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Toxicology and carcinogenesis studies of N,N-dimethyl-p-toluidine (CAS No. 99-97-8) in F344/N rats and B6C3F1/N mice (gavage studies).

N,N-dimethyl-p-toluidine was nominated for toxicology and carcinogenesis studies by the National Cancer Institute based on the potential for human exposure through its use in dental materials and bone cements and the lack of toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1/N mice were administered N,N-dimethyl-p-toluidine (greater than 99% pure) in corn oil by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli, mouse peripheral blood, and mouse and rat liver. 3-MONTH STUDY IN RATS: Groups of 10 male

Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico.

BackgroundThe impact of social determinants of health in allogeneic transplant recipients in low- and middle-income countries is poorly described. This observational study analyzes the impact of place of residence, referring institution, and transplant cost coverage (out-of-pocket vs government-funded vs private insurance) on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) in two of Mexico's largest public and private institutions.AimTo evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients i

Indian Society of Hematology and Blood Transfusion (ISHBT) Consensus Document on Hematological Practice During COVID-19 Pandemic.

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COV

Economic Burden of Patients Treated for Higher-Risk Myelodysplastic Syndromes (HR-MDS) in Routine Clinical Care in the United States.

Background and objectiveSignificant clinical burden is associated with higher-risk myelodysplastic syndromes (HR-MDS); however, the economic burden has not been fully examined. We examined cost of care and healthcare utilization (HCU) in HR-MDS patients engaged in routine care in the United States (US).MethodsAdult US patients diagnosed with HR-MDS from 1/1/2008 to 10/31/2015 were identified from the Optum database. Patients were followed until death, progression to acute myeloid leukemia (AML), end of enrollment, or end of study (12/31/2015). Myelodysplastic syndrome (MDS)-related costs/HCU (

A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation.

Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP), rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence

Evolving Paradigms in Chronic Graft-Versus-Host Disease: From Global Immunosuppression to Precision Targeted and Cell-Based Therapies.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment for a range of medical conditions. However, the procedure carries with it a significant risk of chronic graft-versus-host disease (cGVHD), which can have a considerable impact on patients’ quality of life and clinical outcomes. In recent years, there has been a marked shift in treatment strategies for this condition, with greater emphasis being placed on novel targeted therapies and cell therapies that target specific pathways. This shift in approach signifies a more profound comprehension of the pa

Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.

Malignant tumors represent a major threat to human life and health, posing persistent challenges in medical research. While chimeric antigen receptor T (CAR-T) cell therapy has demonstrated breakthrough efficacy in hematological malignancies such as leukemia and lymphoma, its application in solid tumors, including hepatocellular carcinoma, lung cancer, and pancreatic cancer, remains constrained by multiple bottlenecks. These limitations encompass the immunosuppressive tumor microenvironment, insufficient in vivo persistence of CAR-T cells, long-term treatment-induced exhaustion, and off-target

Exosomes-loaded with traditional Chinese medicine constituents: a novel therapeutic avenue for aplastic anemia.

Aplastic anemia (AA) is a life-threatening blood disorder characterized by bone marrow failure and pancytopenia. Treatments such as immunosuppressive therapy (IST) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) have limitations, including poor long-term remission and donor shortages. Exosomes, nanosized extracellular vesicles, are promising drug delivery systems (DDS) due to their biocompatibility, targeted delivery, and capacity to penetrate biological barriers. Traditional Chinese medicine (TCM) regulates hematopoiesis and immunity but faces challenges with delivery. This

Polymorphisms in CXCR3 ligands predict early CXCL9 recovery and severe chronic GVHD.

Chronic graft-versus-host disease (cGVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT). The individual risk of severe cGVHD remains difficult to predict and may involve CXCR3 ligands. This study investigated the role of single-nucleotide polymorphisms (SNPs) of CXCL4, CXCL9, CXCL10, and CXCL11, and their day +28 serum levels, in cGVHD pathogenesis. Eighteen CXCR3 and CXCL4, CXCL9-11 SNPs as well as peri-transplant CXCL9-11 serum levels were analyzed in 688 patients without (training cohort; n = 287) or with statin-based endothelial protection

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients.

Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, h

Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow-Review of Published Literature.

Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients.

Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medic

Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced cell killing.

BackgroundPulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension.Methods and resultsAfter developing pulmonary vascular remodeling in chronic hypoxia or chronic hypoxia/SU-5416 models, rats

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… Doxorubicin‐induced DNA degradation in murine thymocytes. Mol Pharmacol. 1994; 46:901-908 18. Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, Tuder RM. Modern age pathology of pulmonary arterial hypertension. …

Biological response modifiers and infectious diseases: actual and potential therapeutic agents.

Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against vi

The 44th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Oral Session

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Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML).

Despite the availability of an increasing number of targeted therapeutics and wider use of allogeneic hematopoietic stem cell transplantation, many patients with acute myeloid leukemia (AML) ultimately succumb to this disease. Given their remarkable efficacy in B-acute lymphoblastic leukemia and other CD19-expressing B cell malignancies, there is hope adoptive cellular transfer, particularly chimeric antigen receptor (CAR)-modified immune effector cell (IEC) therapies, may afford a novel, potent immune-based approach for the treatment of AML that complements or replaces existing ones and impro

Outcomes of patients with hematological malignancies complicated with autoimmune diseases after allogeneic hematopoietic stem cell transplantation: A ten-year real-world study.

BACKGROUND AND OBJECTIVES: Patients with autoimmune diseases (ADs) are at an increased risk of developing hematological malignancies (HMs). While allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for HMs, the outcomes in patients with concomitant ADs and the effects of transplantation on autoimmune conditions remain poorly characterized. METHODS: In this real-world study, we compared transplantation outcomes between 41 patients with HMs and preexisting ADs and 123 matched controls with HMs but without ADs. RESULTS: A total of 65.8% of the patients with ADs h

Ruxolitinib for the treatment of acute graft-versus-host disease: a retrospective analysis.

Steroid-refractory acute graft-versus-host disease (aGvHD) is a serious complication after allogeneic hematopoietic stem cell transplantation, associated with significant mortality. Ruxolitinib was the first drug approved for aGvHD, based on results of the REACH2 trial; however, real-world data are limited. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of aGvHD at our center from March 2016 to August 2022 and assessed biomarkers of risk. We identified 49 patients receiving ruxolitinib as second- (33/49), third- (11/49), fourth- (3/49), or fifth-line (2/49) tr

Controversies about immunoglobulin replacement therapy in HSCT recipients with hypogammaglobulinemia.

The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experie

Exercise before, during, and after Hospitalization for Allogeneic Hematological Stem Cell Transplant: A Feasibility Randomized Controlled Trial.

People with cancer who undergo allogeneic hematological stem cell transplant (allo-HSCT) experience significant deconditioning that can compromise quality of life. Exercise has shown to be beneficial before or after allo-HSCT; however, little is known about exercise therapy delivered across the continuum of care. We conducted a feasibility randomized controlled trial of exercise delivered prior to admission, during the inpatient stay, and after discharge versus control in people with planned allo-HSCT. Feasibility was assessed via recruitment and retention rates, the incidence of adverse event