The magnetically confined semiconductor heterostructure (MCSH) is often used as the momentum filter due to an essentially 2-D process for the electronic tunneling. Taking a typical MCSH into account, ...we theoretically investigate how to manipulate such momentum filters by the δ-doping technique. The momentum-filtering efficiency can be tuned because of the δ-doping dependence of the electron transmission. The involved MCSH can be employed as a controllable momentum filter.
Recent research work on magneto-optical micro- structure devices in terahertz (THz) regime has been reviewed. Some magneto-optical materials responding at THz frequency range were introduced. Based ...on these magneto-optical materials, MO microstructures devices were reviewed, including magnetic photonic crystals, magneto-plasmonics, and magneto-metasurface all in the submillimetre scale. These devices can realize several functions of isolating, modulation, sensing, and directional beam scanning. Moreover, the necessary conditions of forming THz nonreciprocal transmission in magneto-optical microstructure devices were concluded, and the tunability of these devices was also analysed, which strongly depends on the magneto-optical property of material and the symmetry of structure. The unique magneto-optical effects make it play an irreplaceable role in the high performance THz applications of communication, imaging, and sensing systems.
The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many ...countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up.
Participants received an average dose of 0.5 × 10
cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated.
Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes.
These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma.
LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.
This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo ...naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL).
In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin.
The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the -10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups.
Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.
A magneto-metasurface with nonreciprocal terahertz (THz) transmission has been proposed to form a THz isolator. Importantly, we have discussed the two necessary conditions for THz nonreciprocal ...transmission in the metasurface: (1) There should be magneto-optical responses for THz waves in the metasurface; (2) The transmission system of the metasurface needs to be asymmetric for forward and backward waves. These two conditions lead to the time reversal symmetry breaking of system, and the magnetoplasmon mode splitting and nonreciprocal resonance enhancement can be observed in the asymmetry magneto-metasurface. Moreover, the isolation dependences and tunability on the external magnetic field and temperature have also been investigated, which shows that the best operating state with a high isolation can be designed. The numerical simulations show a maximum isolation of 43 dB and a 10 dB operating bandwidth of 20 GHz under an external magnetic field of 0.3 T, and the insertion loss is smaller than 1.79 dB. This low-loss, high isolation, easy coupling THz isolator has broadly potentials for THz application systems.
All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination-based therapy has benefitted newly diagnosed acute promyelocytic leukemia (APL) in short-term studies, but the long-term efficacy and ...safety remained unclear. From April 2001, we have followed 85 patients administrated ATRA/ATO with a median follow-up of 70 months. Eighty patients (94.1%) entered complete remission (CR). Kaplan-Meier estimates of the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 89.2% ± 3.4% and 91.7% ± 3.0%, respectively, and the 5-year relapse-free survival (RFS) and OS for patients who achieved CR (n = 80) were 94.8% ± 2.5% and 97.4% ± 1.8%, respectively. Upon ATRA/ATO, prognosis was not influenced by initial white blood cell count, distinct PML-RARα types, or FLT3 mutations. The toxicity profile was mild and reversible. No secondary carcinoma was observed, and 24 months after the last dose of ATRA/ATO, patients had urine arsenic concentrations well below the safety limit. These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.
Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients, including those with ...normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study that identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of well-established markers. We further compared the gene expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and trichloracetic acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (Ara-C), whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML.
•Acute myeloid leukemia (AML) patients present an altered glucose metabolism signature.•A panel of 6 metabolite biomarkers involved in glucose metabolism are identified with prognostic value for cytogenetically normal AML.
Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56(+) and cytoCD3(+) lymphocytes with aggressive clinical course, which is prevalent in Asian and South American populations. ...The molecular pathogenesis of NKTCL has largely remained elusive. We identified somatic gene mutations in 25 people with NKTCL by whole-exome sequencing and confirmed them in an extended validation group of 80 people by targeted sequencing. Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (21/105 subjects, 20.0%), tumor suppressors (TP53 and MGA), JAK-STAT-pathway molecules (STAT3 and STAT5B) and epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). As compared to wild-type protein, DDX3X mutants exhibited decreased RNA-unwinding activity, loss of suppressive effects on cell-cycle progression in NK cells and transcriptional activation of NF-κB and MAPK pathways. Clinically, patients with DDX3X mutations presented a poor prognosis. Our work thus contributes to the understanding of the disease mechanism of NKTCL.
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