Merelli, Pierangela Gallina, Stefania Giannelli, Francesca Dionisio, Serena Scala, Miriam Casiraghi, Luisa Strocchio, Luciana Vinti, Lucia Pacillo, Eleonora Draghi, Marcella Cesana, Sara Riccardo, Chiara Colantuono, Emmanuelle Six, Marina Cavazzana, Filippo Carlucci, Manfred Schmidt, Caterina Cancrini, Fabio Ciceri, Luca Vago, Davide Cacchiarelli, Bernhard Gentner, Luigi Naldini, Marco Tartaglia, Eugenio Montini, Franco Locatelli, Alessandro Aiuti
Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment. The patient underwent chemotherapy and haploidentical transplantation and is currently in remission. Blast cells contain a single vector insertion activating the LIM-only protein 2 (LMO2) proto-oncogene, confirmed by physical interaction, and low Adenosine Deaminase (ADA) activity resulting from methylation of viral promoter...
April 30, 2024: Nature Communications
#52
JOURNAL ARTICLE
Sanjay Rathod, Keito Hoshitsuki, Yin Zhu, Manda Ramsey, Christian A Fernandez
BACKGROUND: Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNase-induced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. METHODS: Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation...
2024: Frontiers in Immunology
#53
JOURNAL ARTICLE
Carolyn Brandt, Jacqueline B Vo, Gretchen L Gierach, Iona Cheng, Vanessa N Torres, Wayne R Lawrence, Lauren E McCullough, Lene H S Veiga, Amy Berrington de González, Cody Ramin
Breast cancer survivors have an increased risk of developing second primary cancers, yet risks by race and ethnicity have not been comprehensively described. We evaluated second primary cancer risks among 717,335 women diagnosed with first primary breast cancer (aged 20-84 years and survived ≥1-year) in the SEER registries using standardized incidence ratios (SIRs; observed/expected). SIRs were estimated by race and ethnicity compared with the racial- and ethnic-matched general population, and further stratified by clinical characteristics of the index breast cancer...
April 29, 2024: International Journal of Cancer. Journal International du Cancer
#54
JOURNAL ARTICLE
Carole Scheifer, Bénédicte Lebrun-Vignes, Pascal Lebray, Florence Tubach, Agnès Dechartres
BACKGROUND AND AIMS: A recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection. METHODS: We conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls...
April 27, 2024: Clinics and Research in Hepatology and Gastroenterology
#55
JOURNAL ARTICLE
Hussein Awada, Carmelo Gurnari, Valeria Visconte, Arda Durmaz, Teodora Kuzmanovic, Hassan Awada, Zheng Jin Tu, James R Cook, Brian J Bolwell, Ronald Sobecks, Matt Kalaycio, David Bosler, Jaroslaw P Maciejewski
Therapy-related myeloid neoplasms (tMN) are complications of cytotoxic therapies. Risk of tMN is high in recipients of autologous hematopoietic stem cell transplantation (aHSCT). Acquisition of genomic mutations represents a key pathogenic driver but the origins, timing and dynamics, particularly in the context of preexisting or emergent clonal hematopoiesis (CH), have not been sufficiently clarified. We studied a cohort of 1507 patients undergoing aHSCT and a cohort of 263 patients who developed tMN without aHSCT to determine clinico-molecular features unique to post-aHSCT tMN...
April 29, 2024: Leukemia
#56
JOURNAL ARTICLE
Suellen L R Silva, Ingrid R S B Dias, Ana Carolina B da C Rodrigues, Rafaela G A Costa, Maiara de S Oliveira, Gabriela A da C Barbosa, Milena B P Soares, Rosane B Dias, Ludmila F Valverde, Clarissa A G Rocha, Nainita Roy, Christopher Y Park, Daniel P Bezerra
Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells...
April 29, 2024: Cell Death Discovery
#57
JOURNAL ARTICLE
Hideki Nakasone
Hematopoietic cell transplantation (HCT) is considered a curative treatment for hematological malignancies. However, HCT recipients often face complications such as graft-versus-host disease (GVHD) and disease relapse. Clinical factors like age and HLA disparity are recognized as risks for GVHD. Notably, sex-mismatched HCT, particularly with female donors and male recipients (F→M), is reported to increase the risk of chronic GVHD. This adverse effect of F→M HCT is thought to result from allogeneic immune response against minor histocompatibility antigens encoded on the Y-chromosome of a male recipient (HY-antigens)...
2024: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
#58
JOURNAL ARTICLE
Gentaro Koyama, Takeharu Kawaguchi, Takumi Sato, Chihiro Hamada, Satoru Hara
A 69-year-old woman was referred to our hospital due to hyperleukocytosis. We diagnosed acute myeloid leukemia and started induction therapy with the CAG regimen (aclarubicin, cytarabine and filgrastim). However, the patient was refractory to the initial treatment and developed quadriplegia, and a cerebrospinal fluid (CSF) test showed elevated blasts. We then performed intrathecal chemotherapy, and the number of blasts in CSF gradually decreased. But only two cycles of intrathecal therapy were possible due to severe methotrexate-induced mucositis...
2024: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
#59
JOURNAL ARTICLE
Anna Ruiz-Llobet, Susanna Gassiot, Edurne Sarrate, Josune Zubicaray, Susana Rives, Warda Suleman, Ruben Berrueco
BACKGROUND: Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. The aim of this prospective cohort study was to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children. METHODS: TGT (automated analyzer ST Genesia; ThromboScreen) and pro and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines...
April 29, 2024: Thrombosis and Haemostasis
#60
JOURNAL ARTICLE
Elizabeth F Krakow, Michelle Brault, Corinne Summers, Tanya M Cunningham, Melinda A Biernacki, R Graeme Black, Kyle Blake Woodward, Nicole Vartanian, Sami B Kanaan, Albert C Yeh, Robson G Dossa, Merav Bar, Ryan D Cassaday, Ann Dahlberg, Brian G Till, Andrew E Denker, Cecilia C S Yeung, Ted A Gooley, David G Maloney, Stanley R Riddell, Philip D Greenberg, Aude G Chapuis, Evan W Newell, Scott N Furlan, Marie Bleakley
Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective anti-leukemic effect post-HCT. We conducted a phase I clinical trial employing a novel TCR-T product targeting the minor H antigen HA-1 to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms...
April 29, 2024: Blood
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