Case Report: Transformation of natural killer-cell large granular lymphocytic leukemia to aggressive natural killer cell leukemia

Large Granular Lymphocytic Leukemia (LGLL) is a rare clonal proliferative disorder of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, characterized by persistent expansion of large granular lymphocytes (LGLs) in peripheral blood for over six months. According to the 2022 World Health Organization (WHO) classification, LGLL is categorized into T-LGLL, NK-large granular lymphocytic leukemia (NK-LGLL). Aggressive natural killer cell leukemia (ANKL), as a Mature T-cell and NK-cell leukemia independent of LGLL, also has morphologic characteristics of large granular lymphocytes. This report describes a rare case of NK-LGLL transforming into ANKL. This case highlights the necessity of differential diagnosis in LGLL and suggests that proteasome inhibitors combined with immune checkpoint inhibitors may represent a promising therapeutic strategy for ANKL

Case report: Successful management of a refractory double-expressor diffuse large B-cell lymphoma patient under the guidance of in vitro high-throughput drug sensitivity test

IntroductionDouble-expressor diffuse large B-cell lymphoma (DEL), harboring double expression of MYC and BCL2, has an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). We initiated a clinical trial to treat newly diagnosed DEL with R-CHOP plus Bruton’s tyrosine kinase (BTK) inhibitor (BTKi) zanubrutinib (ZR-CHOP) and achieved a high complete response (CR) rate while four patients progressed during therapy, one of them carrying ATM and CD58 mutations. We applied an in vitro high-throughput drug sensitivity test for the prediction of clinical responses to different drugs in this patient.Case presentationWe report a 30-year-old female patient diagnosed with stage III (DEL), with ATM and CD58 mutations. The patient achieved partial response (PR) after two cycles of ZR-CHOP and remained PR after four cycles of ZR-CHOP, while the disease progressed after six cycles of ZR-CHOP. High-throughput drug screening using a panel of 117 compounds identified a range of therapies with efficacy for this patient. The primary tumor cells showed moderate sensitivity to bortezomib, thalidomide, and gemcitabine as a single agent and bortezomib, thalidomide, and dexamethasone (VTD) as a combined regimen. The patient was treated with two cycles of VTD regimen (bortezomib 1.3 mg/m2, d1, 4, 8, 11; thalidomide 100 mg, d1-21; dexamethasone 20 mg, d1, 2, 4, 5, 8, 9) and achieved PR with only a small lesion left. Another two cycles of VTD plus gemcitabine were then administered, and the patient achieved CR. Stem cells were mobilized, and autologous hematopoietic stem cell transplantation was carried out afterward. The patient remained CR for more than 3 months after transplantation.ConclusionIn this article, we present a first-line chemoresistant DEL patient with ATM and CD58 mutations who was treated successfully with VTD plus gemcitabine under the guidance of in vitro high-throughput drug sensitivity test

A Smartphone Based in-Gel Loop Mediated Isothermal Amplification (gLAMP) System Enables Rapid Coliphage MS2 Quantification in Environmental Waters

Model coliphages (e.g., ΦX174, MS2, and PRD1) have been widely used as surrogates to study the fate and transport of pathogenic viruses in the environment and during wastewater treatment. Two groups of coliphages (F-specific and somatic) are being explored as indicators of viral fecal pollution in ambient water. However, the detection and quantification of coliphages still largely rely on time-consuming culture-based plaque assays. In this study, we developed an in-gel loop-mediated isothermal amplification (gLAMP) system enabling coliphage MS2 quantification within 30 min using standard laboratory devices. Viral particles (MS2) were immobilized with LAMP reagents in polyethylene glycol hydrogel, and then viral RNAs were amplified through a LAMP reaction. Due to the restriction effect of the hydrogel matrix, one viral particle would only produce one amplicon dot. Therefore, the sample virus concentrations can be determined based on the number of fluorescent amplicon dots using a smartphone for imaging. The method was validated by using artificially spiked and naturally contaminated water samples. gLAMP results were shown to correlate well with plaque assay counts (R^2 = 0.984, p < 0.05) and achieved similar sensitivity to quantitative reverse-transcription polymerase chain reaction (RT-qPCR; 1 plaque-forming unit per reaction). Moreover, gLAMP demonstrated a high level of tolerance against inhibitors naturally present in wastewater, in which RT-qPCR was completely inhibited. Besides MS2, gLAMP can also be used for the quantification of other microbial targets (e.g., Escherichia coli and Salmonella). Considering its simplicity, sensitivity, rapidity, and versatility, gLAMP holds great potential for microbial water-quality analysis, especially in resource-limited settings

Case report: Bridging radiation therapy before chimeric antigen receptor T-cell therapy induces sustained remission in patients with relapsed/refractory double-expressor diffuse large B-cell lymphoma with localized compressive symptoms

BackgroundHigh-risk double-expressor diffuse large B-cell lymphoma has an inferior prognosis following standard first-line therapy. After failure of second-line therapy, treatment options are limited if accompanied by localized compressive symptoms. Chimeric Antigen Receptor T cell (CAR-T) therapy preceded by bridging radiotherapy may be an effective emerging therapy.Case presentationWe report a 66-year-old female patient diagnosed with stage IV double-expressor diffuse large B-cell lymphoma. The patient achieved progressive disease after two cycles of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone and continued to develop cervical lymph node recurrence after second-line therapy. The patient was infused with CAR-T cells after receiving focal bridging radiotherapy and remained in complete response more than 9 months after treatment. In addition, the patients did not experience serious adverse reactions related to radiotherapy as well as CAR-T cell therapy.ConclusionsIn this article, we describe a patient with double-expressor diffuse large B-cell lymphoma with localized compression symptoms after second-line treatment failure who benefited from CAR-T combined with focal bridging radiotherapy

Bispecific antibodies in immunotherapy for acute leukemia: latest updates from the 66th annual meeting of the American society of hematology, 2024

Bispecific antibodies (BsAbs) are cutting-edge immunotherapy agents that can bind two distinct antigens or epitopes simultaneously. They hold significant potential in targeting leukemic cell markers and activating immune cells like T cells or NK cells to eliminate malignant cells. BsAb treatments showed encouraging outcomes for both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In relapsed/refractory (R/R) ALL, BsAbs improved overall survival (OS) and achieved measurable residual disease (MRD) negativity in most patients. Blinatumomab plus standard chemotherapy or in combination with other treatments, such as Mini-Hyper-CVD and Inotuzumab Ozogamicin, improved disease-free survival (DFS) in B-ALL. In AML and related conditions, novel BsAbs like AFM28 (CD123xCD16A) and Vibecotamab (CD123xCD3) showed promising efficacy in heavily pretreated R/R AML and in MDS/CMML following the failure of treatment with hypomethylating agents (HMA). The meeting underscored the transformative potential of BsAbs, especially in ALL-focused trials, with ongoing research aiming to evaluate their safety and efficacy in broader patient populations and combination regimens. This summary highlights the latest progress in BsAb-based immunotherapy presented at the ASH 2024 meeting, held from December 7–10 in San Diego, California

Tracing the history of clinical practice of liquid biopsy: a bibliometric analysis

IntroductionLiquid biopsy holds great promise in clinical diagnosis, treatment, and prognostic monitoring. This study reveals the development of liquid biopsy in clinical practice through a comprehensive bibliometric analysis.MethodsA total of 40 years of research literature in this field was included from the Web of Science Core Collection (WoSCC), analyzing the evolving research trends of liquid biopsy in clinical practice. We constructed co-occurrence networks for countries, institutions, authors, and keywords, integrating citation analysis and journal impact metrics to provide a comprehensive view of the research landscape in the field of liquid biopsy.ResultsThe results show a significant growth trend in the clinical practice of liquid biopsy, with China and the United States being the leading contributors. Institutions such as Harvard University and the University of California system play a central role in the global collaboration network. Cancers has become the primary publication outlet for the field, while highly cited journals like Clinical Cancer Research play a crucial role in advancing its development. Keyword analysis reveals that research has progressively expanded into clinical applications, personalized treatment, and prognostic evaluation.DiscussionOverall, as technology and applications continue to mature, liquid biopsy is expected to play an even greater role in the early diagnosis, treatment evaluation, and personalized treatment of cancer and other diseases

The Beam Screening Device for the Production of Radioisotopes Based on 100 MeV High-Flow Proton Cyclotron

In some radioisotope production experiments，100 MeV high-current proton cyclotron is required to extract a single-turn beam to meet the experimental requirements，but at present，there is a serious problem of turn overlap when the beam is extracted，and a beam screening device needs to be designed to improve the quality of the drawn beam. The beam screening device has a frame structure and slit motion system based on the cyclotron，and a control system based on PLC design to control the stepper motor and use the electronic ruler and PID control algorithm to achieve closed-loop control. After many times of operation and debugging，the motion accuracy of the mechanical device is ±0.2 mm，and the beam screening can be realized during the operation of the accelerator，which has reference significance for the design and manufacture of the cyclotron beam screening device

Prognostic risk factors of pneumonia associated with COVID-19 in patients with lymphoma

ObjectivePatients with hematological malignancies have an elevated risk of developing pneumonia after contracting COVID-19. Lymphoma is the most prevalent hematologic malignancy. It is critical to identify patients at high risk of contracting COVID-19-associated pneumonia.MethodsFrom January 11–31, 2023, we distributed questionnaires to patients diagnosed with lymphoma according to 2016 World Health Organization diagnostic and classification criteria. COVID-19 infection was confirmed based on symptoms and laboratory tests. Pneumonia was confirmed using computed tomography scans.ResultsIn total, 257 patients were included in this study; 221 patients (86.0%) had COVID-19 infection and 61 (27.6%) of these had pneumonia. Patients with B-cell non-Hodgkin lymphoma (B-NHL) had a significantly higher pneumonia incidence than patients with other lymphoma types (31.8% vs. 27.6%, P=0.005). Higher incidence of pneumonia was observed in patients receiving anti-CD20 therapy (30.0% vs. 16.3%, P=0.048) and Bruton’s tyrosine kinase (BTK) inhibitor therapy (51.3% vs. 22.5%, P=0.001). B-NHL (hazard ratio [HR]=3.7, 95% confidence interval [CI] 1.4–10.0, P=0.009), anti-CD20 therapy (HR=2.3, 95% CI 1.0–5.2, P=0.050), BTK inhibitor (HR=3.6, 95% CI 1.8–7.4, P&lt;0.001), active therapy (HR=3.0, 95% CI 1.5–5.7, P=0.001), and lack of disease remission (HR=3.7, 95% CI 1.8–7.4, P=0.001) were high-risk factors for developing pneumonia. Anti-PD-1 therapy was a protective factor against pneumonia development (HR=0.2, 95% CI 0.05–0.9, P=0.034). In multivariable analysis, BTK inhibitor (HR=3.5, 95% CI 1.6–8.0, P=0.003), active therapy (HR=3.3, 95% CI 1.6–6.8, P=0.001), and disease non-remission (HR=2.9, 1.3–6.4, P=0.007) were independent risk factors for pneumonia development after COVID-19 infection in patients with lymphoma.ConclusionsPatients with lymphoma receiving BTK inhibitors, undergoing active therapy, and lacking disease remission exhibited a higher risk for pneumonia associated with COVID-19