Relapsed disease: off-the-shelf immunotherapies vs customized engineered products

Innovations in immuno-oncology for lymphomas have outpaced therapeutic developments in any other cancer histology. In the 1990s, rituximab, a CD20 monoclonal antibody, drastically changed treatment paradigms for B-cell non-Hodgkin lymphomas (B-NHLs). In parallel, the concept that T cells could be genetically reprogrammed and regulated to address tumor cell evasion was developed. Twenty years later, this concept has materialized—3 customized engineered CD19 chimeric antigen receptor T-cell (CART) constructs have been embraced as third-line therapies and beyond for aggressive B-NHL. Responses with CARTs are durable in 30% to 40% of patients, with consistent results in older patients, primary refractory disease, high-grade B-cell lymphoma, and patients with concurrent secondary central nervous system disease, all features historically associated with poorer outcomes. Challenges associated with the administration of CARTs include cumbersome and time-consuming manufacturing processes, toxicities, and cost, not to mention a substantial risk of relapse. Fortunately, as our understanding of how to manipulate the immune system to achieve full antitumor potential has grown, so has the rapid development of off-the-shelf immunotherapies, with CD20/CD3 bispecific antibodies standing out above all others. These agents have shown promising activity in aggressive B-NHL and have the potential to circumvent some of the challenges encountered with customized engineered products. However, toxicities remain substantial, dosing schedules intensive, and experience limited with these agents. Novel customized and off-the-shelf therapeutics as well as rational combinations of these agents are underway. Ultimately, growing experience with both customized engineered and off-the-shelf immunotherapies will provide guidance on optimal methods of delivery and sequencing.

Cerebral lesions in hematological malignancies: a case report

Background Progressive multifocal leukoencephalopathy is a rare central nervous system disease, resulting from reactivation of latent John Cunningham virus. Monoclonal antibodies have recently become a relevant risk factor for developing progressive multifocal leukoencephalopathy. Case summary We report the case of a 62-year-old Caucasian man who was admitted to our department in June 2020 because of right homonymous hemianopia. Magnetic resonance imaging findings were first interpreted as an intracranial relapsed lymphoma, so brain biopsy was performed, but no neoplastic cell was found. Histological sample only showed a large number of macrophages. The patient came back to our attention because of the worsening of neurological symptoms. A second magnetic resonance imaging showed widespread lesions suggestive of a demyelinating process. John Cunningham virus DNA was detected by polymerase chain reaction assay of the cerebrospinal fluid (over 9 million units/μL). The patient was treated supportively, but the outcome was poor. Discussion A multidisciplinary assessment should be performed for differential diagnosis of cerebral lesions in hematologic malignancies. Progressive multifocal leukoencephalopathy should be suspected in cases of subacute neurological symptoms and imaging findings consistent with it, especially if the patient received immunosuppressive or immunomodulatory drugs.

Emerging evolution trends of application of natural products in Alzheimer’s disease

The main objective of this review was to explore the research foci and emerging trends of application of natural products in AD from 1990 to 2019 and evaluated publications qualitatively and quantitatively. CiteSpace V. 4.0 was used to identify top authors, journals, institutions, countries, keywords, co-cited articles, and trends and obtain the visual knowledge maps. Results revealed that the USA, People’s Republic of China and India were the major research countries in this field, while the Western Europe and North America were the areas with frequent international cooperation. Moreover, there was a close collaboration between universities and research institutes. The J Alzheimers Dis was the most productive journal. Alzheimers disease, natural product, brain, central nervous system, disease, and oxidative stress are some of the high centrality and high frequency keywords in the co-occurrence analysis; Indicating Alzheimers disease and its pathogenesis and natural product remain the hotspots in the field. This paper provides an insight into the application of natural products in AD, and provides useful information for AD researchers to find potential collaborators and cooperative institutions.

The Clinical Contribution of Full-Field Electroretinography and 8-Year Experiences of Application in a Tertiary Medical Center

Electroretinography (ERG) is an important and well-established examination for retinal and visual pathway diseases. This study reviewed the medical records of patients who received full-field ERG (ffERG) at a single medical center between 2012 and 2019, which was an 8-year experience in the clinical contribution of ERG. Based on the indication for scheduling ffERG and the final diagnosis, patients could be classified into six groups: ‘retinal dystrophies’, ‘other retinal or macular diseases’, ‘optic neuropathies’, ‘visual complaints’, ‘systemic diseases’, and ‘others’. A total of 1921 full-field electroretinograms (ffERGs) (1655 patients) were included. The average number of ffERGs performed per year was 262 and the number of annual ffERGs was constant. The ‘retinal dystrophies’ group accounted for 36.5% of the studied population, followed by the ‘other retinal or macular diseases’ group (20.2%). The most common systemic disease was central nervous system disease. The rates of abnormal ffERGs in the ‘systemic diseases’, ‘optic neuropathies’, and ‘visual complaints’ groups were 27.3%, 22.6%, and 10.1%, respectively (p < 0.001). Higher rates were found in patients <20 years old in the ‘systemic diseases’ and ‘optic neuropathies’ groups; epilepsy and optic nerve atrophy were the most common diagnoses, respectively. In brief, by quantifying the functional response in the retina, ffERG is indispensable for diagnosis and prognosis in ophthalmologic and multidisciplinary practice.

What Can We Learn from Sex Differences in MS?

Multiple sclerosis (MS) is the major acquired central nervous system disease of young adults. It is a female predominant disease. Multiple aspects of MS are influenced by sex-based differences. This has become an important area of research and study. It teaches us how the impact of sex on a disease can lead to new insights, guidelines, management, and treatments.

A Natural History Study of Nitrous Oxide versus Propofol-Assisted Intrathecal Therapy in the Treatment of Acute Lymphoblastic Leukemia

Background: Childhood acute lymphoblastic leukemia (ALL) treatment requires numerous lumbar punctures (LPs) with intrathecal (IT) chemotherapy to prevent and treat central nervous system disease. Historically, LPs in this setting are performed using propofol sedation. At our institution, LPs are often alternatively performed under nitrous oxide (N2O). To date, there have been no large scale assessments comparing these sedation methods for this purpose. Procedures: Retrospective cohort study of patients aged 0-31 years with ALL treated between 1/1/2013-12/31/2018 at the Children’s Minnesota Cancer and Blood Disorders Center, including all therapeutic LPs performed in the clinic setting under either propofol or N2O. Results: Among 215 patients and 2677 therapeutic LPs, 56.6% (n = 1515) occurred under N2O with 43.3% (n = 93) of patients using exclusively N2O with all LPs. The incidence of traumatic LPs (RBC ≥ 10 cells/µL) were similar between both treatments (27.3% vs 30.2). Successful IT chemotherapy delivery (99.7% N2O vs 99.8% propofol) did not differ between sedation types. Experiencing a traumatic LP under N2O was associated with a sedation switch for the subsequent LP (aOR 2.40, p=0.002) while older age (aOR 1.08, p<0.0001) and higher BMI percentile (aOR 1.01, p=0.009) were associated with increased likelihood for undergoing a traumatic LP. Conclusion: N2O is an effective sedation option for therapeutic LPs in children with ALL with noninferiority to propofol in terms of IT chemotherapy administration and traumatic LP incidence. For many patients, N2O can effectively replace propofol during LP procedures, which has important safety and quality-of-life implications.