Safety and Efficacy of CD123-Targeted CAR-T Therapy for Relapsed/Refractory Acute Myeloid Leukemia

Conditions:   Leukemia;   Leukemia, Myeloid;   Leukemia, Myeloid, Acute Intervention:   Biological: CD123 CAR-T cells Sponsor:   Chongqing Precision Biotech Co., Ltd Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials

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OBJECTIVES: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used. METHODS: We conducted a retrospective comparison of “ MEC ” (mitoxantrone, etoposide, and cytarabine) and “ FLAG-IDA ” (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML. RESULTS: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) ...
Source: Clinics - Category: General Medicine Source Type: research
Contributors : Hiroshi Ureshino ; Yuki Kurahashi ; Tatsuro Watanabe ; Satoshi Yamashita ; Kazuharu Kamachi ; Yuki Fukuda-Kurahashi ; Nao Yoshida ; Naoko Hattori ; Yoshihiro Hayashi ; Kaoru Tohyama ; Seiji Okada ; Hironori Harada ; Toshikazu Ushijima ; Shinya KimuraSeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensDNA methyltransferase inhibitors have improved the prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). However, these agents must be administered intravenously or subcutaneously because they are degraded easily by cytidine deaminase (CDA). OR2100 (OR21), an...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by genome tiling array Homo sapiens Source Type: research
This study was designed to investigate the interactions between human FLT3 in the kinase domain with several indolin−2-one derivatives, structurally similar to Sunitinib. Molegro Virtual Docker (MVD) software was utilized in docking analyses. The predicted model of the training group, considering nineteen amino acid residues, performed in Chemoface, achieved an R2 of 0.82, suggesting that the binding conformations of the ligands with FLT3 are reasonable, and the data can be used to predict the interaction energy of other FLT3 inhibitors with similar molecular patterns. The MolDock Score for energy for compound 1 ...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
AbstractExpression of Epidermal Growth Factor Receptor (EGFR), an important proto-oncogene, regulates cell differentiation, proliferation, cell migration and survival in most of the cancer types.EGFR expression has been reported in Acute Myeloid Leukaemia (AML), however, many other reports nullifiedEGFR expression in AML. These contradictory data prompted us to reevaluate the expression ofEGFR in AML and carry out a comparative survival analysis betweenEGFR expressing and non-expressing AML patients (Children and Acute Promyelocytic Leukaemia patients excluded). Bone marrow and/or peripheral blood samples were collected fr...
Source: Indian Journal of Hematology and Blood Transfusion - Category: Hematology Source Type: research
Authors: Hilal T Abstract The use of small molecule inhibitors in acute myeloid leukaemia (AML) has become ubiquitous with the US Food and Drug Administration approval of multiple agents between 2017 and 2018. Despite the promise, some of these indications are based on early efficacy data (phase I/II), and single-arm studies, and have not been tested in randomised trials. Furthermore, there are important limitations in the evidence that exists in randomised trials. This perspective aims to summarise the data that formed the basis for approval of gilteritinib, glasdegib, ivosidenib, enasidenib and venetoclax. It als...
Source: Ecancermedicalscience - Category: Cancer & Oncology Tags: Ecancermedicalscience Source Type: research
We present two cases of angioimmunoblastic T-cell lymphoma (AITL) and one case of T-cell acute lymphoblastic leukaemia (T-ALL) that developed in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively. All malignancies were advanced at diagnosis and exhibited disease progression, regardless of the mutational status of the underlying ET/PMF, presence of cytogenetic abnormalities, type of T-cell neoplasm or systemic chemotherapy utilised. The median time to diagnosis of AITL or T-ALL from the onset of MPN was 4.5 years (range: 6 months-10 years). This single institutional case series demons...
Source: Ecancermedicalscience - Category: Cancer & Oncology Tags: Ecancermedicalscience Source Type: research
Authors: Shallis RM, Stahl M, Bewersdorf JP, Hendrickson JE, Zeidan AM Abstract Introduction: Hyperleukocytosis, defined as a total white blood cell count (WBC)>50 or more commonly>100 x 109 cells/L, is a presenting feature of acute myeloid leukemia (AML) in about 6-20% of cases and is associated with a higher risk of tumor lysis syndrome (TLS), disseminated intravascular coagulation (DIC), clinical leukostasis with end organ damage, and mortality.Areas Covered: In this review authors discuss the implications of hyperleukocytosis in AML and the current understanding of cytoreductive strategies with a focus on...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Most patients with acute myeloid leukemia (AML) die from complications arising from cytopenias resulting from bone marrow (BM) failure. The common presumption among physicians is that AML-induced BM failure is primarily due to overcrowding, yet BM failure is observed even with low burden of disease. Here, we use large clinical datasets to show the lack of correlation between BM blast burden and degree of cytopenias at the time of diagnosis. We develop a splenectomized xenograft model to demonstrate that transplantation of human primary AML into immunocompromised mice recapitulates the human disease course by induction of B...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
Neurolysin (NLN) is a zinc metallopeptidase whose mitochondrial function is unclear. We found that NLN was overexpressed in almost half of patients with acute myeloid leukemia (AML), and inhibition of NLN was selectively cytotoxic to AML cells and stem cells while sparing normal hematopoietic cells. Mechanistically, NLN interacted with the mitochondrial respiratory chain. Genetic and chemical inhibition of NLN impaired oxidative metabolism and disrupted the formation of respiratory chain supercomplexes (RCS). Furthermore, NLN interacted with the known RCS regulator, LETM1, and inhibition of NLN disrupted LETM1 complex form...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
olo Estrogen receptor (ER) signaling has been widely studied in a variety of solid tumors, where the differential expression of ERα and ERβ subtypes can impact prognosis. ER signaling has only recently emerged as a target of interest in acute myeloid leukemia (AML), an aggressive hematological malignancy with sub-optimal therapeutic options and poor clinical outcomes. In a variety of tumors, ERα activation has proliferative effects, while ERβ targeting results in cell senescence or death. Aberrant ER expression and hypermethylation have been characterized in AML, making ER targetin...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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