MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.

Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

Allogeneic Hematopoietic Cell Transplantation in Elderly Patients in a Latin American Country: Analysis of 11 Year of Data from the Brazilian Registry SBTMO/CIBMTR.

This study analyzed recent changes in the utilization of allogeneic hematopoietic cell transplantation (HCT) for treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative diseases (MPDs) and the survival of HCT recipients ≥60 years of age in Brazil. This retrospective registry study included patients who received a first allogeneic HCT from any donor between 2012 and 2023. Of the 6657 patients, 444 (7%) were 60 years of age or older who received grafts from human leukocyte antigen (HLA)-matched related (42%) or unrelated (20%) donors or HLA-haploidentical donors (32%).

Mixing oak and eucalyptus sawdusts improves shiitake (Lentinula edodes) yield and nutritional value.

The study aimed to explore suitable substrates comprising locally available hardwood sawdusts for the cultivation of Shiitake (Lentinula edodes) in Lebanon. Sawdusts of oak (OS), maple (MAP), and eucalyptus (EUC) were used alone or in combination, supplemented equally by wheat bran (WB). Results showed that complete mycelia run, fruiting, and harvest dates were the minimum in OS-WB: 800-200 by 72.

The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson's disease.

The impact of LRRK2 variants on the risk of Parkinson's disease in Egyptians remains unknown. We examined 1210 Egyptians (611 PD patients and 599 controls) from 16 governorates across Egypt for 12 LRRK2 pathogenic variants. The p.

Valorization of agro-forest wastes (oak acorns, vineyard pruning, and olive pruning) through the cultivation of shiitake () mushrooms.

Experimental research has been focusing on developing new substrates for growing shiitake mushrooms as alternatives to the standard oak sawdust substrate. The selection of appropriate lignocellulosic materials is based on their availability in the production area and their compatibility with the requirements of the mushroom species being cultivated. In comparison to oak sawdust substrate (OS) as the control, this study evaluated the potential of oak acorns (OA), olive pruning (OLPR), and vineyard pruning (VIP), and various combinations: OA-OLPR:1-1, OA-VIP:1-1, OS-OLPR:1-1, and OS-VIP:1-1, prepared on a dry weight basis.

The Role of Molecular or Cytogenetic Response as a Favorable Prognostic Factor Before Hematopoietic Stem Cell Transplantation for Chronic Myeloid Leukemia.

Tyrosine kinase inhibitors (TKIs) have revolutionized therapy for patients with chronic myeloid leukemia (CML) over the last two decades. However, some patients still do not achieve an adequate response to these drugs, and hematopoietic stem cell transplantation (HSCT) is indicated in this scenario. We present the results of a 20-year follow-up study of 70 patients who underwent transplantation after TKI failure.

Case report: Successful autologous hematopoietic stem cell transplantation in a patient with GAD antibody-spectrum disorder with rapidly progressive dementia.

The prevalence of neurological syndromes associated with antibodies to glutamic acid decarboxylase is increasing. While cognitive impairment is a common feature of this condition, it seldom emerges as the primary symptom. In this study, we discuss a case of refractory dementia associated with the glutamic acid decarboxylase spectrum disorder.

Colonization by multidrug-resistant bacteria in hematological patients undergoing hematopoietic stem cell transplantation and clinical outcomes: A single-center retrospective cohort study.

Background: Bloodstream infections are a leading cause of death in patients who undergo hematopoietic stem cell transplantation (HSCT) and are more severe when caused by multidrug-resistant (MDR) bacteria. This study proposed to investigate if colonization by MDR bacteria negatively affects the clinical outcomes in hematological patients after HSCT, as well as to evaluate possible risk factors for death due to bacteremia by the same colonizing agent.

Methods: A single-center retrospective cohort study was conducted with 405 hematological patients submitted to a single HSCT procedure between 2015 and 2021.

A Phase 3, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate Safety, Tolerability, and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Allogeneic Hematopoietic Cell Transplant Recipients (PNEU-STEM).

Background: Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE; Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Donor-Specific HLA Antibodies Are Associated with Graft Failure and Delayed Hematologic Recovery after Unrelated Donor Hematopoietic Cell Transplantation.

Graft failure (GF) is one of the major concerns after allogeneic hematopoietic cell transplantation (allo-HCT) and remains a significant cause of morbidity and mortality. Although previous reports have associated the presence of donor-specific HLA antibodies (DSAs) with an increased risk of GF after unrelated donor allo-HCT, recent studies have failed to confirm this association. We sought to validate the presence of DSAs as a risk factor for GF and hematologic recovery in the unrelated donor allo-HCT setting.

Untreated Donor-Specific HLA Antibodies Are Associated With Graft Failure and Poor Survival After Haploidentical Transplantation With Post-Transplantation Cyclophosphamide in Pediatric Patients With Nonmalignant Disorders.

Donor-specific HLA antibodies (DSAs) have been recognized as a major risk factor for graft failure (GF) in adult patients with malignancies undergoing haploidentical transplantation with post-transplantation cyclophosphamide (haplo-PTCy). However, the impact of DSAs after pediatric haplo-PTCy for nonmalignant disorders (NMDs) has been poorly reported. We sought to investigate whether preexisting DSAs adversely affect pediatric haplo-PTCy outcomes.

Transplantation for Fanconi anaemia: lessons learned from Brazil.

Fanconi anaemia is a challenging disease to manage, and haematopoietic stem-cell transplantation (HSCT) is the treatment of choice for the haematological complications related to this disease. Over these past two decades, we have observed a substantial improvement in survival outcomes after matched related and unrelated donor HSCT, even for patients living in low-income and middle-income countries. Long-term overall survival is still suboptimal because of the risk of malignancies and other disease-related complications.

Pharmacokinetic/Pharmacodynamic Evaluation of Ivosidenib or Enasidenib Combined With Intensive Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed IDH1/2-Mutant Acute Myeloid Leukemia.

Mutant isocitrate dehydrogenase 1/2 (mIDH1/2) proteins catalyze production of the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib and enasidenib are oral inhibitors of mIDH1 and mIDH2, respectively. An open-label phase 1 study is evaluating the safety and efficacy of ivosidenib or enasidenib combined with intensive induction and consolidation chemotherapy in adult patients with newly diagnosed mIDH1/2 acute myeloid leukemia (AML; NCT02632708).

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. III: anti-CD19 CAR-T cell therapy for patients with non-Hodgkin lymphoma.

The treatment and evolution of B-cell non-Hodgkin lymphoma (B-NHL) has undergone important changes in the last years with the emergence of targeted therapies, such as monoclonal antibodies, small molecules, antibody-drug conjugates, and bispecific antibodies. Nevertheless, a significant portion of patients remains refractory or relapsed (R/R) to the new therapeutic modalities, representing thus an unmet medical need. The use of CAR-T cells for the treatment of B-NHL patients has shown to be a promising therapy with impressive results in patients with R/R disease.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. II: CAR-T cell therapy for patients with CD19+ acute lymphoblastic leukemia.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapeutic modality for acute lymphoblastic leukemia (ALL) with robust outcomes in patients with refractory or relapsed disease. At the same time, CAR-T cell therapy is associated with unique and potentially fatal toxicities, such as cytokine release syndrome (CRS) and neurological toxicities (ICANS). This manuscript aims to provide a consensus of specialists in the fields of Hematology Oncology and Cellular Therapy to make recommendations on the current scenario of the use of CAR-T cells in patients with ALL.

Structural and chemical heterogeneity of Proterozoic organic microfossils of the ca. 1 Ga old Angmaat Formation, Baffin Island, Canada.

Organic microfossils in Meso- and Neoproterozoic rocks are of key importance to track the emergence and evolution of eukaryotic life. An increasing number of studies combine Raman spectroscopy with synchrotron-based methods to characterize these microfossils. A recurring observation is that Raman spectra of organic microfossils show negligible variation on a sample scale and that variation between different samples can be explained by differences in thermal maturation or in the biologic origin of organic precursor material.

Petrographic carbon in ancient sediments constrains Proterozoic Era atmospheric oxygen levels.

Oxygen concentration defines the chemical structure of Earth's ecosystems while it also fuels the metabolism of aerobic organisms. As different aerobes have different oxygen requirements, the evolution of oxygen levels through time has likely impacted both environmental chemistry and the history of life. Understanding the relationship between atmospheric oxygen levels, the chemical environment, and life, however, is hampered by uncertainties in the history of oxygen levels.

The impact of donor-specific anti-human leukocyte antigen antibodies in salvage haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide in patients with nonmalignant disorders.

The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a major risk factor for graft failure (GF) after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (haplo-PTCy). However, the role of DSAs in salvage haplo-PTCy for rescuing patients with nonmalignant disorders (NMDs) has not yet been reported. The present study retrospectively analyzed 22 patients with NMDs who underwent salvage haplo-PTCy from January 2008 to December 2017.

Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study.

Ivosidenib (AG-120) and enasidenib (AG-221) are targeted oral inhibitors of the mutant isocitrate dehydrogenase (mIDH) 1 and 2 enzymes, respectively. Given their effectiveness as single agents in mIDH1/2 relapsed or refractory acute myeloid leukemia (AML), this phase 1 study evaluated the safety and efficacy of ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed mIDH1/2 AML. Ivosidenib 500 mg once daily and enasidenib 100 mg once daily were well tolerated in this setting, with safety profiles generally consistent with those of induction and consolidation chemotherapy alone.

Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019.

A Case Series of Post-Transplantation Cyclophosphamide in Unrelated Donor Hematopoietic Cell Transplantation for Aplastic Anemia.

Patients with severe aplastic anemia (SAA) who fail immunosuppressive therapy have a dismal prognosis. Hematopoietic stem cell transplantation (HSCT) from an unrelated donor (URD) is one of the most effective treatment options. Two institutions have independently adopted a post-transplantation cyclophosphamide (PTCy) approach for patients with SAA undergoing HSCT from a URD.

In situ S-isotope compositions of sulfate and sulfide from the 3.2 Ga Moodies Group, South Africa: A record of oxidative sulfur cycling.

Sulfate minerals are rare in the Archean rock record and largely restricted to the occurrence of barite (BaSO ). The origin of this barite remains controversially debated. The mass-independent fractionation of sulfur isotopes in these and other Archean sedimentary rocks suggests that photolysis of volcanic aerosols in an oxygen-poor atmosphere played an important role in their formation.

Identifying microbial life in rocks: Insights from population morphometry.

The identification of cellular life in the rock record is problematic, since microbial life forms, and particularly bacteria, lack sufficient morphologic complexity to be effectively distinguished from certain abiogenic features in rocks. Examples include organic pore-fillings, hydrocarbon-containing fluid inclusions, organic coatings on exfoliated crystals and biomimetic mineral aggregates (biomorphs). This has led to the interpretation and re-interpretation of individual microstructures in the rock record.

Effect of itraconazole, food, and ethnic origin on the pharmacokinetics of ivosidenib in healthy subjects.

Purpose: To assess the effect of ethnicity, food, and itraconazole (strong CYP3A4 inhibitor) on the pharmacokinetics of ivosidenib after single oral doses in healthy subjects.

Methods: Three phase 1 open-label studies were performed. Study 1: Japanese and Caucasian subjects received single doses of 250, 500, or 1000 mg ivosidenib (NCT03071770).